Breast Cancer: A focus on BRCA Mutations.
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A FOCUS ON BRCA MUTATIONS IN BREAST CANCER Mohamed Abdulla M.D. Prof. of Clinical Oncology Cairo University Dubai – 11/09/2015
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Transcript of Breast Cancer: A focus on BRCA Mutations.
A FOCUS ON BRCA MUTATIONS IN BREAST CANCERMohamed Abdulla MDProf of Clinical OncologyCairo University
Dubai ndash 11092015
Speaker DisclosuresMember of Advisory Board Consultant and Speaker forbull Amgen Astellas Astra Zeneca Hoffman la Roche Janssen
Cilag Merck Serono Novartis Pfizer
Speaker Disclosures
Breast CancerThe Story
All Women
12 All Breast Cancer
Cases (100)
73Sporadic Cases ldquoNo Family Clusteringrdquo
27Familial Breast
Cancer
5 ndash 10Mutation in Single High Penetrance
Gene
asymp 20Mutations in Low
Penetrance Genes
88 No Breast Cancer
Narod SA BRCA mutations in the management of breast cancer the state of the art Nat Rev Clin Oncol 2010 7702
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Autosomal Dominant
Inheritance with High Penetrance
bull 50 Chance of Inheritance
bull Lifetime Risk of Cancer = 30-70
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Female Breast
Male Breast
Ovary Pancreas Prostate0
10
20
30
40
50
60
70
80
BRCA1BRCA2
Presented by Judy Garber at 2015 ASCO Annual Meeting
54 ndash 85
Presented By Elizabeth Swisher at 2015 ASCO Annual Meeting
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
King Science New York Breast Cancer Study 2003
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Speaker DisclosuresMember of Advisory Board Consultant and Speaker forbull Amgen Astellas Astra Zeneca Hoffman la Roche Janssen
Cilag Merck Serono Novartis Pfizer
Speaker Disclosures
Breast CancerThe Story
All Women
12 All Breast Cancer
Cases (100)
73Sporadic Cases ldquoNo Family Clusteringrdquo
27Familial Breast
Cancer
5 ndash 10Mutation in Single High Penetrance
Gene
asymp 20Mutations in Low
Penetrance Genes
88 No Breast Cancer
Narod SA BRCA mutations in the management of breast cancer the state of the art Nat Rev Clin Oncol 2010 7702
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Autosomal Dominant
Inheritance with High Penetrance
bull 50 Chance of Inheritance
bull Lifetime Risk of Cancer = 30-70
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Female Breast
Male Breast
Ovary Pancreas Prostate0
10
20
30
40
50
60
70
80
BRCA1BRCA2
Presented by Judy Garber at 2015 ASCO Annual Meeting
54 ndash 85
Presented By Elizabeth Swisher at 2015 ASCO Annual Meeting
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
King Science New York Breast Cancer Study 2003
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast CancerThe Story
All Women
12 All Breast Cancer
Cases (100)
73Sporadic Cases ldquoNo Family Clusteringrdquo
27Familial Breast
Cancer
5 ndash 10Mutation in Single High Penetrance
Gene
asymp 20Mutations in Low
Penetrance Genes
88 No Breast Cancer
Narod SA BRCA mutations in the management of breast cancer the state of the art Nat Rev Clin Oncol 2010 7702
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Autosomal Dominant
Inheritance with High Penetrance
bull 50 Chance of Inheritance
bull Lifetime Risk of Cancer = 30-70
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Female Breast
Male Breast
Ovary Pancreas Prostate0
10
20
30
40
50
60
70
80
BRCA1BRCA2
Presented by Judy Garber at 2015 ASCO Annual Meeting
54 ndash 85
Presented By Elizabeth Swisher at 2015 ASCO Annual Meeting
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
King Science New York Breast Cancer Study 2003
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Autosomal Dominant
Inheritance with High Penetrance
bull 50 Chance of Inheritance
bull Lifetime Risk of Cancer = 30-70
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Female Breast
Male Breast
Ovary Pancreas Prostate0
10
20
30
40
50
60
70
80
BRCA1BRCA2
Presented by Judy Garber at 2015 ASCO Annual Meeting
54 ndash 85
Presented By Elizabeth Swisher at 2015 ASCO Annual Meeting
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
King Science New York Breast Cancer Study 2003
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
Female Breast
Male Breast
Ovary Pancreas Prostate0
10
20
30
40
50
60
70
80
BRCA1BRCA2
Presented by Judy Garber at 2015 ASCO Annual Meeting
54 ndash 85
Presented By Elizabeth Swisher at 2015 ASCO Annual Meeting
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
King Science New York Breast Cancer Study 2003
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Presented By Elizabeth Swisher at 2015 ASCO Annual Meeting
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
King Science New York Breast Cancer Study 2003
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast cancer by
Age 50
Breast Cancer by
Age 70
2nd Breast Cancer by
Age 70
0
50
100
28 11
50
87
64
General PopulationBRCA Mutation
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Claus EB et al The genetic attributable risk of breast and ovarian cancer Cancer 1996772318-2324
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
Adapted from Clemons M Goss P Estrogen and the risk of breast cancer N Engl J Med 2001 344276
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA GenesBasic Knowledge
Eukaryotic Genome
Constant StressEndogenous Exogenous
Continuous Damage
Continuous Repair
Misrepair Perfect Repair No Repair
Mutations Apoptosis
Tumor Suppressor Genes
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
BRCA1 amp BRCA2
bull DNA Repairbull Control of Cell Cycle Checkpointsbull Control of Mitotic Activity
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA GenesBasic Knowledge
DNA Repair
NHEJR HR
1 2 1 2
Peter JOrsquoDonovan and David MLivingston1113088 Carcinogenesis vol31 no6 pp961ndash967 2010
G0 G1Early S
Late S G2
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Mutated Non - Mutated
P
2 Year 964 9930025 Year 853 959
10 Year 719 872
Robson M et al J Natl Cancer Inst 199991(24)2112-2117
BRCA-Associated Breast Cancer Ipsilateral amp Contralateral Recurrences
Breast Cancer with BRCA MutationsPoor Prognosis
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationsPoor Prognosis
1 Early onset of disease more years of lost life2 High prevalence of poorly differentiated high grade
and highly proliferative lesions more common in BRCA1 mutation cases
3 Higher prevalence of HR ndashve and TNBC 4 Altered sensitivity to systemic agents
bull to platinum and PARP inhibitorsbull to taxanes
5 Chemotherapy for early small tumors might improve the outcome
Rijnsburger et al JCO 2010285265Lee et al Breast Cancer Res Treat 2010 12211Hemel amp Domchek Hematol Oncol Clin North Am 2010 24799
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA Gene MutationsWho Should Be Investigated for Mutations
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA Genes MutationConfirmed Detection
Actions Taken
Cancer Surveillance
Reducing Risk
Therapeutic Implications
1 Breast Self Examination2 Breast Clinical Examination3 MammographyMRI
1 Surgical Intervention2 Chemoprevention
1 Different Disease Entity2 Locoregional Treatment3 Systemic Therapy (PARP)
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA MutationCancer Surveillance1 Breast Self-Examination Monthly at age of 18 years2 Clinical Breast Examination 2 ndash 4 times annually at
age of 25 years3 MRI ndash Breast 2 times annually (25 ndash 30 Years)4 Alternating MammographyMRI ndash Breast annually
after the age of 30
Age Mammography MRI Mammo + MRISens Spec Sens Spec Sense Spec
All Ages 396 936 853 847 934 803
lt 50 40 93 857 835 932 787
gt 50 391 959 844 885 941 853
Warner et al Ann Intern Med 2008148671Xi PA et al J Clin Oncol 201533349-56
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA MutationReducing Risk Surgical Intervention
Bilateral Prophylactic Mastectomybull 90 risk reductionbull Total gt SC mastectomybull Skin sparing +-
preservation of nippleareola complex Better cosmoses
bull Immediate reconstruction
Bilateral Salpingo-oophorectomy 77 risk reduction of all cause breast cancer mortality to age of 70 years
Ingham SL et al Risk-reducing surgery increases survival in BRCA12 mutation carriers unaffected at time of family referral Breast Cancer Res Treat 2013 142611
Finch AP et al Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol 2014 321547
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA MutationReducing Risk Chemopreventionbull Tamoxifen (5 Years) 50 of breast cancer in women
with moderately increased risk1 gt 60 years2 gt 35 years with LCIS3 166 increased risk (Gail Method)
bull NSABP (P-1) TAM 62 breast cancer risk (BRCA2)bull Role of Raloxifen and AIbull Chemoprevention lt Prophylactic Surgery
No HBOC
Eisen A Weber BL Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and controversy N Engl J Med 2001 345207Gronwald J Tung N Foulkes WD et al Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers an update Int J Cancer 2006 1182281
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
BRCA MutationReducing Risk Clinical Decision Making
Life Expectancy Quality of Life
30 years + BRCA12
Prophylactic Mastectomy 3 ndash 5 years gain
Oophorectomy 03 ndash 2 years gain
Schrag D et alN Engl J Med 1997 3361465
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
bull 655 Patientsbull Stage I - IIIbull BRCA12
Mutation
302 Patients BCT
353 Patients MRM
Failuresbull Localbull Regionalbull Systemic
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398 5 - Year 10 - Year 15 - Year 20 Year
00
50
100
150
200
250
300
350
41
105
235
302
1435
55 55
Cumulative incidence estimates for local failure as first failure by type of local treatment
BCTMRM
Cum
ulat
ive
Inci
denc
e P = lt 00001
LR = 30LF = 70
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
79
165
437
532
2681 107 107
Cumulative incidence estimates for local failure as first failure for patients choosing breast conservation by use of
adjuvant chemotherapy
BCTBCT + Cth
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 00001
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
5 - Year 10 - Year 15 - Year 20 - Year00
100
200
300
400
500
600
114
245
414
532
112
316
476
568
Cumulative incidence estimates of contralateral breast cancer by use of adjuvant radiotherapy
No RTHRTH
Cum
ulat
ive
Inci
denc
eBreast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
P = lt 044
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Conclusionsbull LR BCT gt MRM (Significant)bull Local Control BCT + CTH = MRMbull Distant Failure DSS OAS No Differencebull CBC Significantly High Irrespective of RTH Use
Prophylaxis
Breast Cancer with BRCA MutationChoice of Loco-Regional Management
Pierce et al Breast Cancer Res Treat 2010 June 121(2) 389ndash398
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Breast Cancer with BRCA MutationContralateral Breast
Int J Cancer136668-677(2015)
Number583 BRCA Mutated PBC
PHRCRRM Surveillance 242 (42) 341 (58)
Contralateral Breast Cancer
4 (2) 64 (19) P = 0001
Mortality1000 Persons - Years of Observation
96 216 HR = 049
Med
ian
Follo
w u
p =
112
yea
rs
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Take Home Messagebull Hereditary breast cancer is a unique disease with TN and HR
ndash phenotypes in gt 70 of cases and poor prognosis in vast majority of patients with compromised survival outcome
bull Deleterious BRCA mutations are associated with high risk of developing breast cancer with higher rates of local and contralateral failures than sporadic cases
bull Genetic counseling should be offered for high risk populationbull Screening mammography and MRI are complementarybull Prophylactic Bilateral Mastectomy 90 risk reductionbull Platinum compounds are key players in managementbull PARP inhibitors carry a promising change of disease
landscape
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
Thank You
- A Focus on Brca mutations in breast cancer
- Speaker Disclosures
- Breast Cancer The Story
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2
- Cancer Risk in Carriers of Germ Line Mutations in BRCA1 amp BRCA2 (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (2)
- Risk of Breast Cancer for Women with BRCA1 amp 2 Mutations (3)
- BRCA Genes Basic Knowledge
- BRCA Genes Basic Knowledge (2)
- Breast Cancer with BRCA Mutations Poor Prognosis
- Breast Cancer with BRCA Mutations Poor Prognosis (2)
- BRCA Gene Mutations Who Should Be Investigated for Mutations
- BRCA Gene Mutations Who Should Be Investigated for Mutations (2)
- BRCA Genes Mutation Confirmed Detection
- BRCA Mutation Cancer Surveillance
- BRCA Mutation Reducing Risk Surgical Intervention
- BRCA Mutation Reducing Risk Chemoprevention
- BRCA Mutation Reducing Risk Clinical Decision Making
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (2)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (3)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (4)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (5)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (6)
- Breast Cancer with BRCA Mutation Choice of Loco-Regional Manag (7)
- Breast Cancer with BRCA Mutation Contralateral Breast
- Breast Cancer with BRCA Mutation Contralateral Breast (2)
- Take Home Message
- Slide 37
-
