Author: Vincent M. Cimmino, M.D., 2011

License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution – Share Alike 3.0 License: http://creativecommons.org/licenses/by-sa/3.0/

We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material.

Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content.

For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.

Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition.

Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.

Citation Keyfor more information see: http://open.umich.edu/wiki/CitationPolicy

Use + Share + Adapt

Make Your Own Assessment

Creative Commons – Attribution License

Creative Commons – Attribution Share Alike License

Creative Commons – Attribution Noncommercial License

Creative Commons – Attribution Noncommercial Share Alike License

GNU – Free Documentation License

Creative Commons – Zero Waiver

Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ

Public Domain – Expired: Works that are no longer protected due to an expired copyright term.

Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105)

Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain.

Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ

Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair.

To use this content you should do your own independent analysis to determine whether or not your use will be Fair.

{ Content the copyright holder, author, or law permits you to use, share and adapt. }

{ Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. }

{ Content Open.Michigan has used under a Fair Use determination. }

Your Patient Has Breast Cancer Until You Prove She Doesn’t

M2 - Reproduction Sequence M2 - Reproduction Sequence Vincent M. Cimmino, MDVincent M. Cimmino, MD

Clinical Professor of SurgeryClinical Professor of Surgery University of MichiganUniversity of Michigan

Division of Surgical OncologyDivision of Surgical OncologyWinter, 2011

The patient is a 25 year old The patient is a 25 year old female with a mass in the female with a mass in the

lower inner quadrant of the lower inner quadrant of the right breast.right breast.

FibroadenomaFibroadenoma

• Most common breast neoplasm in Most common breast neoplasm in adolescents and young adult women.adolescents and young adult women.

• Usually presents as a solitary, painless, Usually presents as a solitary, painless, well-circumscribed, mobile mass.well-circumscribed, mobile mass.

• 25% are multiple.25% are multiple.

• More common in African-Americans than More common in African-Americans than Caucasians.Caucasians.

Source Undetermined

Source Undetermined

The patient is a 37 year old The patient is a 37 year old female complaining of pain female complaining of pain

in both breasts but more in both breasts but more pronounced prior to the pronounced prior to the

beginning of her menses.beginning of her menses.

Fibrocystic ChangesFibrocystic Changes

• Affect 30% to 35% of women between ages of 20 and Affect 30% to 35% of women between ages of 20 and 40 years.40 years.

• Usually multifocal and bilateral.Usually multifocal and bilateral.• Most common complaint is premenstrual swelling and Most common complaint is premenstrual swelling and

tenderness.tenderness.• Symptoms gradually disappear after menopause.Symptoms gradually disappear after menopause.• Not associated with an increased risk for cancer unless Not associated with an increased risk for cancer unless

lobular or ductal atypical hyperplasia involved.lobular or ductal atypical hyperplasia involved.• Treatment involves use of NSAIDS, oral contraceptives, Treatment involves use of NSAIDS, oral contraceptives,

evening primrose oil or yam cream.evening primrose oil or yam cream.

1-21-05

Source Undetermined

2-1-05

Source Undetermined

Source Undetermined

A 35 year old Caucasian A 35 year old Caucasian female comes to your office female comes to your office and states that she has had a and states that she has had a

nipple discharge on the left for nipple discharge on the left for three months.three months.

Intraductal PapillomaIntraductal Papilloma

• Benign local proliferation of ductal Benign local proliferation of ductal epithelial cells.epithelial cells.

• Unilateral serosanguinous or bloody Unilateral serosanguinous or bloody nipple discharge.nipple discharge.

• Treatment: Treatment: • DuctogramDuctogram• DuctoscopyDuctoscopy• Excise affected ductExcise affected duct

Ductogram: dilated duct with intralumenal filling defect.

Source Undetermined

Source Undetermined

A 40 year old female strong history A 40 year old female strong history of fibrocystic breast disease comes of fibrocystic breast disease comes to your office and states that she to your office and states that she

had a mammogram done two weeks had a mammogram done two weeks ago which showed a suspicious ago which showed a suspicious

lesion in her right breast.lesion in her right breast.

ALND ControversyALND Controversy

• To do or not to doTo do or not to do

• Er+ Pr+ H2N-Er+ Pr+ H2N-

• T1 and T2 tumorsT1 and T2 tumors

• Sentinel lymph node positiveSentinel lymph node positive

• Patients to undergo radiation and/or Patients to undergo radiation and/or chemotherapychemotherapy

• Volume of metastasis in lymph nodeVolume of metastasis in lymph node

Radial ScarRadial Scar

• Mimics invasive carcinoma on Mimics invasive carcinoma on mammogram and on physical exam (if mammogram and on physical exam (if large enough to be palpable).large enough to be palpable).

• Bilateral in 45%.Bilateral in 45%.

• A frequent finding in women with A frequent finding in women with fibrocystic disease.fibrocystic disease.

• No risk for subsequent development of No risk for subsequent development of invasive carcinoma.invasive carcinoma.

Source Undetermined

A female presents complaining A female presents complaining of nipple pain during breast-of nipple pain during breast-feeding with focal erythema feeding with focal erythema

and warmth of breast on and warmth of breast on physical exam.physical exam.

Mastitis or Breast AbscessMastitis or Breast Abscess• Usual etiology: Staphylococcus aureus or Usual etiology: Staphylococcus aureus or

streptococcus infection.streptococcus infection.• Most commonly occurs during breast-feeding.Most commonly occurs during breast-feeding.• Focal tenderness with erythema possibly with a Focal tenderness with erythema possibly with a

fluctuant mass.fluctuant mass.• Ultrasound helpful with diagnosis.Ultrasound helpful with diagnosis.• Antibiotics with or without drainage is usual Antibiotics with or without drainage is usual

treatment.treatment.• If abscess needs drainage.If abscess needs drainage.

A 30 year old female presents A 30 year old female presents with a painful breast mass with a painful breast mass

several weeks after sustaining several weeks after sustaining significant trauma from a seat significant trauma from a seat

belt after an auto accident.belt after an auto accident.

Fat NecrosisFat Necrosis

• History of trauma in 50% of patients.History of trauma in 50% of patients.

• Often present after breast reconstruction.Often present after breast reconstruction.

• Irregular mass without discrete borders Irregular mass without discrete borders may or may not be tender.may or may not be tender.

• Often indistinguishable from carcinoma Often indistinguishable from carcinoma clinically or mammographically.clinically or mammographically.

• Diagnosis by excisional biopsy.Diagnosis by excisional biopsy.

Source Undetermined

A 38 year old female enters A 38 year old female enters your office with a history of a your office with a history of a large mass in her left breast. large mass in her left breast.

She states that it has expanded She states that it has expanded rapidly over the last month.rapidly over the last month.

Phyllodes Tumor Phyllodes Tumor (Crystosarcoma Phyllodes)(Crystosarcoma Phyllodes)

• <.5% of all breast tumors.<.5% of all breast tumors.• Majority are benign.Majority are benign.• A variant of fibroadenomaA variant of fibroadenoma• Most present as a large mass. Most present as a large mass. • Often present for many years before sudden Often present for many years before sudden

enlargement.enlargement.• Occasionally quite massive and stretch the skin, Occasionally quite massive and stretch the skin,

displace the nipple and distend overlying veins.displace the nipple and distend overlying veins.

Treatment of Phyllodes TumorTreatment of Phyllodes Tumor

• Excision with at least 1 cm margin.Excision with at least 1 cm margin.

• Simple Mastectomy or Lumpectomy.Simple Mastectomy or Lumpectomy.

• Axillary dissection usually not indicated Axillary dissection usually not indicated (axillary nodes palpable in 20% but (axillary nodes palpable in 20% but positive in <.5%).positive in <.5%).

• Radiation if chest wall involvement.Radiation if chest wall involvement.

• Chemotherapy for metastatic disease Chemotherapy for metastatic disease (sarcoma protocol).(sarcoma protocol).

8-20-04

Source Undetermined

A 60 year old male comes to A 60 year old male comes to your office complaining of your office complaining of bilateral enlargement of his bilateral enlargement of his

breasts over the last 6 months.breasts over the last 6 months.

GynecomastiaGynecomastia• Development of female like breast tissue in Development of female like breast tissue in

males.males.• Most common abnormality of male breast.Most common abnormality of male breast.• Often associated with other disease conditions, Often associated with other disease conditions,

hyperthyroidism, cirrhosis, chronic renal failure, hyperthyroidism, cirrhosis, chronic renal failure, pulmonary malignancy, testicular tumors.pulmonary malignancy, testicular tumors.

• Secondary to certain drug use: antibiotic Secondary to certain drug use: antibiotic steroids, digitalis, cimetidine, spironolactone, steroids, digitalis, cimetidine, spironolactone, marihuana, and tricyclic antidepressants.marihuana, and tricyclic antidepressants.

A 35 year old lady undergoes a right breast A 35 year old lady undergoes a right breast excisional biopsy for a suspected excisional biopsy for a suspected fibroadenoma. Pathology returns fibroadenoma. Pathology returns

diagnosis of fibroadenoma + LCIS or diagnosis of fibroadenoma + LCIS or atypical ductal hyperplasia.atypical ductal hyperplasia.

High Risk Lesions of the BreastHigh Risk Lesions of the Breast

• Atypical ductal hyperplasia.Atypical ductal hyperplasia.

• Lobular carcinoma in-situ.Lobular carcinoma in-situ.

• If found must do wire localization If found must do wire localization excisional biopsy 15-20% have DCIS.excisional biopsy 15-20% have DCIS.

• Do not need margins for LCIS or ADH.Do not need margins for LCIS or ADH.

Lobular Carcinoma In-Situ (LCIS)Lobular Carcinoma In-Situ (LCIS)

• A predictor of increased risk of subsequent A predictor of increased risk of subsequent invasive carcinoma.invasive carcinoma.

• If invasive carcinoma develops most are ductal.If invasive carcinoma develops most are ductal.• Risk of 20 to 30% bilateral.Risk of 20 to 30% bilateral.• Almost always found incidentally.Almost always found incidentally.• No mammographic finding.No mammographic finding.• 20-25% of women will develop invasive cancer.20-25% of women will develop invasive cancer.

Treatment of LCISTreatment of LCIS

• Careful follow-up (physical exam every 6 Careful follow-up (physical exam every 6 months and mammogram yearly).months and mammogram yearly).

• Prophylactic bilateral simple mastectomies Prophylactic bilateral simple mastectomies with or without reconstruction.with or without reconstruction.

• Chemoprevention with Tamoxifen or Chemoprevention with Tamoxifen or other agent.other agent.

Source Undetermined

A 45 year old female comes to A 45 year old female comes to your office with a mammogram your office with a mammogram containing microcalifications.containing microcalifications.

Differential Diagnosis of Differential Diagnosis of MicrocalcificationsMicrocalcifications

• 15% will be malignant.15% will be malignant.

• Invasive carcinoma of breast.Invasive carcinoma of breast.

• Ductal carcinoma in-situDuctal carcinoma in-situ

• Benign causesBenign causes• FibroadenomaFibroadenoma• Sclerosing adenosisSclerosing adenosis• Fibrocystic diseaseFibrocystic disease

Ductal Carcinoma In-SituDuctal Carcinoma In-Situ• Usually heralded by microcalifications on Usually heralded by microcalifications on

mammography.mammography.• Sometimes associated with a mass.Sometimes associated with a mass.• Must excise with 3 mm margin.Must excise with 3 mm margin.• Treat with radiation post-op.Treat with radiation post-op.• Sentinel lymph node biopsy usually not Sentinel lymph node biopsy usually not

necessary.necessary.• If recurs 50% are invasive.If recurs 50% are invasive.• Most recur within 1 cm of previous excision.Most recur within 1 cm of previous excision.• If ER+, PR+ treat with SERM.If ER+, PR+ treat with SERM.

Source Undetermined

Source Undetermined

A 45 year old female presents to A 45 year old female presents to your office with a mass in her your office with a mass in her right breast which she identified right breast which she identified 1 month ago while showering.1 month ago while showering.

Important Historical QuestionsImportant Historical Questions• When was last mammogram.When was last mammogram.• Family history of breast cancer.Family history of breast cancer.• Age at menarche.Age at menarche.• Age at menopause (if appropriate).Age at menopause (if appropriate).• Age at first pregnancy.Age at first pregnancy.• History of ionizing radiation exposure.History of ionizing radiation exposure.• Postmenopausal hormone replacement therapy.Postmenopausal hormone replacement therapy.• Use of oral contraceptives.Use of oral contraceptives.• Did the patient breast feed children.Did the patient breast feed children.

Increased RiskIncreased Risk

• Prior personal history of breast cancer.Prior personal history of breast cancer.• History of atypical ductal hyperplasia or LCIS.History of atypical ductal hyperplasia or LCIS.• Early menarche < 13 years.Early menarche < 13 years.• Late menopause Late menopause >> 55 years. 55 years.• Nulliparity.Nulliparity.• Exposure to radiation.Exposure to radiation.• First degree relative with breast cancer, prostate cancer First degree relative with breast cancer, prostate cancer

or ovarian cancer.or ovarian cancer.• Postmenopausal hormone replacement.Postmenopausal hormone replacement.• Genetic predisposition (BRCA 1 or 2, P53, mutation).Genetic predisposition (BRCA 1 or 2, P53, mutation).

Diagnostic OptionsDiagnostic Options

• Mammography.Mammography.• Ultrasound.Ultrasound.• Core biopsy (percutaneous or image guided).Core biopsy (percutaneous or image guided).• Fine needle aspiration (FNA).Fine needle aspiration (FNA).• Wire localization excisional biopsy.Wire localization excisional biopsy.• Excisional biopsy.Excisional biopsy.• Sentinel lymph node biopsy.Sentinel lymph node biopsy.• FNA of lymph nodes.FNA of lymph nodes.

MammographyMammography

• Sensitivity 80-90%.Sensitivity 80-90%.• Identifies about 5 cancers/1000 women.Identifies about 5 cancers/1000 women.• If detected by mammography 80% have If detected by mammography 80% have

negative nodes vs. 45% if detected negative nodes vs. 45% if detected clinically.clinically.

• Much less effective in < 35 age group and Much less effective in < 35 age group and in patients who have taken endogenous in patients who have taken endogenous hormones.hormones.

UltrasoundUltrasound

• No ionizing radiationNo ionizing radiation

• Cheap.Cheap.

• Good for identifying cystic disease.Good for identifying cystic disease.

• Can aid in biopsying a mass or Can aid in biopsying a mass or calcifications.calcifications.

• May be helpful in patients with dense May be helpful in patients with dense breast tissue.breast tissue.

Fine Needle Aspiration (FNA)Fine Needle Aspiration (FNA)

• Low morbidity.Low morbidity.

• Cheap.Cheap.

• False positive 1-2%.False positive 1-2%.

• False negative up to 10%.False negative up to 10%.

• Requires a skilled pathologist.Requires a skilled pathologist.

• More difficult to determine receptor More difficult to determine receptor status.status.

Stereotactic Core BiopsyStereotactic Core Biopsy

• Fewer complications compared to wire Fewer complications compared to wire localization.localization.

• Less chance of a sampling error than core Less chance of a sampling error than core biopsy alone.biopsy alone.

• Does not require OR.Does not require OR.

• Receptor status easily determined.Receptor status easily determined.

• Used for non-palpable lesions.Used for non-palpable lesions.

Wire Localization BiopsyWire Localization Biopsy

• Requires the OR.Requires the OR.• May cause deformity of the breast.May cause deformity of the breast.• Requires a surgeon.Requires a surgeon.• Must coordinate surgeon and radiologist Must coordinate surgeon and radiologist

times.times.• Non-palpable lesions.Non-palpable lesions.• May be necessary depending on location May be necessary depending on location

of the lesion.of the lesion.

Breast Cancer EpidemiologyBreast Cancer Epidemiology

• One in 8 women will contract.One in 8 women will contract.• Approximately 215,000 new cases in Approximately 215,000 new cases in

United States this year.United States this year.• 15% of all cancer deaths in women in U.S.15% of all cancer deaths in women in U.S.• Incidence increases with age.Incidence increases with age.• More common in Caucasians except in the More common in Caucasians except in the

under 40 age group.under 40 age group.• <1% occur in men.<1% occur in men.

Invasive Ductal CarcinomaInvasive Ductal Carcinoma

• Most common type of invasive carcinoma Most common type of invasive carcinoma of the breast 75-80%.of the breast 75-80%.

• Most common sites of metastasis are Most common sites of metastasis are axilla, lungs, liver, bone, and brain.axilla, lungs, liver, bone, and brain.

• Usually diagnosed after finding a mass on Usually diagnosed after finding a mass on mammography or by palpation.mammography or by palpation.

Treatment OptionsTreatment Options• Lumpectomy and sentinel lymph node (SLNB) Lumpectomy and sentinel lymph node (SLNB)

biopsy.biopsy.• Mastectomy and sentinel lymph node (SLNB) Mastectomy and sentinel lymph node (SLNB)

biopsy.biopsy.• Lumpectomy or mastectomy and axillary lymph Lumpectomy or mastectomy and axillary lymph

node dissection (ALND).node dissection (ALND).• Neoadjuvant chemotherapy.Neoadjuvant chemotherapy.• Hormonal therapy.Hormonal therapy.• Adjuvant chemotherapy.Adjuvant chemotherapy.• Radiation therapy.Radiation therapy.

Receptor Status of TumorReceptor Status of Tumor• Estrogen receptor + better prognosis. Can use SERMS Estrogen receptor + better prognosis. Can use SERMS

(Selective estrogen receptor modulators).(Selective estrogen receptor modulators).• Estrogen receptor (-). Worse prognosis SERMS not Estrogen receptor (-). Worse prognosis SERMS not

effective.effective.• HER-2-NEU receptor overexpressed worse prognosis.HER-2-NEU receptor overexpressed worse prognosis.• Current controversy over use of SERMS in ER –PR+ Current controversy over use of SERMS in ER –PR+

patients.patients.• ER+ tumors have poorer response to chemotherapy.ER+ tumors have poorer response to chemotherapy.

Source Undetermined

Source Undetermined

Invasive Lobular CarcinomaInvasive Lobular Carcinoma

• 5-15% of all invasive carcinomas of the female 5-15% of all invasive carcinomas of the female breast.breast.

• Usually presents as ill-defined, painless mass or Usually presents as ill-defined, painless mass or a vague thickening or nodularity.a vague thickening or nodularity.

• Tends to be more extensive than mammography Tends to be more extensive than mammography suggest.suggest.

• 15-30% multicentric.15-30% multicentric.• Contralateral carcinoma develops in 10% to Contralateral carcinoma develops in 10% to

15%.15%.• Treatment is same as invasive ductal carcinoma.Treatment is same as invasive ductal carcinoma.

Source Undetermined

Other Types of Breast CancerOther Types of Breast Cancer

• PapillaryPapillary

• TubularTubular

• MedullaryMedullary

• InflammatoryInflammatory

• PagetPaget’’s Diseases Disease

• Male Breast CancerMale Breast Cancer

Inflammatory Breast CancerInflammatory Breast Cancer

• One to 2% of all invasive breast cancers.One to 2% of all invasive breast cancers.• Most lethal breast cancer.Most lethal breast cancer.• Vascular and lymphatic invasion commonly seen Vascular and lymphatic invasion commonly seen

at pathologic evaluation.at pathologic evaluation.• Frequently presents with erythema, Frequently presents with erythema, ““peau peau

dd’’orangeorange””, and nipple retraction., and nipple retraction.• Treatment is neoadjuvant chemotherapy Treatment is neoadjuvant chemotherapy

followed by surgery and radiation.followed by surgery and radiation.• Surgical treatment is a Modified Radical Surgical treatment is a Modified Radical

Mastectomy.Mastectomy.

PagetPaget’’s Disease of the Breasts Disease of the Breast• About 2% of all invasive breast cancers.About 2% of all invasive breast cancers.• Usually associated with underlying ductal carcinoma Usually associated with underlying ductal carcinoma

extending within the epithelium of the main excretory extending within the epithelium of the main excretory ducts to the skin of the nipple and areola.ducts to the skin of the nipple and areola.

• Presentation: Tender, itchy nipple with or without Presentation: Tender, itchy nipple with or without bloody discharge with or without subareolar palpable bloody discharge with or without subareolar palpable mass.mass.

• Treatment is either central segmentectomy or Treatment is either central segmentectomy or mastectomy with SLN or ALND.mastectomy with SLN or ALND.

• Chemotherapy and/or radiation as indicated.Chemotherapy and/or radiation as indicated.

Source Undetermined

Breast Cancer In MalesBreast Cancer In Males• Less than 1% of all breast cancers.Less than 1% of all breast cancers.• Predisposing factors: KlinefeltorPredisposing factors: Klinefeltor’’s Syndrome, s Syndrome,

estrogen therapy, elevated endogenous estrogen, estrogen therapy, elevated endogenous estrogen, previous irradiation and trauma.previous irradiation and trauma.

• Infiltrating ductal carcinoma most common.Infiltrating ductal carcinoma most common.• Diagnosis tends to be late often with mass, Diagnosis tends to be late often with mass,

nipple retraction and skin changes.nipple retraction and skin changes.• Stage by stage survival is same as women.Stage by stage survival is same as women.• Treatment involves mastectomy and SLNB/or Treatment involves mastectomy and SLNB/or

ALND.ALND.

Breast Cancer in Pregnant and Breast Cancer in Pregnant and Lactating WomenLactating Women

• Three breast cancers per 10,000 pregnancies.Three breast cancers per 10,000 pregnancies.• Biopsy should be done if there is a suspicious Biopsy should be done if there is a suspicious

mass.mass.• Mammography can be done if there is proper Mammography can be done if there is proper

shielding.shielding.• Radiation is not advised for pregnant women Radiation is not advised for pregnant women

therefore MRM is advised.therefore MRM is advised.• Delay chemotherapy to the second trimester.Delay chemotherapy to the second trimester.• Suppress lactation after delivery.Suppress lactation after delivery.

Common Chemotherapeutic DrugsCommon Chemotherapeutic Drugs

• Anthracyclines (Adriamycin)Anthracyclines (Adriamycin)

• Cyclophosphamide (Cytoxan)Cyclophosphamide (Cytoxan)

• 5-fluorouracil5-fluorouracil

• Taxanes (Paclitaxel, Taxotere)Taxanes (Paclitaxel, Taxotere)

• Trastusamab (Herceptin)Trastusamab (Herceptin)

Other AgentsOther Agents

• Monoclonal antibodiesMonoclonal antibodies• Transtuzumab (Herceptin)Transtuzumab (Herceptin)• Bevacizumab (Avastin)Bevacizumab (Avastin)

• Impedes neovascularizationImpedes neovascularization

• Interferes with VEGFInterferes with VEGF

• Bisphosphonates – inhibits Osteoclastic Bisphosphonates – inhibits Osteoclastic activityactivity

• ZometaZometa

Hormone ManipulationHormone Manipulation

• Tamoxifen (receptor blocker)Tamoxifen (receptor blocker)

• Aromatase inhibitorAromatase inhibitor• Arimidex (anastrozole)Arimidex (anastrozole)• Femara (letrozole)Femara (letrozole)• Exemestane (aromasin)Exemestane (aromasin)

• Faslodex (fulvestrant)Faslodex (fulvestrant)

RadiationRadiation

• Give when breast sparing procedureGive when breast sparing procedure

• Give when tumor involves the chest wall Give when tumor involves the chest wall or skin.or skin.

• Give when four or more nodes positive.Give when four or more nodes positive.

• Decrease local recurrence by 40-50%.Decrease local recurrence by 40-50%.

Oncotype DXOncotype DX

• Gene – based assay of tumor tissueGene – based assay of tumor tissue• Helps determine the risk of recurrenceHelps determine the risk of recurrence• Helps guide chemotherapy decisionsHelps guide chemotherapy decisions• Applies to ERApplies to ER+ HER2NEUHER2NEU- patients patients• Patients must be node negative or have Patients must be node negative or have

micrometastasis .2-2mmmicrometastasis .2-2mm• Tumors 6 mm – 1 cm with moderately to poorly Tumors 6 mm – 1 cm with moderately to poorly

differentiated features or unfavorable featuresdifferentiated features or unfavorable features• Tumors > 1 cm with favorable featuresTumors > 1 cm with favorable features• TAILOR X trialTAILOR X trial

Referral for Genetics EvaluationReferral for Genetics EvaluationAn affected individual with 1 or more ofAn affected individual with 1 or more of::

•Early age onset breast cancerEarly age onset breast cancer

•Triple negative diseaseTriple negative disease

•Two primary breast cancersTwo primary breast cancers

•Breast cancer at any age, plusBreast cancer at any age, plus• ≥ ≥ 1 Close relative with breast cancer under age 501 Close relative with breast cancer under age 50• ≥ ≥ 1 Close relative with ovarian, fallopian tube or 1 Close relative with ovarian, fallopian tube or

primary peritoneal cancer at any ageprimary peritoneal cancer at any age• ≥ ≥ 2 Close relatives with breast cancer or pancreatic 2 Close relatives with breast cancer or pancreatic

cancer at any agecancer at any age

Referral for Genetics EvaluationReferral for Genetics Evaluation

An affected individual with one or more of:An affected individual with one or more of:

•Combination of breast cancer with one or more of:Combination of breast cancer with one or more of:• Thyroid cancer, sarcoma, adrenocortical carcinoma, Thyroid cancer, sarcoma, adrenocortical carcinoma,

endometrial cancer, pancreatic cancer, brain cancer, endometrial cancer, pancreatic cancer, brain cancer, diffuse gastric cancer, mucocutaneous lesions or diffuse gastric cancer, mucocutaneous lesions or leukemia/lymphoma on the same side of the familyleukemia/lymphoma on the same side of the family

•Ovarian, fallopian tube or primary peritoneal CAOvarian, fallopian tube or primary peritoneal CA

•Male breast cancerMale breast cancer

Referral for Genetics EvaluationReferral for Genetics EvaluationAn unaffected individual with a FHx of 1 or more of:An unaffected individual with a FHx of 1 or more of:•≥ ≥ 2 Breast cancer primaries from same side2 Breast cancer primaries from same side•≥ ≥ 1 Ovarian cancer primaries from same side1 Ovarian cancer primaries from same side•Combination of breast cancer with 1 or more of:Combination of breast cancer with 1 or more of:

• Thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial Thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain cancer, diffuse gastric cancer, cancer, pancreatic cancer, brain cancer, diffuse gastric cancer, mucocutaneous lesions or leukemia/lymphoma from same side mucocutaneous lesions or leukemia/lymphoma from same side of familyof family

•Known mutation in breast cancer geneKnown mutation in breast cancer gene•Male breast cancerMale breast cancer•From a population at riskFrom a population at risk

GeneticsGenetics

• Malone et al conducted a population based case Malone et al conducted a population based case control study on data from 1983-1992control study on data from 1983-1992• The likelihood that a women with breast cancer under The likelihood that a women with breast cancer under

age 35 has a detectable BRCA1/2 mutation is 9.4%age 35 has a detectable BRCA1/2 mutation is 9.4%

Malone et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of Malone et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. young breast carcinoma cases. Cancer.Cancer. 2000; 88:1393-1402. 2000; 88:1393-1402.

GeneticsGenetics

• Li-Fraumeni SyndromeLi-Fraumeni Syndrome• Autosomal dominantAutosomal dominant• Highly penetrantHighly penetrant• Young age at onset of malignanciesYoung age at onset of malignancies• Identifiable germline mutation in TP53Identifiable germline mutation in TP53

GeneticsGenetics

• Li-Fraumeni syndrome diagnostic criteriaLi-Fraumeni syndrome diagnostic criteria• A proband diagnosed with sarcoma when A proband diagnosed with sarcoma when

younger than 45 years of ageyounger than 45 years of age• A first-degree relative with any cancer A first-degree relative with any cancer

diagnosed when younger than 45 years of agediagnosed when younger than 45 years of age• Another first-degree or second-degree relative Another first-degree or second-degree relative

of the same genetic lineage with any cancer of the same genetic lineage with any cancer diagnosed when younger than 45 years or diagnosed when younger than 45 years or sarcoma at any agesarcoma at any age

GeneticsGenetics

• CowdenCowden’’s syndromes syndrome• Autosomal dominantAutosomal dominant• Variable expression, high penetranceVariable expression, high penetrance• Prevalence of 1 in 200,000Prevalence of 1 in 200,000• Mutation in PTENMutation in PTEN• Breast cancer in 20-35%Breast cancer in 20-35%