BREAST CANCER
B.KLEIN
ONCOLOGY
MEIR HOSPITAL
Mortality Rates in Patients With Breast Cancer Aged 50 to 69 Years
0
Year
105
90
75
60
45
30
15
1950 1960 1970 1980 1990 2000
An
nu
al d
eat
h r
ate
per
100
,00
0 w
om
en
UK
USA
Reprinted with permission from Elsevier Science (Lancet. 2000;355:1822).
CASE REPORT
40 Yrs old woman felt a lump in her left breast
Px : 3x2cm mass in LUQ moveable. No LN
palpated
She underwent L lumpectomy +LN dissection
Pathology:G3 IDC+20% DCIS, T=2.5 cm N=2+/15, vascular invasion.
ER= 0%, PR= O% HER-2 +++(HIC)
Parkin et al. Eur J Cancer. 2001;37:S4.Fisher et al. J Natl Cancer Inst Monographs. 2001;30:62.*American Joint Committee on Cancer. Handbook for Staging of Cancer; 1993.
Breast Cancer
• Worldwide estimates for 2001– 1,050,000 new cases
– 370,000 breast cancer–related deaths
• Second leading cause of cancer death in women• Outcome is directly related to stage at diagnosis,
eg, survival after 5 years* – Stage I disease 95%– Stage II disease 70%-85%– Stage III disease 50%-52%– Stage IV disease 17%
BREAST CANCERBREAST CANCERRisk factorsRisk factors
Age
Family history of breast cancer
Prior personal history of breast cancer
Increased estrogen exposure– Early menarche– Late menopause– Hormone replacement therapy/oral contraceptives
Nulliparity
1st pregnancy after age 30
Diet and lifestyle (obesity, excessive alcohol consumption)
Radiation exposure before age 40
Prior benign or premalignant breast changes– In situ cancer– Atypical hyperplasia– Radial scar
Osteen RT. American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;251-268.Winer EP, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1651-1717.
Ductal carcinoma in situ
Infiltrating lobular carcinomaA normal duct (yellow arrow) is the center of cells arranged in concentric circles(white arrows).This “target pattern” is classic!
BREAST CANCERBREAST CANCERTumor definitionsTumor definitions TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no tumor
T1 Tumor 2 cm or less in greatest dimensionT1mic Microinvasion more than 0.1 cm or less in greatest dimensionT1a Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimensionT1b Tumor more than 0.5 cm but not more than 1 cm in greatest dimensionT1c Tumor more than 1 cm but not more than 2 cm in greatest dimension
T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension
T3 Tumor more than 5 cm in greatest dimension
T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described belowT4a Extension to chest wallT4b Edema (including peau d’orange) or ulceration of the skin of the breast
or satellite skin nodules confined to the same breastT4c Both (T4a and T4b)T4d Inflammatory carcinoma
Used with the permission of the American Joint Committee on Cancer (AJCC®), Chicago, Illinois. The original source for this material is the AJCC® Cancer Staging Manual, 5th edition (1997)
published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.
BREAST CANCERBREAST CANCERTNM stage groupingTNM stage grouping
Stage 0Stage 0 Tis N0 M0
Stage IStage I T1* N0 M0
Stage IIAStage IIA T0 N1 M0T1* N1** M0T2 N0 M0
Stage Stage IIBIIB T2 N1 M0T3 N0 M0
Stage IIIAStage IIIA T0, T1,* T2 N2 M0T3 N1, N2 M0
Stage IIIBStage IIIB T4 Any N M0Any T N3 M0
Stage IVStage IV Any T Any N M1
* Note: T1 includes T1 mic.** Note: The prognosis of patients with N1a is similar to that of patients with pN0.
Used with the permission of the American Joint Committee on Cancer (AJCC®), Chicago, Illinois. The original source for this material is the AJCC® Cancer Staging Manual, 5th edition (1997)
published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.
BREAST CANCERAnatomical site
RIGHT
Upper inner
Nipple
Central portion
Lower inner
Upper outer
Axillary tail
Lower outer
BREAST CANCERBREAST CANCERStage IStage I
T1a: T T1a: T 0.5 cm0.5 cm
T1b: 0.5 cm < T T1b: 0.5 cm < T 1 cm1 cm
T1c: 1 cm < T T1c: 1 cm < T 2 cm2 cm
T1 N0 M0T1 N0 M0
T T 2 cm2 cm
T1T1
N0 = no regional lymph node metastasisM0 = no distant metastasis
BREAST CANCERStage IIB
T3 N0 M0T3 N0 M0
N1 = metastasis to movable ipsilateral axillary lymph node(s) (p) N1a, N1bM0 = no distant metastasis
T > 5 cmT > 5 cm
T2 N1 M0T2 N1 M0
T3T3
B r e a s t C a n c e r S u r v i v a l R a t e A c c o r d i n g t o S t a g e
0
2 0
4 0
6 0
8 0
1 0 0
0 1 2 3 4 5 6
Y e a r s a f te r d ia g n o s is
% A
live
S t a g e I
S t a g e I IA
S t a g e I IB
S t a g e I I I A
S t a g e I I I B
S t a g e I V
R ie s e t a l. S E E R C a n c e r S t a t is t ic s R e v ie w , 1 9 7 3 - 1 9 9 6 . N C I , 1 9 9 9 .
P a t i e n t s D i a g n o s e d B e t w e e n 1 9 8 3 a n d 1 9 8 7
BREAST CANCERCommonly assessed prognostic
factors
Slamon DJ. Chemotherapy Foundation. 1999;46.Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1651-1717.
Nuclear grade
Estrogen/progesteronereceptors
HER2/neu overexpression
Number of positive axillary nodes
Tumor size
Lymphatic and vascular invasion
Histologic tumor type
Histologic grade
BREAST CANCER5-year survival as function of the
number of positive axillary lymph nodes
0%
20%
40%
60%
80%
5-Y
ear
Su
rviv
al5-
Yea
r S
urv
ival
0 1 2 3 4 5 6-10 11-15 16-20 >20
Number of Positive NodesNumber of Positive Nodes
Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616.
Anderson et al. Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology and end results database. J Clin Oncol. 2001;19:18. Reprinted with permission from the American Society of Clinical Oncology.
Breast Cancer Specific Survival by Joint Hormone Receptor Expression (SEER Data)
0.95
1.00
0.90
0.85
0.80
0.750 10 20 30 40 50 60 70 80
Survival (mo)
Cu
mu
lati
ve p
rop
ort
ion
su
rviv
ing
Joint ER/PR Phenotype
ER+PR+ (n=12,811)
ER+PR- (n=2,436)
ER-PR+ (n=663)
ER-PR- (n=3,631)
Node-negative patientswith T1-T3 tumors
Definitions
Early breast cancer
Locally advancedbreast cancer
Metastatic breast cancer
Breast cancer that is limitedto the breast and axilla
Tumors larger than 5cmwith adjacent structuresinvolvement or inflammatorycarcinoma
Tumors in supraclaviculararea and beyond
24
סוגי טיפול
(טיפול משלים, מסייע)טיפול אג'ובנטי•טיפול לאחר\ניתוח כאשר אין כל סימני מחלה.
לחסל את המיקרומטסטזותהמטרה: •
טיפול ניאואגובנטי•
ניתן לפני הניתוח בכדי להקטין את •הגידולולעשות אותו נתיח. לאתמיד הגידול בלתי
נתיח
Historical Perspective of Adjuvant Treatment of Breast Cancer
• Breast cancer treated as locoregional disease• Treatment = surgical approach
• Animal tumor models = breast cancer a systemic disease• Surgery + monotherapy ( Nissen-Meyer )
• Trials evaluating systemic therapy with less aggressive surgery (Veronesi)…establishing CMF (Bonadonna)
• Growth kinetics and trials support adjuvant therapy
• Trials with adjuvant CT – role of AC as U.S. standard regimen• PolyCT, tamoxifen, and polyCT + tam: efficacy debated
• Oxford overview analyses• Novel agents: taxanes, Herceptin• Biological predictive and prognostic factors
50’s
60’s
70’s
80’s
90’s
BCIRG JUNE 23, 2002
1995 Adjuvant Oxford OverviewRelative % Decrease in Mortality
TamChemoCombined
<50 y ER+25%25%45%
ER- 0%35%--
>50 y
ER+25%10%35%
ER- 0%20%--
BCIRG JUNE 23, 2002
Comparative Efficacy of Adjuvant Comparative Efficacy of Adjuvant Chemotherapy: EBCTCG Meta-AnalysesChemotherapy: EBCTCG Meta-Analyses
Therapy
Reduction inAnnual Odds, %
Recurrence Death
Polychemotherapy vs 23.5 15no chemotherapy (1995) (P < .00001) (P < .00001)
Anthracyclines vs 12 11CMF (1995) (P = .006) (P = .02)
Anthracyclines vs 10.815.7 CMF (2000) (P = .0005) (P < .00001)
BCIRG JUNE 23, 2002
Anthracycline-Based Treatment
Anthracycline-based regimens (epirubicin or doxorubicin) compared to those without
anthracyclines:–4 cycles of EC or AC equivalent to
6 cycles of CMF–more intense anthracycline-based regimens with
3 drugs (CEF/FEC/CAF) superior to CMF
BCIRG JUNE 23, 2002
Henderson Henderson et al.,et al., J Clin Oncol J Clin Oncol 2003; 2003; 6:6: 1–9 1–9
Adjuvant paclitaxelAdjuvant paclitaxel
NoneNone
3170 patients with (+) nodesMedian f/u 18 months
3170 patients with (+) nodesMedian f/u 18 months
(60 vs 75 vs 90)(60 vs 75 vs 90)
P 175 mg/m2 (3h)P 175 mg/m2 (3h)CC
AA
CALGB 9344 / Intergroup 0148CALGB 9344 / Intergroup 0148
No paclitaxel n = 1551 Events = 563 Median = NA Chi-square = 9.72Paclitaxel n = 1570 Events = 491 Median = NA p-value = 0.0018No paclitaxel n = 1551 Events = 563 Median = NA Chi-square = 9.72Paclitaxel n = 1570 Events = 491 Median = NA p-value = 0.0018
Disease-free survivalDisease-free survivalCALGB 9344CALGB 9344
By treatment armBy treatment arm
00
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
00 22 44 66
Years from study entryYears from study entry
Pro
po
rtio
n d
isea
se-f
ree
Pro
po
rtio
n d
isea
se-f
ree
No paclitaxel
Paclitaxel
Henderson Henderson et al.,et al., J Clin Oncol J Clin Oncol 2003; 2003; 21(b):21(b): 1–9 1–9
Receptor-positive tumorsReceptor-positive tumorsCALGB 9344CALGB 9344
Disease-free survival: Exploratory analysisDisease-free survival: Exploratory analysis
00
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
00 22 44 66
Pro
po
rtio
n d
isea
se-f
ree
Pro
po
rtio
n d
isea
se-f
ree
Years from study entryYears from study entry
No paclitaxel
Paclitaxel
Henderson Henderson et al.,et al., J Clin Oncol J Clin Oncol 2003; 2003; 21(b):21(b): 1–9 1–9
Years from study entryYears from study entry
Receptor-negative tumorsReceptor-negative tumorsCALGB 9344CALGB 9344
Disease-free survival: Exploratory analysisDisease-free survival: Exploratory analysis
00
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
00 22 44 66
Pro
po
rtio
n d
isea
se-f
ree
Pro
po
rtio
n d
isea
se-f
ree
No paclitaxel
Paclitaxel
Henderson Henderson et al.,et al., J Clin Oncol J Clin Oncol 2003; 2003; 21(b):21(b): 1–9 1–9
Tamoxifen in Early Breast Cancer
Adjuvant tamoxifen is indicated for– Receptor-positive patients regardless of age
– Pre- and postmenopausal women
– All nodal status
– Any tumor size
Exceptions may include – Premenopausal patients with tumor <1 cm, to avoid
side effects
– Postmenopausal patients with a history of thromboembolism
NIH Consensus Statement. 2000;17:1.
Risk Reduction With Tamoxifen in Early Breast Cancer According to Nodal Status
Early Breast Cancer Trialists’ Collaborative Group. Reprinted with permission from Elsevier Science (Lancet. 1998;351:1451).
100
Pe
rce
nt
90
80
60
40
20
05 10+0
Node -ve: 14.9% SD 1.4: 2P<0.00001Node +ve: 15.2% SD 2.5: 2P<0.00001
Node -
Node +
87.4
79.274.9
75.6 64.3
59.758.3
44.5
100
90
80
60
40
20
05 10+0
Node -ve: 5.6% SD 1.3: 2P<0.00001Node +ve: 10.9% SD 2.5: 2P<0.00001
Node -
Node +
91.8
78.989.3
74.2 73.3
50.5
80.1
61.4
70
50
30
10
70
50
30
10
Absolute Recurrence Reduction Absolute Mortality Reduction
Years Years
Pe
rce
nt
Tamoxifen (~5 y)
Control
Control
Tamoxifen (~5 y)
Recurrence as First Event Mortality From Any Cause
Tamoxifen (~5 y)
Control
Control
Tamoxifen (~5 y)
סיכום טיפול
. בלוטות חיוביות :כימוטרפיה.חולות פרה מנופאו•
אם רצפטורים חיוביים להוסיף טמוקסיפן או•
בלוטות שליליות:כימו או הורמונו.•
. בלוטות חיוביות רצפטורים חולות פוסטמנופאו•חיוביים אפשר להסתפק בהורמונים אפשר גם כימו
תלוי ברמת החיוביות.•
her-2חשיבות רבה ל•
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