BREAST CANCER B.KLEIN ONCOLOGY MEIR HOSPITAL. CASE REPORT 40 Yrs old woman felt a lump in her left breast Px : 3x2cm mass in LUQ moveable. No LN palpated.

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•