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Breast Cancer 101

Breast Cancer 101. Sandra M. Swain, MD Chief, Cancer Therapeutics Branch Center for Cancer Research National Cancer Institute Swains@mail.nih.gov November 17, 2003. Dr. Bernard Fisher.

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Breast Cancer 101

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  1. Breast Cancer 101 Sandra M. Swain, MD Chief, Cancer Therapeutics Branch Center for Cancer Research National Cancer Institute Swains@mail.nih.gov November 17, 2003

  2. Dr. Bernard Fisher “ It is evident that we have embarked upon an era of medicine in which success results in the genesis of difficult problems.”

  3. US Breast Cancer Statistics • 2003 estimates • 211,300 new cases (32% of cancers) • 39, 800 deaths (15% of deaths) • Most common cancer in women • Second leading cause of cancer death (lung first) • 1 in 8 women will develop breast cancer in their lifetime (to age 85 years) American Cancer Society

  4. Breast Cancer Incidence1983-1995

  5. 87 98 White All Stages 78 Localized 23 Regional Distant 71 African 89 American 62 14 0 20 40 60 80 100 120 % Surviving 5 Years BREAST CANCER5-year relative survival rates by race Landis SH, et al. CA Cancer J Clin. 1999;49:8-31.

  6. Breast Cancer Theories • Halsted • breast cancer is a local-regional disease • the positive lymph node is source of distant metastases • Systemic • breast cancer is a systemic disease • positive lymph node is an indicator of host-tumor relationship that permits metastases • Spectrum • breast cancer is a systemic disease in many but not all • positive lymph node is correlated with the subsequent appearance of distant metastases

  7. BREAST CANCERRisk 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 Henderson IC. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;198-219. Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616. Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;231-257.

  8. NSABP P1 Eligible Participants Stratification • Age • Relative Risk • Race PLACEBO X 5 YRS. TAMOXIFEN X 5 YRS.

  9. Invasive Breast Cancers NSABP P1 Placebo Tamoxifen 175 89 P < 0.00001 49% reduction

  10. Noninvasive Breast Cancers NSABP P1 Placebo Tamoxifen 69 35 P = 0.002 50% reduction

  11. BREAST CANCERScreening mammography 2003 • Reduces mortality by 26% in women aged 50-74, 17% in women 40-49 • ACS recommends • Mammography at age 40 and annually thereafter • 20 or older, BSE is an option • 20-39 breast exam by physician every three years, 40 or older every year • Women at high risk discuss with physician

  12. BREAST CANCERSigns and symptoms at presentation • Mass or painin the axilla • Palpable mass • Thickening • Pain • Nipple discharge • Nipple retraction • Edema or erythemaof the skin

  13. BREAST CANCERMammography

  14. BREAST CANCERUltrasonography

  15. BREAST CANCERDiagnosis path Normal Evaluation for biopsy Cyst Palpable mass Nonpalpable mass Cyst aspiration • Biopsy • Excisional biopsy • Core-cutting needle biopsy • Fine-needle aspiration Needle localization If persistent, short-term follow-up with surgeon Continued appropriate screening Insufficient evaluation, rebiopsy Ductal carcinoma in situ Invasive cancer Lobular carcinoma in situ Benign Treatment Path

  16. BREAST CANCERBiopsy techniques for palpable and mammographically detected masses • Excisional biopsy (usually outpatient) • Tumor size and histologic diagnosis • Core-cutting needle biopsy – Mammatome (in-office) • Histologic diagnosis • Fine-needle aspiration (in-office) • Cytologic diagnosis Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616.

  17. BREAST CANCERPathology • Non-invasive carcinoma in situ • Ductal carcinoma in situ (DCIS) • Lobular carcinoma in situ (LCIS) • Invasive carcinoma • Infiltrating ductal or lobular carcinoma • Medullary, mucinous, and tubular carcinomas • Uncommon • Inflammatory carcinoma • Paget’s disease Dollinger M, et al. Everyone’s Guide toCancer Therapy. 1997;356-384.

  18. 80% 10% 5% Infiltrating Lobular Medullary BREAST CANCERIncidence of major histologic types Percent of all invasive carcinomas Hendersn IC. American Cancer Society Textbook & Clinical Oncology. 1995;198-219.

  19. BREAST CANCERInvasive ductal carcinoma

  20. BREAST CANCERPathology: Non-invasive DCIS & LCIS DCIS LCIS  Abnormal mammogram  Microscopic characterization on biopsy  Clustered microcalcifications  Solid proliferation of small or non-palpable masses cells with uniform round to oval nuclei  30% risk of invasive cancer  37% chance of subsequent at 10 years at or near invasive cancer original biopsy site DCIS – ductal carcinoma in situ. LCIS – lobular carcinoma in situ. Harris J, et al. Cancer: Principles & Practice of Chemotherapy. 5th ed. 1997;1557-1616. Love S, Barsky SH. Cancer Treatment. 4th ed. 1995;337-340.

  21. Ductal carcinoma in situ • Screening mammography has increased rate of detection of DCIS • Therapy • Simple mastectomy • Lumpectomy plus radiation (axillary lymph node dissection not required)

  22. DCIS: lumpectomy and radiation NSABP B17 Lumpectomy with radiation therapy decreased the incidence of both invasive and non-invasive cancer when compared with lumpectomy alone. (NSABP-B17) Fisher, B et al, J Clin Onc 16:441-452,1998

  23. DCIS: NSABP B-24 Fisher, B, Lancet 353:1993-2000, 1999

  24. BREAST CANCERSpread to lymph nodes Supraclavicular Subclavicular Distal (upper) axillary Central (middle) axillary Proximal (lower) axillary Mediastinal Internal mammary Interpectoral (Rotter’s)

  25. T1:  2 cm T1mic microinvasion  0.1 cm T1a 0.2 - 0.5 cm T1b 0.6 – 1 cm T1c 1.1 – 2 cm T2: 2.1- 5 cm T3: > 5 cm T4a: Extension to chest wall, not including pectoralis T4b: Edema, ulceration, satellite skin nodules T4c: both T4a and T4b T4d: inflammatory ca 2003 AJCC: Primary Tumor (T)

  26. BREAST CANCERStage I T1 N0 M0 T1a: T  0.5 cm T1b: 0.5 cm < T  1 cm T1c: 1 cm < T  2 cm T1 T  2 cm N0 = no regional lymph node metastasisM0 = no distant metastasis

  27. BREAST CANCERStage IIA } T0 T1 T2 N0 M0 N1 M0 No evidence of tumor T0 T2 2 cm < T < 5 cm N1 = metastasis to movable ipsilateral axillary lymph node(s)M0 = no distant metastasis

  28. BREAST CANCERStage IIB T2 N1 M0 T3 N0 M0 T3 T > 5 cm N1 = metastasis to movable ipsilateral axillary lymph node(s) (p) N1a, N1bM0 = no distant metastasis

  29. BREAST CANCERStage IIIA T0 T1 T2 T3 N2 M0 T3 N1 M0 Metastasis to ipsilateral axillary lymph node(s) N1 = movable N2 = fixed to one another or to other structures M0 = no distant metastasis

  30. N0: No regional lymph nodes N1: movable ipsilateral axillary LN N2: N2a: Fixed or matted ipsilateral LN N2b: Clinically apparent ipsilateral internal mammary LN (I.e. seen on imaging, not scintigraphy) without axillary LN N3: N3a: Ipsilateral infraclavicular LN N3b: Ipsilateral int mammary AND axillary N3c: Ipsilateral supraclavicular LN 2003 AJCC: Regional LN (N)

  31. pN0 (i+): No histological (H&E) LN, no IHC >0.2 cm pN1: 1-3 + LN, no clinically apparent int mammary LN pN1mi: 0.3 – 2.0 mm pN1b: int mammary by sentinal node pN1c: 1-3 axillary plus int mamm LN by sentinal node pN2 pN2a: 4-9 axil LN or pN2b: clinical int mamm LN without axil LN pN3 pN3a: 10+ axil LN or any infraclav LN pN3b: clinical int mamm LN + axil LN or 4+ axil and int mamm LN (not clin apparent) pN3c: ipsilat supraclav LN 2003 AJCC: Pathologic LN

  32. AJCC 2003: Stage Grouping

  33. 2003 AJCC: Stage Grouping

  34. BREAST CANCERCommonly assessed prognostic factors • Number of positive axillary nodes • Tumor size • Lymphatic and vascular invasion • Histologic tumor type • Histologic grade • Nuclear grade • Estrogen/progesteronereceptors • HER2/neu overexpression Slamon DJ. Chemotherapy Foundation. 1999;46. Harris J, et al. Cancer: Principles & Practice of Oncology. 1997;1557-1616.

  35. EARLY BREAST CANCER TRIALISTS’COLLABORATIVE GROUP (EBCTCG) Meets in Oxford every 5 years to review centrally collected data on all randomized trials in early breast cancer (Adjuvant trials) Year 2000: data from 300 trials involving 200,000 women, of whom 70,000 had died

  36. Early Breast Cancer Trialists’ Collaborative Group Impact of Prolonged Polychemotherapy On Absolute Risk Reduction at 10 years (in % ) Death 4.5 (SE 1.5) 11.3 (SE 2.4) 3.2 (SE 1.4) 3.0 (SE 1.1) Subgroup Age < 50, Node- Age < 50, Node+ Age 50-69, Node- Age 50-69, Node+ Recurrence 11.1 (SE 2.2) 12.1 (SE 2.5) 4.3 (SE 1.4) 5.5 (SE 1.4) Oxford 9/2000

  37. Early Breast Cancer Trialists’ Collaborative Group Impact of Prolonged Polychemotherapy On Reducing (in % ± SD) Annual Odds of... Subgroup (N) Age < 50, Age  50, Recurrence 36 ( SE 3) 19 ( SE 2) Death 27 ( SE 4) 11 ( SE 2) Oxford 9/2000

  38. Proportional Risk Reduction • Recurrence rate is 20%, absolute decrease in recurrence is 5%, the proportional risk reduction is • .05/.20 = .25 or 25%

  39. Worldwide Overview: All Age Groups % Reduction in Annual Odds (SD) Recurrence Death Tamoxifen vs no tamoxifen 25 (2) 16 (2) Node-negative 26 (4) 17 (5)Node-positive 28 (2) 18 (2) ER-poor (<10 fmol/mg) 13 (4) 11 (5)ER-positive (10 fmol/mg) 32 (3) 21 (3)ER unknown 22 (3) 15 (3) Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1992;339:1-15.

  40. Node- negative breast cancer The majority of women with lymph node negative breast cancer receive adjuvant systemic therapy, often a combination of chemotherapy and hormonal therapy

  41. Node Negative Breast CancerNSABP B-20 FisherB, et al, JNCI 22: 1673-82,1997

  42. St Gallen’s 2003Node NegativeMinimal risk • Endocrine • Responsive ER and/or PR expressed AND ALL: pT < 2 cm Grade 1 Age > 35 yrs JCO, 19: 3817-27,2001

  43. St Gallen’s 2003Node NegativeAverage Risk • Endocrine • Responsive • Endocrine • Nonresponsive ER and/or PR expressed and at least one: pT > 2 cm or Grade 2 or 3 or Age < 35 yrs ER and/or PR neg

  44. St Gallen’s 2003Systemic Treatment RecommendationsNode neg, Minimal risk • Endocrine Responsive Pre T or Nil or Post

  45. St Gallen’s 2003 Systemic Treatment RecommendationsNode neg, Average risk • Endocrine Responsive • Endocrine Nonresponsive • Ov+T (+Chemo) • Chemo  T (+Ov) • T • Ov • Pre • Post • Pre • or • post • T • Chemo+T Chemo

  46. Lymph Node Positive Breast Cancer • ER negative • chemotherapy (pre-menopausal or post-menopausal) • ER positive • premenopausal: chemotherapy + tamoxifen** • postmenopausal: tamoxifen + chemotherapy • elderly: tamoxifen ** ovarian ablation/GnRH analog may be considered

  47. Mechanisms of Action of Tamoxifen Citrate • Mainly cytostatic • Binds to estrogen receptors • Effects on TGFs, IGF-1, and SHBG • Mixed estrogen antagonist/agonist • Antagonist: breast tissue • Agonist: endometrium, bone, lipids • Tamoxifen-resistance: mechanisms unknown

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