1. Multi Disciplinary Cancer Management –Breast Cancer Dr Masalu N. MD Medical Oncologist

2. Breast Cancer Statistics II Medical Oncologist Nearly 50% of diagnoses and 60% of breast cancer deaths occur in underdeveloped countries Breast cancer 5 year survival ~89% in US (survival 75.2% in 1975), less than 40% in low income countries Screening reduces deaths from breast cancer in developed countries; impact of screening unknown in low income countries CA Cancer J Clin 2011, NCI SEER 2012, Lancet Oncology 2008

3. Stage 5 year survival 0100% I II93% III72% IV22% Most breast cancer cases in Tanzania present with stage IIIB or IV disease *NCI seercancer.gov Breast Cancer Survival According to Stage at Diagnosis Medical Oncologist Over 90% of US breast cancer cases present with localized or regional disease (nodes)*

4. Ductal Carcinoma In-Situ (DCIS) of the Breast Pathologist Clinical presentation: Incidental finding, mass, abnormal mammogram Natural history: Limited studies but up to 30% of women with partially resected lesions develop invasive cancer at 6-10 years Treatment: Mastectomy (99% cure) vs. lumpectomy +/- XRT Consider endocrine therapy for five years, especially if tumor ER positive

5. Lobular Carcinoma In-Situ Pathologist Clinical presentation: May lack mammographic signs, incidental, more common in premenopausal women, often multifocal or bilateral Natural history: Not a cancer but marker for increased risk (subsequent carcinoma in opposite breast 50% of the time and more often ductal histology) Risk of invasive cancer: ~1% annually Treatment: Cautious observation, rarely prophylactic bilateral mastectomy

6. Community Volunteers Spiritual counselor Nurse Hospice worker Physical therapist Pharmacist Physician Psychologist Social Worker Family Patient Interdisciplinary Team Medical Oncologist

7. Normal cells know : When to grow How to differentiate When to stop growing When to die (apoptosis) Neoplastic cells: Grow too much Do not differentiate Do not stop growing Do not die Malignant cancer cells can metastasize (spread

8. Pathologic features important in determining breast cancer treatment Estrogen and Progesterone receptors are located in the nucleus of the cell and are important factors in cell growth Estrogen and progesterone receptor status, HER- 2/neu, +/- Ki-67 status have documented clinical usefulness as tumor markers and choice of therapy Molecular profile (costly; limited access)

9. Breast Cancer Subtypes Pathologist SubtypePathologyPrevalenceCharacteristics Luminal AER and/or PR + HER2- Low Ki67 Grade 1-2 30-70%-Best prognosis -Fairly high survival rates -Fairly low recurrence rates Luminal B-ER and/or PR + -HER2+ or HER2- and high Ki67 -Higher tumor grade -Larger tumor size -More often node+ 10-20%-Prognosis good, but -Survival not as high as luminal Triple negative (basal-like) ER and PR- HER2- 15-20%-Aggressive -Poorer prognosis in first 5 years HER2 TypeER and PR- Typically HER2+ 5-15%-Younger age -Outcome improved with introduction of anti-HER2 agents

10. Treatment of cancer is multidisciplinary Medical Oncologist Surgery Tumor removal Radiation DNA Damage Chemotherapy DNA Disruption or damage Targeted Therapy Selective signal blocking Gene Therapy Replacement of gene function FUTURE: Personalized therapy “Identify which therapy will be more successful for each patient”

11. Primary Consultation: MS MS is 52 years old She works as a manager She has had a mass in her left breast for one year No pain No nipple secretion No skin changes or swollen glands Pregnancies 4 Deliveries3 Menarche at age 12; last period at 50 Never had a breast biopsy

12. Mother breast cancer at age 62 and a second primary at age 68 Sister breast cancer at age 57 Maternal aunt breast cancer at age 59 Maternal aunt ovarian cancer at age 68 Maternal uncle colon cancer at age 65 HBOC,BRCA1,BRCA2,LYNCH SYNDROME-HNPCC Family History

13. Vital signs: Temp 36.2 Pulse 89 Blood Pressure 137/67 A large 6x8 cm movable breast mass, without skin changes Axilla: Several enlarged lymph nodes Supraclavicular and cervical nodes: negative Liver feels normal

14. Should we order a mammogram?- Radiologist A. No need B. Only for the affected breast C. Only for the normal breast D. Mammogram for both breasts prior to biopsy E. Not now, only after treatment 10

15. Craneo-Caudal Medio-Lateral CraniocaudalMediolateral

16. Patient mammogram BIRAD 5

17. What should the primary physician do? -Radiologist A. Refer to surgeon for biopsy B. Refer for chest x-ray and bone scan C. Give antibiotics D. Removal of breast without biopsy E. Send home with pain medicines 10

18. Surgeon’s checklist Need to order mammogram if not already done Need to confirm diagnosis with tissue biopsy Remember to order receptors estrogen, progesterone, Her2-neu and Ki-67 Consider staging tests for locally advanced disease

19. What kind of biopsy would you do? Surgeon A. Core-needle biopsy B. Fine-needle aspiration C. Excisional biopsy D. Punch biopsy E. None of the above 10

20. Tissue –Sent to Pathologist Information given: -Breast “lump” -Do receptors (estrogen, progesterone, Her2-neu, Ki-67) Is this enough information for the pathologist?

21. Normal breast (skin, fat, breast tissue)

24. Hyperplasia with calcifications: Hematoxylin & Eosin

25. Ductal infiltrating carcinoma

26. Estrogen Receptor

27. Progesterone Receptor

28. Pathology Report: -Infiltrating Ductal Carcinoma Grade III some areas of in situ cancer -Estrogen and progesterone receptors negative, HER2- neu not amplified, Ki-67 25%

29. Breast Cancer Subtypes SubtypePathologyPrevalenceCharacteristics Luminal AER and/or PR + HER2- Low Ki67 Grade 1-2 30-70%-Best prognosis -Fairly high survival rates -Fairly low recurrence rates Luminal B-ER and/or PR + -HER2+ or HER2- and high Ki67 -Higher tumor grade -Larger tumor size -More often node+ 10-20%-Prognosis good, but -Survival not as high as luminal Triple negative (basal-like) ER and PR- HER2- 15-20%-Aggressive -Poorer prognosis in first 5 years HER2 TypeER and PR- Typically HER2+ 5-15%-Younger age -Outcome improved with introduction of anti-HER2 agents

30. What investigations would you do to complete the staging?- Radiologist Laboratories? CXR Chest CT? Abdominal ultrasound? Abdominal CT scan? CT scan brain? Bone scan? PET scan? Please discuss

31. Patient Summary-Radiology Mammogram right breast normal 6x8cm mass left breast – highly suspicious for malignancy BIRAD 5 Pathology reports infiltrating ductal carcinoma, high grade(III) ER and PR negative, Her2-neu not amplified (triple negative) Staging studies negative

32. MS Case Summary-Medical Oncology Mammogram right breast normal 6x8cm mass left breast – highly suspicious for malignancy BIRAD 5 Pathology reports infiltrating ductal carcinoma, high grade ER, PR negative, Her2-neu not amplified (Triple negative) Staging studies negative Clinical Stage: T3 N2 M0

33. What do you think should be done? Medical Oncologist A. Radical mastectomy B. Modified radical mastectomy C. Referral to medical oncology for neoadjuvant treatment D. Referral to radiation oncology for pre- operative external beam radiation E. Palliative care 10

34. Discussion – case summary Mammogram right breast normal 6x8cm mass left breast – highly suspicious for malignancy BIRAD 5 Pathology reports infiltrating ductal carcinoma, high grade ER, PR negative, Her2-neu not amplified (Triple negative) Staging studies negative Clinical Stage: T3 N2 M0 (Stage III)

35. Tumor Conference Treatment Plan: Neoadjuvant treatment Salvage mastectomy External radiation therapy Suppressive endocrine therapy ?? Follow up

36. Medical Oncologist’s thoughts, goals Healthy 52 year old woman with locally advanced breast cancer, triple negative, disease still seems localized to the breast and axilla. Neoadjuvant treatment (chemotherapy prior to surgery) will reduce tumor size and allow a mastectomy or perhaps a lumpectomy in selected cases. In Fact post AC4 +T4 tumour size went down to 2x2 cm. T1yNxMx.

37. Medical Oncologist’s thoughts MS does not qualify for post-operative endocrine therapy (Tamoxifen or aromatase inhibitors) because as her tumor was ER/PR negative She does not qualify for anti-HER2-neu therapy as her tumor was HER2 negative.

38. Survival According to Treatment: Stage III Treatment No. of Patients 5-Year Survival Surgery only2,45336% Radiation only2,38629% Surgery plus radiation4,24933% Chemotherapy, Surgery, and Radiation 1,92363% Giordiano SH. Oncologist. 2003;8:521-530.