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Multi Disciplinary Cancer Management –Breast Cancer Dr Masalu N. MD Medical Oncologist 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 Breast Cancer Survival According to Stage at Diagnosis Medical Oncologist Stage 0 I II 5 year survival 100% 100% 93% III IV 72% 22% *NCI seercancer.gov Over 90% of US breast cancer cases present with localized or regional disease (nodes)* Most breast cancer cases in Tanzania present with stage IIIB or IV disease 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 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 Interdisciplinary Team Medical Oncologist Spiritual counselor Volunteers Nurse Family Physician Social Worker Patient Psychologist Community Pharmacist Physical therapist Hospice worker Malignant cancer cells can metastasize (spread Normal cells know : Neoplastic cells: • When to grow • How to differentiate • When to stop growing • When to die (apoptosis) • Grow too much • Do not differentiate • Do not stop growing • Do not die 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, HER2/neu, +/- Ki-67 status have documented clinical usefulness as tumor markers and choice of therapy Molecular profile (costly; limited access) Breast Cancer Subtypes Pathologist Subtype Pathology Prevalence Characteristics Luminal A ER and/or PR + HER2Low 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 PRHER2- 15-20% -Aggressive -Poorer prognosis in first 5 years HER2 Type ER and PRTypically HER2+ 5-15% -Younger age -Outcome improved with introduction of anti-HER2 agents Treatment of cancer is multidisciplinary Medical Oncologist Surgery Radiation Chemotherapy Targeted Therapy Gene Therapy Tumor removal DNA Damage DNA Disruption or damage Selective signal blocking Replacement of gene function FUTURE: Personalized therapy “Identify which therapy will be more successful for each patient” 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 glands Pregnancies 4 Deliveries 3 Menarche at age 12; last period at 50 Never had a breast biopsy swollen Family History • 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 • Vital signs: Temp 36.2 137/67 Pulse 89 Blood Pressure • A large 6x8 cm movable breast mass, without skin changes • Axilla: Several enlarged lymph nodes • Supraclavicular and cervical nodes: negative • Liver feels normal Should we order a mammogram?- Radiologist 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 A. 10 Mediolateral Medio-Lateral Craniocaudal Craneo-Caudal Patient mammogram BIRAD 5 What should the primary physician do? -Radiologist 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 A. 10 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 What kind of biopsy would you do? Surgeon A. B. C. D. E. Core-needle biopsy Fine-needle aspiration Excisional biopsy Punch biopsy None of the above 10 Tissue –Sent to Pathologist Information given: -Breast “lump” -Do receptors (estrogen, progesterone, Her2-neu, Ki-67) Is this enough information for the pathologist? Normal breast (skin, fat, breast tissue) Hyperplasia with calcifications: Hematoxylin & Eosin Ductal infiltrating carcinoma Estrogen Receptor Progesterone Receptor Pathology Report: -Infiltrating Ductal Carcinoma Grade III some areas of in situ cancer -Estrogen and progesterone receptors negative, HER2neu not amplified, Ki-67 25% Breast Cancer Subtypes Subtype Pathology Prevalence Characteristics Luminal A ER and/or PR + HER2Low 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 PRHER2- 15-20% -Aggressive -Poorer prognosis in first 5 years HER2 Type ER and PRTypically HER2+ 5-15% -Younger age -Outcome improved with introduction of anti-HER2 agents 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 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 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 What do you think should be done? Medical Oncologist Radical mastectomy B. Modified radical mastectomy C. Referral to medical oncology for neoadjuvant treatment D. Referral to radiation oncology for preoperative external beam radiation E. Palliative care A. 10 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) Tumor Conference Treatment Plan: Neoadjuvant treatment Salvage mastectomy External radiation therapy Suppressive endocrine therapy ?? Follow up 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. 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. Survival According to Treatment: Stage III No. of Patients 5-Year Survival Surgery only 2,453 36% Radiation only 2,386 29% Surgery plus radiation 4,249 33% Chemotherapy, Surgery, and Radiation 1,923 63% Treatment Giordiano SH. Oncologist. 2003;8:521-530.