Prevention and screening in brca mutation carriers for breast cancers

Prevention and screening in brca mutation carriers for breast cancers

1. Breast BRCA Mutation Prevention & Screening Presented by: Dr. Rahul Shah Medical Officer, BTFCC 11/4/2020

2. Lecture Outline 11/4/2020

3. Clinical Vignette of 50 Y/O F 5 months prior, noticed multiple lump in Rt. Breast but no consult on bhadra l.e . 2077/5/4 she went to district government hospital of sarhali : adviced for FNAC for which she visited another medical hospital where she had USG guided FNAC(2077/5/12) : suspicious malignant tissue . was adviced to visit cancer center but she visited general surgeon where she had Rt . Breast MRM on (2077/5/21) and specimen send for histo -pathology analysis HER histopathology report showed (21/9/2020):- I nvasive carcinoma of no special type(invasive ductal carcinoma , not otherwise specified) with glandular/tubular differentiation. 11/4/2020

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5. Chemo Regimen 11/4/2020

6. The Breast Anatomy and Physiology 11/4/2020

7. EMBRYOLOGY 5 TH TO 6 TH WEEK OF FETAL DEVELOPMENT MAMMARY RIDGES Each breast develops when an ingrowth of ectoderm forms a primary tissue bud in the mesenchyme. 15-20 SECONDARY BUDS: EPITHELIAL CORDS DEVELOP MAJOR DUCT DEVELOP- OPEN TO SHALLOW MAMMARY PIT INFANCY: MESENCHYME PROLIFERATES FORMING PIT TO NIPPLE 11/4/2020

8. FUNCTIONAL ANATOMY 11/4/2020

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10. Blood Supply 11/4/2020

11. Lymph supply 11/4/2020

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13. Lymph Drainage Name Drainage Lateral (Axillary Vein Group) Level I 75% drainage MC site of Axillary LN mets Anterior or pectoral (external mammary Group) Level I Lateral Aspect of the breast Posterior of Subscapular (Subscapular group ) Level I Lower posterior neck, the posterior trunk and the posterior shoulder Central Group (level II) Both axillary vein, external mammary and directly from the breast Apical (Sub clavicular Group) Level III From all of the other group of Axillary LN Interpectoral group (Rotter’s nodes) level II Directly to central and subclavicular groups 11/4/2020

14. Physiology 11/4/2020

15. PHYSIOLOGY OF BREAST Breast development and function Hormonal stimuli: Estrogen: ductal development Progesterone: differentiation of epithelium & lobular development Prolactin: primarily hormonal stimulus for lactogenesis in late pregnancy & the postpartum period. 11/4/2020

16. BRCA Mutation 11/4/2020

17. Angelina Jolie’s Decision 11/4/2020

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19. Familial Breast Cancer Approx. 12% due to inheritance of Identifiable Susceptibility Genes Probability increases with multiple affected first degree relatives, early onset Ca, Multiple Ca or Family members with other specific Ca. BRCA1 and BRCA2 are responsible for 80-90% of Single gene familial Breast Ca and overall 3% of all Ca. Frequency: 1 in 400 in general population, Genetic Testing is difficult and generally Restricted to high risks cases Identification of carriers is important, since Increased Surveillance, Prophylactic mastectomy, Salphingo -oophorectomy Can reduce Ca related mortality and morbidity. 11/4/2020

20. G ermline mutation in BRCA1 or BRCA2 results in a significantly elevated lifetime risk of developing breast and ovarian cancer, estimated at up to 7 and 25 times (respectively) that of the average risk population. 11/4/2020

21. BRCA Mutation = Increased Risk 11/4/2020

22. BRCA Mutation: Risk in Males 11/4/2020

23. Family History Consideration One half of BRCA carriers inherit mutation from their father Ovarian Ca is important indicator Early Onset Breast Ca is more important than the number of family members affected 11/4/2020

24. Considerations Triple – ve Breast Ca are more inclined to have BRCA mutation even without a family history. Testing is indicated if Triple – ve Breast Ca diagnosed before age of 60 Pancreatic Ca: If 2 or more family members affected, 17-19% families will have BRCA mutations 11/4/2020

25. Prevalence of BRCA mutations 11/4/2020

26. Genetic Testing 11/4/2020

27. Initial Counselling and Follow-UP of BRCA mutation Carriers Screening for early detection Risks reducing measures Issues Pertaining to Fertility in women who have not completed their family. Age >25 if not tested should be encouraged, if + ve should be counselled about risk reduction measures Until mutation status has been assessed and in women declining genetic testing or risk reduction measures, screening recommendations as for known mutation carriers should be followed . If available, carriers should be encouraged to participate in dedicated high-risk follow-up clinics that specifically focus on follow-up and screening of individuals with a known hereditary cancer syndrome 11/4/2020

28. Breast Cancer Risks Reduction 11/4/2020

29. Lifestyle Modifications 11/4/2020

30. Screening CBE in 6-12months after 25 10 years prior of earliest diagnosed case in family Breast Aware: Lump and Axilla Most sensitive: MRI-Annual screening After 30 MRI + Mammography annually USG as an alternative for MRI if not available 11/4/2020

31. RISK REDUCING AGENTS SERM and aromatase inhibitor as primary prevention (62%) According to studies tamoxifen has role in contralateral Ca prevention: 50% BRCA associated Ca should be treated as same like Non BRCA Ca 11/4/2020

32. RISK REDUCING SURGERIES most effective method for reducing breast cancer : Bilateral risk-reducing mastectomy (RRM ) by ∼90% SSM and NSM as alternatives followed by reconstruction NSM has higher risk for residual risk Contralateral risk-reducing mastectomy (CRRM) among patients with a previous breast cancer diagnosis can be considered. 11/4/2020

33. Reconstruction after Mastectomy 11/4/2020

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36. BRCA MALE SCREENING BRCA 1 BRCA 2 Consider Annual Clinical Breast exam from age 30 Consider Annual Clinical Breast exam from age 30 Prostate Ca Annual screening can be considered from age 40 11/4/2020

37. References Schwartz Textbook of Surgery 9 th Edition Robbins and Cortran Textbook of Pathologic Basis of Disease 9 th Edition ESMO Clinical Practice guidelines on prevention and screening in BRCA mutation Carriers and other Breast/Ovarian Heriditary Cancer Syndromes Brcacalculator.com Risk-Reducing Oophorectomy and Breast Cancer Risk Across the Spectrum of Familial Risk   Terryn et all 11/4/2020

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