Surgical treatment of BRCA mutated patients. Viviana Galimberti MD European Institute of Oncology Milan, Italy

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1 Surgical treatment of BRCA mutated patients Viviana Galimberti MD European Institute of Oncology Milan, Italy

2 No pharmaceutical company funding was used I declare I have no conflicts of interest as regards this presentation

3 BRCA-mutation carriers Healthy women Operable breast cancer Breast cancer survivors

4 BRCA-mutation carriers Healthy women

5 BRCA-mutation carriers RISK REDUCTION OPTIONS SURVEILLANCE AND LIFESTYLE MODIFICATION PHARMACOPREVENTION PROPHYLACTIC SURGERY

6 Woman s preference Importance of counselling Dealing with a risk and not a disease (not surgical alternatives) Selection of patients (benefit BRCA1 >BRCA2, breast dimension)

7 DISADVANTAGES ADVANTAGES Decreases risk Reduces anxiety Aesthetic satisfaction A major operation Irreversible Risk not completely abolished Early /late complications Loss of sensitivity Aesthetic result may not satisfy (depending on anatomy and expectations)

8 Autonomous informed decision Non autonomous or hasty decision

9 BRCA-mutation carriers Operable breast cancer

10 Main questions 1. Is breast conserving treatment (BCT) better or worse than unilateral mastectomy? 2. Does bilateral mastectomy offer additional advantages relative to BCT/ unilateral mastectomy? 3. Can we identify subgroups of pts. who will benefit from more aggressive treatment?

11 1. Risk of IBR after BCT: BRCA mutation carriers vs non carriers META ANALYSIS of 10 studies BRCA carriers IBR 17.3% (95% CI %) Non carriers IBR 11% (95% CI %) No difference in IBR risk after median follow up <7yrs RR 1.38 (95% CI , p = 0.51) Significantly greater IBR risk with median follow up 7yrs RR 1.51 (95% CI , p = 0.003) No difference between BRCA1 and BRCA2 carriers Two factors found protective against IBR: o Use of chemotherapy o Oophorectomy Valachis A 2014 Breast Cancer Res Treat

12 1.Risk for IBR in BRCA mutation carriers: Mastectomy versus BCT pts who underwent BCT had higher risk for IBR than pts with MASTECTOMY 15 yr cumulative risk 23.5% vs. 5.5% (p < ) However BCSS and OS were similar 15 yrs: 93.5% vs 92.8% 91.8% vs 89.9% Pierce LJ 2010 Breast Cancer Res Treat

13 1.Risk for IBR in BRCA mutation carriers: Mastectomy versus BCT pts who underwent BCT had higher risk for IBR than pts with MASTECTOMY 15 yr cumulative risk 32% vs 9% In univariable analysis HR 4.0 (95% CI ) In multivariate* analysis HR 2.9 (95% CI ) *adjusted for tumor stage, age and use of (neo)adjuvant CT However no significant difference in BCSS, OS or Distant Metastases Nilson MP Breast Cancer Res Treat

14 2.Risk of contralateral cancer (CBC): BRCA mutation carriers vs. non carriers Meta analysis of 11 studies BRCA mutation carriers had higher CBC risk than non carriers RR 3.56 (95% CI , p < 0.001) BCRA1 carriers had higher risk of CBC than BRCA2 carriers RR 1.42 (95% CI , p = 0.04) Two factors found to reduce risk of CBC: Oophorectomy Use of Tamoxifen Use of adjuvant CT DID NOT alter risk Valachis A Breast Cancer Res

15 2.BCSS and OS after contralateral prophylactic mastectomy (CPM) vs. therapeutic mastectomy NO difference in BC specific survival (HR 0.78, 95% CI ) Significant difference in OS 94% for CPM vs. 77% therapeutic mastectomy (p = 0.003) However after adjustment for prophylactic oophorectomy, the effect of CPM on OS was no longer significant (HR for event 0.35, p = 0.14) Valachis A Breast Cancer Res

16 LARGEST STUDY SO FAR REPORTED AT ASCO 2013 Significantly better OS in pts who had prophylactic mastectomy compared with those without mastectomy 10 yr OS 90% vs 80% However more pts in the prophylactic mastectomy group received CT Heemskerk Gerristen B. JCO 2013

17 3. Can we identify subgroups of pts. who will benefit from more aggressive treatment? According to the meta analysis of Valachis A Two factors associated with decreased risk of IBR: Use of adjuvant TAM Oophorectomy It was therefore suggested that in who do not receive oophorectomy more aggressive surgical approach to the breast might be appropriate

18 3. Can we identify subgroups of pts. who will benefit from more aggressive treatment? According to the meta analysis of Valachis A Three factors associated with decreased risk of CBC: Use of adjuvant TAM Oophorectomy Late age at first breast cancer diagnosis It was therefore suggested that in younger carrier pts who do not have oophorectomy and do not receive TAM a more aggressive surgical approach to the breast might be appropriate

19 CONCLUSIONS: CARRIER WITH OPERABLE BC This review of the data will remind clinicians of points to be included in the discussion with the patient before the final decision is made The discussion should mention evidence on oncological safety of conservative surg. 3.5 fold increase risk of CBC psychological aspects related to prophylactic mastectomy presence of factors that alter risks of IBR and CBC

20 BRCA-mutation carriers Breast cancer survivor

21 The considerations illustrated for the patient with a BC diagnosis, also apply to the survivor, but now there is more time to make a decision

22 WHEN THE DECISION IS FOR PROPHYLACTIC MASTECTOMY WHAT TYPE OF MASTECTOMY?

23 Is nipple sparing mastectomy (NSM) safe for women with BRCA mutations? A modern NSM aims to remove as much breast tissue as possible it is not a subcutaneous mastectomy. In general all breast tissue up to the base of the nipple (and often including a core of tissue within the nipple) is removed Done appropriately, NSM only differs from the now well accepted skin sparing mastectomy in that it preserves the areolar skin and the nipple skin.

24 How often is this tissue (NAC) involved with cancer recurrence or with new cancer development? Yao et al. summarized the available data on regarding nipple recurrence after NSM Large series of NSM have now been reported Low rates of recurrence overall Of 3,000 patients, <1 % developed NAC recurrence.

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