Risk-reducing surgery in BRCA 1/2 mutation carries: a point of view

BRCA1/2 mutation identifies healthy women who are at 5 to 20 fold increased risk for future development of ovarian cancer (OC) and breast cancer (BC) [1]. In general, BRCA 1 mutation carriers have an elevated lifetime risk of BC (65-85 %) and a slightly lower associated lifetime risk of OC (20-50%); whereas in BRCA 2 mutation it is reported an OC incidence of 10-15 % and a similar BC risk as BRCA 1 [1]. We would like to provide a reliable evaluation of the effect of risk-reducing surgery, both salpingo-oophorectomy (RRSO) and bilateral mastectomy (BRRM), to reduce long-term onset of ovarian cancer OC and/or BC in BRCA 1 / 2 mutation carriers. Considering the recent two meta-analysis [2-3], a strong efficacy of RRSO and BMMR strategies in OC and BC risk-reduction has been respectively confirmed (80% and 94%). Adding new data did not change the magnitude of the known impact of RRSO on OC risk reduction [4], as well as BMMR on BC [5], whereas it was demonstrated the benefit of BMMR also for those patients who received both surgical procedures. Consequently these results should be useful to determine standard risk-reduction management in this setting of patients, as well as generating new hypotheses to be proposed in clinical practice. Three separate questions can be raised to address the variety of approach: firstly, the choice of both risk-reducing surgies in patients with BRCA 1 / 2 mutation, secondly the optimal timing in performing surgical strategies and lastly the cost-effectiveness of prophylactic surgery. Regarding the first question, because of RRSO decreases the risk of OC by 80% and also reduces the risk of BC up to 50%, nowadays, it is recommended by the age of 40 years after the completion of childbearing [6]. But the residual BC risk in post-RRSO women remains still higher (up to 40%) than that in general population [3]. This residual risk, in addition to the absolute higher lifetime risk of BC than OC (56-84% versus 10-46%) and the evidence that BRRM nearly eliminates the risk of BC, should be considered sufficient to justify BRRM. In addition, we have no randomized data that compared survival benefit between BRRM and screening regimens. Importantly, there was a Monte Carlo simulation model suggesting prophylactic surgeries as cancer risk-reducing options [7]. Breast screening plus RRSO appeared to yield lower survival probability (6% and 3% in BRCA1 and BRCA2, respectively) with an increase …