The optimal local management of early-stage breast cancer in BRCA-mutation carriers remains a matter of debate. These patients are facing the difficult question to choose among breast-conserving therapy (BCT), unilateral mastectomy or prophylactic bilateral mastectomy.
The purpose of this meta-analysis is to investigate the oncological safety of BCT in BRCA-mutation carriers and the risk for contralateral breast cancer (CBC) compared with non-carriers, to identify potential risk or protective factors for ipsilateral breast recurrence (IBR) or CBC and to grade these factors based on the level of evidence.
A PubMed search was conducted through March 2013 to identify studies that described the risk for IBR and CBC after BCT in BCRA-mutation carriers versus non-carriers as long as studies that investigated risk/protective factors for IBR and CBC in BRCA-mutation carriers. We collated the risk/protective factors into four levels of evidence (high, moderate, low, inconclusive), depending on consistency of findings and quality and quantity of studies contributing to findings. For each risk factor, we abstracted odds ratios (ORs), hazard ratios (HRs), or risk ratios (RRs) and associated 95% Confidence Intervals (CIs), based only on adjusted estimates obtained from multivariate analyses. Results were summarized by using meta-analysis when sufficient studies were available.
Ten studies (7 cohort and 3 case-control; 2826 patients) investigated the oncological safety of BCT in BRCA-mutation carriers versus non-carriers. There was no significant difference in IBR between carriers and controls (RR: 1.45, 95% CI: 0.98-2.14, p-value = 0.07). However, CBCs were significantly greater in carriers versus controls (RR: 3.56, 95% CI: 2.50 – 5.08, p-value < 0.001) (11 studies; 3970 patients). Patients with BRCA-1 mutation had a higher risk of CBC than patients with BRCA-2 mutation (RR: 1.42, 95% CI: 1.01-1.99, p-value = 0.04). Use of adjuvant chemotherapy (HR: 0.51, 95% CI 0.31-0.84) and oophorectomy (HR: 0.42, 95% CI 0.22-0.81) were associated with a significantly lower risk for IBR in BRCA-mutation carriers, with a moderate level of evidence, while use of tamoxifen did not significantly alter the risk. Three factors were associated with a lower risk of CBC in BRCA-mutation carriers: oophorectomy (moderate level of evidence), use of tamoxifen (moderate level of evidence), and age at first breast cancer (decreased incidence of CBC with increasing age; high level of evidence).
Based on current evidence, the use of BCT in BRCA-mutation carriers can be considered a reasonable option since it does not seem to increase the risk of IBR. However, several aspects should be taken into account before the final decision-making, including the 3.5-fold increased risk for CBC and the presence of several factors that can alter the risk of IBR and CBC. The identification of these risk factors may be useful in the discussion on the different surgical treatment options with these patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-06.