Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BACKGROUND: The non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers. AIMS: To evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis. METHODS: A systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method. RESULTS: Twenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I(2)) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I(2) = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I(2) = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I(2) = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I(2) = 38%) were equivalent for combined BCT and mastectomy. CONCLUSIONS: Survival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.