The impact of loco-regional treatment on ipsilateral breast cancer recurrence and outcomes in carriers of BRCA1/2 pathogenic variants

Purpose: Our previous data showed that carriers of germline BRCA1/2 pathogenic variants (PV) with breast cancer (BC) treated with mastectomy without post-mastectomy radiation therapy (PMRT) had higher rates of loco-regional recurrence (LRR) compared to those who underwent PMRT or breast-conserving therapy (BCT), despite earlier stage BC. Our aim was to verify our previous findings in a larger cohort. Methods: Clinical data were extracted from the medical records of BRCA1/2 mutation carriers with BC, treated at a single institution between 1/2006 and12/2022. The data included demographics, treatment modalities, and BC outcomes. Results: A total of 464 patients with 484 primary tumors were analyzed. Of these, 48.3% mastectomies were performed: 66% (154) without PMRT (non-PMRT) and 34% (80) with PMRT; 51.8% (250) underwent BCT. The non-PMRT group had earlier disease stages at diagnosis (77.3% were Tis and T1N0 stage) compared to the PMRT and BCT groups (3.8% and 45%, respectively, p < 0.001). During the study period with a median follow-up time of 75 months (range 12–211), the LRR rate was 13% (20/154) in the non-PMRT cohort compared with 1.25% (1/80) in the PMRT group (p = 0.003), and 6.4% (16/250) in the BCT group (p = 0.03). Cumulative incidence of LRR at 5 and 15 years was 14.7%, and 16.6% in the non-PMRT, compared to 5.1% and 35% in the BCT group, respectively (p = 0.081). No significant difference in overall survival was observed (p = 0.202). Conclusions: The timing and rates of LRRs differ according to the loco-regional therapy, which might indicate a different etiology driving these events.