Outcomes after breast radiotherapy in a diverse patient cohort with a germline BRCA1/2 mutation.

Background BRCA1/2 pathogenic variant (PV) mutations confer radiosensitivity preclinically, but there is limited data regarding breast cancer patient outcomes following radiotherapy (RT) among those with documented BRCA1/2 PV vs. no PV. Methods This retrospective cohort study included women with clinical stage I-III breast cancer who received definitive surgery+RT and underwent BRCA1/2 genetic evaluation at the ***. Rates of locoregional recurrence (LRR), disease-specific death (DSD), toxicities, and second cancers were compared by BRCA1/2 PV status. Results Of the 2,213 women who underwent BRCA1/2 testing, 63% self-reported as white, 13.6% as Black/African American, 17.6% as Hispanic, and 5.8% as Asian/American Indian/Alaska Native; 124 had BRCA1 and 100 had BRCA2 mutations; 63% (1,394) received regional nodal RT. Median follow-up time for all patients was 7.4 years (95% CI 7.1–7.7 years). No differences were found in 10-year cumulative incidences of LRR or DSD between BRCA1/2 PV and no-mutation groups {(LRR: 11.6% [95% CI 7.0–17.6%] PV vs. 6.6% [95% CI 5.3–8.0%] no-mutation, p=0.466) and (DSD: 12.3% [95% CI 8.0–17.7%] PV vs. 13.8% [95% CI 12.0–15.8%] no-mutation, p=0.716)}. On multivariable analysis, BRCA1/2 status was not associated with LRR or DSD, but Black/African Americans (p=0.036) and Asians/American Indians/Alaska Natives (p=0.002) were at higher risk of LRR as compared to whites, and Black/African Americans were at higher risk of DSD vs. whites (p=0.004). No in-field, non-breast second cancers were observed in the BRCA1/2 PV group. Rates of acute and late grade ≥3 radiation-related toxicity in the BCRA1/2 PV group were 5.4% (n=12) and 0.4% (n=1), respectively. Conclusions Oncologic outcomes in a diverse cohort of breast cancer patients with a germline BRCA1/2 PV mutation treated with RT were similar to those with no mutation, supporting the use of RT according to standard indications in patients with a germline BRCA1/2 PV.