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Purpose: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing., Methods and Materials: We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest wall RT with or without regional nodal irradiation, multigene panel testing, and evaluation at a large cancer center's genetic screening program. We evaluated rates of overall survival, locoregional recurrence, disease-specific death, and radiation-related toxicities in 3 groups: BRCA1/2 PV carriers, non-BRCA1/2 PV carriers, and patients without PV mutations., Results: PVs were detected in 25.2% of the cohort (12.6% BRCA1/2 and 12.6% non-BRCA1/2). The most commonly detected non-BRCA1/2 mutated genes were ATM, CHEK2, PALB2, CDH1, TP53, and PTEN. The median follow-up time for the entire cohort was 4.4 years (95% confidence interval, 3.8-4.9 years). No differences were found in overall survival, locoregional recurrence, or disease-specific death between groups (P > .1 for all). Acute and late toxicities were comparable across groups., Conclusion: Oncologic and toxicity outcomes after RT in women with PV germline mutations detected by multigene pane testing are similar to those in patients without detectable mutations, supporting the use of adjuvant RT as a standard of care when indicated., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: BRCA1/2 pathogenic variant (PV) mutations confer radiation sensitivity preclinically, but there are limited data regarding breast cancer outcomes after radiation therapy (RT) among patients with documented BRCA1/2 PV mutations versus no PV mutations., Methods and Materials: This retrospective cohort study included women with clinical stage I-III breast cancer who received definitive surgery and RT and underwent BRCA1/2 genetic evaluation at the The University of Texas MD Anderson Cancer Center. Rates of locoregional recurrence (LRR), disease-specific death (DSD), toxicities, and second cancers were compared by BRCA1/2 PV status., Results: Of the 2213 women who underwent BRCA1/2 testing, 63% self-reported their race 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; and 1394 (63%) received regional nodal RT. The median follow-up time for all patients was 7.4 years (95% confidence interval [CI], 7.1-7.7 years). No differences were found between the groups with and without BRCA1/2 PV mutations in 10-year cumulative incidences of LRR (with mutations: 11.6% [95% CI, 7.0%-17.6%]; without mutations: 6.6% [95% CI, 5.3%-8.0%]; P = .466) and DSD (with mutations: 12.3% [95% CI, 8.0%-17.7%]; without mutations: 13.8% [95% CI, 12.0%-15.8%]; P = .716). On multivariable analysis, BRCA1/2 status was not associated with LRR or DSD, but Black/African American patients (P = .036) and Asians/American Indians/Alaska Native patients (P = .002) were at higher risk of LRR compared with White patients, and Black/African American patients were at higher risk of DSD versus White patients (P = .004). No in-field, nonbreast 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 patients with breast cancer who had a germline BRCA1/2 PV mutation and were treated with RT were similar to those of patients with no mutation, supporting the use of RT according to standard indications in patients with a germline BRCA1/2 PV mutation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The impact of regional nodal irradiation (RNI) on locoregional recurrence (LRR) and any disease recurrence (DR) in women with node-positive breast cancer who receive neoadjuvant systemic therapy (NAT) is unknown., Methods and Materials: The impact of RNI on LRR and DR was estimated with the cumulative incidence method in 1289 women with stage II to III breast cancer with cytologically confirmed axillary metastases who received NAT between 1989 and 2007. Multicovariate Cox regression analysis was performed to examine the effect of RNI after accounting for other predictive and prognostic variables., Results: The median follow-up after definitive surgery was 10.2 years. Axillary pathologic complete response (pCR) was observed in 368 of 1289 patients (28.5%). On univariate analysis, axillary pCR reduced 10-year LRR risk from 9.7% to 4.8% (P = .006) and DR risk from 43.0% to 17.0% (P < .001). RNI was administered to 1080 of 1289 patients (83.8%). On univariate analysis, RNI did not affect 10-year LRR risk (no RNI, 9.4%; RNI, 8.1%; P = .62) or DR risk (no RNI, 31.3%; RNI, 36.5%; P = .16). On multicovariate analysis, RNI significantly reduced the risk of LRR (hazard ratio, 0.497; 95% confidence interval [CI], 0.279-0.884; P = .02) and DR (hazard ratio, 0.731; 95% CI, 0.541-0.988; P = .04) and showed a particularly strong reduction in risk of DR in patients with HER2+ disease who received trastuzumab (hazard ratio, 0.237; 95% CI, 0.109-0.517; P = .0003). A nomogram to predict 10-year LRR risk with and without RNI has been generated to assist clinicians in individualizing treatment decisions based on patient and disease characteristics and response to NAT., Conclusions: Adjuvant RNI reduces risk of LRR and DR in patients with breast cancer with axillary metastases who receive NAT across subtypes and particularly decreases the risk of DR in HER2+ breast cancer treated with trastuzumab. Enrollment on the National Surgical Adjuvant Breast and Bowel Project B-51/Radiation Therapy Oncology Group 1304 protocol is encouraged to help determine whether RNI can be omitted in patients with axillary pCR to NAT., (Copyright © 2018 Elsevier Inc. All rights reserved.)