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William J. Gradishar, MD, FACP, FASCO


ASTRO 2023: Impact of BRCA1/2 Mutations on Outcomes Following Radiotherapy

By: Celeste L. Dixon
Posted: Monday, October 16, 2023

Although laboratory work has demonstrated that BRCA1/2 mutations in isolated cancer cells can enhance those cells’ radiosensitivity, the mutations do not seem to predict improved survival for real-world patients with breast cancer who have received radiation therapy. After analyzing a large, previously unexamined national data set and taking into account the later stage at which BRCA1/2-mutated tumors are often found, Zachary Kiss, DO, of Fox Chase Cancer Center, Philadelphia, and colleagues concluded that “the effect of BRCA1/2 mutations on radiosensitivity in vitro may be nullified by the aggressive behavior of BRCA1/2-mutated tumors in vivo.” They reported their findings of no differences in survival outcomes in patients with mutated versus wild-type BRCA1/2 at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 2443).

The team set out to analyze a de-identified national database of 1,561 patients with stage 0 to III breast cancer from the Flatiron Health electronic health record to determine whether patients with BRCA1/2 mutations (n = 79) receiving radiation therapy achieved longer survival than those with wild-type BRCA genes (n = 1,482). Patients with known BRCA1/2 status were eligible if they were treated with radiation therapy within 1 year of diagnosis. Of the 79 patients with mutations, 31 and 46 patients had BRCA1 and BRCA2 mutations, respectively, and 2 patients had both.

When compared with patients with wild-type BRCA, those with BRCA1/2 mutations had tumors diagnosed at a higher clinical stage (P = .016) and that were more often grade III (P < .001); they were also more likely to undergo mastectomy (60.8% vs. 31.5%; P < .001). Patients with BRCA1/2 mutations were also younger (median age, 51 vs. 56 years; P = .004).

Disclosure: No disclosure information was provided for the study authors.

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