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Germline DNA Repair Mutations and Prognosis in Castration-Resistant Prostate Cancer

By: Kayci Reyer
Posted: Thursday, January 31, 2019

According to a study published in the Journal of Clinical Oncology, mutations in the BRCA2 gene seem to negatively affect outcomes in patients with metastatic castration-resistant prostate cancer. In fact, this research indicates the outcomes linked to this genetic mutation may be modified by the type of initial treatment.

“These mutations should be identified in patients with metastatic prostate cancer, since detecting such alterations is important for the diagnosis and management of the disease and for the patients’ families, whose risk of developing breast, ovarian, or pancreatic cancer is increased,” explained Elena Castro, MD, PhD, of the Spanish National Research Centre, in a press release to the Centro Nacional de Investigaciones Oncológicas in Madrid.

Of the 419 patients enrolled in the prospective cohort study PROREPAIR-B, 68 (16.2%) were identified as carriers of germline DNA damage repair gene mutations. Overall, 14 participants (3%) had BRCA2 mutations, specifically, which were found to be an independent prognostic factor of cause-specific survival (hazard ratio = 2.11; P = .33). Germline BRCA2 carriers experienced cause-specific survival that was half that of noncarriers (17.4 vs. 33.2 months; P = .027), whereas the overall cause-specific survival comparison between all carriers and noncarriers was not statistically significant (23.3 vs. 33.2 months; P = .264).

Survival outcomes varied for BRCA2 carriers based on first-line treatment. Patients treated with first-line abiraterone or enzalutamide experienced greater cause-specific survival (24 vs. 17 months) and progression-free survival (18.9 vs. 8.6 months) compared with patients treated with taxanes. Noncarriers did not see different clinical outcomes based on treatment type.

Disclosure: The study authors’ disclosure information may be found at ascopubs.org.



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