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'High Frequency' of Germline Mutations Found in Patients With Metastatic Breast Cancer - Cancer Therapy Advisor

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Patients with metastatic breast cancer have a “high frequency” of germline mutations in BRCA1/2 and other breast cancer predisposition genes, researchers reported in the Journal of Clinical Oncology.

The mutation rates for breast cancer predisposition genes were determined using germline DNA from 2595 patients with metastatic breast cancer who were enrolled in the prospective PRAEGNANT registry (ClinicalTrials.gov Identifier: NCT02338167).

In all, 271 patients (10.4%) had germline mutations in 12 established breast cancer predisposition genes, and 129 patients (5%) had BRCA1/2 mutations specifically.


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The researchers compared the mutation rate in this group to the mutation rate in a cohort of patients with nonmetastatic breast cancer. The mutation rate was significantly higher in the metastatic cohort than in the nonmetastatic cohort — 10.4% and 6.6%, respectively (P <.01).

Based on this finding, the researchers suggested that mutations in specific genes may promote the progression from early-stage breast cancer to metastatic breast cancer. 

The researchers also found that brain metastasis was more common in BRCA1 mutation carriers than in noncarriers — 27.1% and 12.8%, respectively. The association between BRCA1 and brain metastases was mainly seen in patients with triple-negative breast cancer.

The presence of mutations did not have a significant effect on progression-free survival or overall survival in patients with metastatic breast cancer. Although mutation carriers and noncarriers displayed differences in tumor characteristics, there were no differences in prognosis.

“Multigene panel testing may be considered in all patients with mBC [metastatic breast cancer] because of the high frequency of germline mutations in BRCA1/2 and other BC [breast cancer] predisposition genes,” the researchers wrote. “Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and future studies of targeted therapies.”  

Disclosures: This research was supported by Novartis, Celgene, Pfizer, the National Institutes of Health, and the Breast Cancer Research Foundation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Fasching PA, Yadav S, Hu C, et al. Mutations in BRCA1/2 and other panel genes in patients with metastatic breast cancer — association with patient and disease characteristics and effect on prognosis. J Clin Oncol. 2021;39(15):1619-1630. doi:10.1200/JCO.20.01200

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