breast cancer

Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer —Association With Patient and Disease Characteristics and Effect on Prognosis

Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer —Association With Patient and Disease Characteristics and Effect on Prognosis

Background and purpose

Patients with metastatic breast cancer, have a relatively small but impactful prevalence of germline mutations in cancer susceptibility genes.  In the reported study, a prospectively followed cohort of patients with metastatic breast cancer was used to determine mutation rates for breast cancer predisposition genes.  Furthermore, clinical characteristics were evaluated in patients with these mutations to determine if there is any influence on patient outcome.

Patients and methods 

2,595 patients with metastatic breast cancer were rolled in the prospective PREGNANT registry.  They were evaluated for the presence of cancer predisposition genes.  The frequencies of mutations in known breast cancer predisposition genes were compared with results from a cohort of patients that were also followed prospectively in the registry from nonmetastatic breast cancer sequenced using the same QIAseq method.  Public reference controls were used.  Mutation status was used to determine tumor characteristics, progression free survival and overall survival.

Results

Germline mutations in 12 predisposition genes were determined.  These included BRCA1 and BRCA2.  BRCA1 and BRCA2 was seen in one hundred and twenty-nine patients, 5%. The total number of detected predisposition genes was seen in two hundred seventy-one patients, 10.4%.  BRCA1 mutation carriers had a high propensity for brain metastases, 27.1%.  This is in comparison to nonmutation carriers, 12.8%.  Mutations were significantly enriched in the PREGNANT patients with metastatic breast cancer compared with patients with nonmetastatic breast cancer, 10.4% versus 6.6%, P < 0.01.  Important to note, that mutations did not significantly modify progression free survival or overall survival for patients with metastatic breast cancer.

Conclusion

The authors concluded that multigene panel testing may be considered for all patients with metastatic breast cancer. Even though the prognosis was similar in mutation carriers and nonmutation carriers of metastatic breast cancer, there are notable differences in tumor characteristics which may have implications for future treatment and studies.

https://ascopubs.org/doi/full/10.1200/JCO.20.01200

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