Survival Outcomes by Mutation Status in Metastatic Breast Cancer.

PURPOSE

We sought to determine the significant genomic alterations in patients with metastatic breast cancer (MBC), and survival outcomes in common genotypes.

PATIENTS AND METHODS

High-depth next generation sequencing was performed for 202 genes in tumor and normal DNA from 257 patients with MBC, including 165 patients with ER/PR+ HER2- (hormone receptor positive, HR+ positive), 32 patients with HER2+ and 60 patients with triple negative (ER/PR/HER2-) cancer. Kaplan Meier survival analysis was performed in our discovery set, in breast cancer patients analyzed in The Cancer Genome Atlas, and in a separate cohort of 98 patients with MBC who underwent clinical genomic testing.

RESULTS

Significantly mutated genes (SMGs) varied by histology and tumor subtype, but was a SMG in all three subtypes. The most SMGs in HR+ patients included (32%), (29%), (15%), (8%), (8%), (5%), (4%), (4%), and (4%). mutations were associated with shorter recurrence-free survival (P=0.004), progression-free survival (P=0.00057) and overall survival (P=0.003). Further, status was prognostic among HR+ patients with mutations. mutations were also associated with poorer overall survival in the 442 HR+ breast cancer patients in the TCGA (P=0.042) and in an independent set of 96 HR+ MBC who underwent clinical sequencing (P=0.0004).

CONCLUSIONS

SMGs differ by tumor subtype but is significantly mutated in all three breast cancer subtypes. mutations are associated with poor prognosis in HR+ breast cancer. mutations should be considered in the design and interpretation of precision oncology trials.