Molecular Analysis Finds A Subtype Triple-Negative Breast CA Chemosensitive
HealthDay News — For patients with triple-negative breast cancer (TNBC), a BRCA-deficiency (BRCA-D) subtype is chemosensitive, according to a study published online in PLOS Medicine.
Tingting Jiang, PhD, from Yale University in New Haven, Connecticut, and colleagues performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) with pathologic complete response (18 patients) or extensive residual disease (11 patients) after neoadjuvant chemotherapy. Data were included from two validation cohorts: 144 cases from The Cancer Genome Atlas (TCGA) and 278 cases from METABRIC.
The researchers found that mutations in the AR- and FOXA1-regulated networks, which involved BRCA1, correlated with significantly higher sensitivity to anthracycline/taxane chemotherapy in the MDACC cohort and significantly better survival outcome in the TCGA TNBC cohort. Tumors of a distinct BRCA-D TNBC subtype were identified; the subtype was characterized by low levels of wild-type BRCA1/2 expression. Significantly better survival was seen with standard-of-care chemotherapy for patients with functionally BRCA-D tumors versus tumors that were not BRCA-D; they also had significantly higher mutation burden and presented clonal neoantigens that correlated with increased immune cell activity. A transcriptional signature of BRCA-D TNBC tumors that correlated with improved survival in the METABRIC dataset was independently validated.
"The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in TNBC," the authors write.
One author disclosed financial ties to Nuvera Biosciences.