Researchers ID Subtype of Triple Negative Breast Cancer That Responds Better to Chemotherapy

December 14, 2016

NEW HAVEN, Conn -- December 14, 2016 -- Researchers have identified a new subtype of triple negative breast cancer (TNBC) that shows significantly improved response to chemotherapy.

Patients with the newly defined “BRCA deficient” subtype experienced better survival with chemotherapy, according a study published in PLOS Medicine.

In the era of personalised cancer therapy, patients with TNBC remain at considerably higher risk of relapse and death than patients with other breast cancer subtypes, due to the aggressive nature of TNBC and the lack of newer targeted therapies for the disease.

For the study, researchers performed whole exome sequencing on TNBC tumours to identify mutations in specific genes or pathways that may indicate response or resistance to the standard of care, which is anthracycline/taxane (ACT) chemotherapy.

The researchers found that tumours carrying mutations in the AR and FOXA1 pathways had a significantly higher response rate (94.1%) compared with tumours without the mutations (16.6%).

Analysis of genomic, epigenetic, and RNA sequencing data revealed that the combinations of mutations that lowered the levels of functioning BRCA1 and BRCA2 RNA were associated with significantly better survival outcomes.

“Low levels of functional BRCA are associated with a greater number of clonal mutations and enhanced immune recruitment, which may explain the greater chemosensitivity of these tumours and better outcomes for patients,” said senior author Christos Hatzis, Yale Cancer Center, New Haven, Connecticut.

“The strong connection of ACT chemosensitivity and immune activity in the newly defined BRCA-deficient phenotype of TNBC could help inform future therapeutic strategies for our patients,” said Lajos Pusztai, MD, Yale Cancer Center.

SOURCE: Yale Cancer Center

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