A Background on TNBC and Management

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Tiffany Traina, MD: Triple-negative breast cancer [TNBC] is defined by the lack of staining for estrogen receptor, progesterone receptor, and HER2. And historically this breast cancer has had a much higher risk of recurrence than its other biologic counterparts. That recurrence tends to happen rather quickly, in the first 2 to 3 years after an initial diagnosis. And the site of metastatic disease is often in visceral organs and can even be the brain. So it traditionally has the more aggressive phenotype associated with it. Once metastatic triple-negative breast cancer is diagnosed, with our current available therapies, median progression-free survival is considered about 4 months, and median overall survival is about a year.

There are many different classifications of triple negative breast cancer. I think we’ve—as a research community—come to recognize that there’s tremendous heterogeneity within this catch-all phrase of tripl- negative breast cancer. So 1 important advance is recognizing different molecular signatures that might then help divide out different drivers that could offer targeted therapies for those patients. For example, the molecular classifications that subdivide TNBC into basal light breast cancer, luminal androgen receptor—driven breast cancer, or immunomodulatory subsets are all reflecting heterogeneity in the underlying biology.

Until recently our standard-of-care treatment for metastatic triple-negative breast cancer has been limited to cytotoxic chemotherapy. While much of the molecular classifications have been encouraging, they are really still limited to the investigational setting. And so our standard of care remains chemotherapy. We have not yet had, until now, a specific targeted therapy driven by biology for triple negative breast cancer. One area that has been actionable, which is peripherally related to triple negative breast cancer, is that of germline BRCA mutations: BRCA1 or BRCA2. So there is overlap between germline BRCA1 pathogenic mutations and a diagnosis of triple negative breast cancer. In that setting we have 2 FDA-approved agents for germline BRCA-mutant associated breast cancer, including olaparib and talazoparib. But that has really been the limiting targeted therapy so far.

Transcript Edited for Clarity