Stromal grading predicts pathologic complete response and prognosis in triple-negative breast cancer

Do traditional prognostic factors fully account for the diversity of clinical behavior in breast cancer? Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer seen to have a poor prognosis, although there is great variation in clinical outcomes. Most recently, novel approaches have targeted the tumoral microenvironment (TME) to determine prognosis and tumor-associated stroma has become increasingly recognized as a potential biomarker to predict treatment response and prognosis in TNBC. The principle aim of this paper is to demonstrate an approach to stromal grading in TNBC, with consideration of its utility for predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and clinical survival outcomes. We evaluated 152 TNBC cases from the Firehose Legacy TCGA Cohort and validated our findings in a series of 110 patients from our health system. Stromal grading correlated with clinical outcomes related to prognosis and response to NAC, advanced pathologic stage, as well as clinical demographics like age over 50 years with good interobserver reliability (83.6-89.1%). Looking forward, the TME could carve out a more precision-based care in TNBC and breast cancer generally.