Impact of Mutation Status on Tumor Infiltrating Lymphocytes (TILs), Response to Treatment, and Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

INTRODUCTION

Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to status.

MATERIAL AND METHODS

Out of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline pathogenic variant. We evaluated pre-NAC and post-NAC immune infiltration (TILs). Response to chemotherapy was assessed by pCR rates. Association of clinical and pathological factors with TILs, pCR and survival was assessed by univariate and multivariate analyses.

RESULTS

Among 1199 BC patients: 46 were -deficient and 221 proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in deficient BC ( 0.001), and this association remained statistically significant only in the luminal BC subtype ( 0.006). The interaction test between BC subtype and status was nearly significant ( = 0.056). Pre and post-NAC TILs were not significantly different between deficient and proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in deficient BC. Survival analysis were not different between carriers and non-carriers.

CONCLUSIONS

mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC. -carriers with luminal BCs may represent a subset of patients deriving higher benefit from NAC. Second line therapies, including immunotherapy after NAC, could be of interest in non-responders to NAC.