Impact of BRCA mutation status on tumor infiltrating lymphocytes (TILs), response to treatment, and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

Abstract

Introduction: Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly BRCA pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to BRCA 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 BRCA 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 BRCA-deficient and 221 BRCA-proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in BRCA-deficient BC (p= 0.001), and this association remained statistically significant only in the luminal BC subtype (p= 0.006). The interaction test between BC subtype and BRCA status was nearly significant (Pinteraction=0.056). Pre and post-NAC TILs were not significantly different between BRCA-deficient and BRCA-proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in BRCA-deficient BC. Survival analysis were not different between BRCA-carriers and non-carriers. Conclusion: BRCA mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC. BRCA-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.

The Prognostic Value of Lymph Node Involvement after Neoadjuvant Chemotherapy Is Different among Breast Cancer Subtypes

“…With the widespread routine use of NAC for TNBC and HER2 -positive BC patients 1 2 , second-line trials in the post neoadjuvant setting for high risk patients are increasing testing the addition of chemotherapy, PARP inhibitors [ 36 ], immunotherapy [ 37 ], cyclin-dependent kinase inhibitors [ 38 ], or vaccines [ 39 ]. We previously demonstrated that TILs-enriched luminal BRCA tumors [ 40 ] and TILs-enriched HER-positive BC tumors are at a high risk of relapse [ 41 ] and could benefit from additional therapies. In the light of these current scientific developments, residual axillary disease is not a predictive factor of the efficacy of such specific therapies, but our findings are of particular importance since they may help to identify more accurately the high-risk patients who might benefit from such treatments by considering the number of residual positive nodes after NAC as a cornerstone of prognostication, provided that it is interpreted according to histological BC subtype.…”

Tumor‐Infiltrating Lymphocytes in Patients With Advanced Laryngeal Cancer Undergoing Bioselection

“…Traditional chemotherapy and radiation treatments have been shown to alter the immune system in head and neck cancer, and TILs have been shown to be predictive of response to neoadjuvant therapy in other tumor types, such as breast cancer. 20-22 Given the evidence of immunomodulatory effects of chemotherapy, we hypothesized that TILs may serve as a predictive biomarker for patients who would ultimately respond to induction chemotherapy. We therefore wished to investigate the role of TILs in predicting response to induction chemotherapy and OS in a cohort of patients undergoing chemotherapy bioselection at our institution.…”