Association of Tumor-Infiltrating Lymphocytes with Homologous Recombination Deficiency and Status in Patients with Early Triple-Negative Breast Cancer: A Pooled Analysis.

Purpose: Patients with triple-negative breast cancer (TNBC) with homologous recombination deficient tumors achieve significantly higher pathologic complete response (pCR) rates when treated with neoadjuvant platinum-based therapy. Tumor-infiltrating lymphocytes (TIL) are prognostic and predictive of chemotherapy benefit in early stage TNBC. The relationship between TILs, mutation status, and homologous recombination deficiency (HRD) status in TNBC remains unclear.

Experimental Design: We performed a pooled analysis of five phase II studies that included patients with TNBC treated with neoadjuvant platinum-based chemotherapy to evaluate the association of TILs with HRD status (Myriad Genetics) and tumor mutation status. Furthermore, the relationship between pathologic response assessed using the residual cancer burden (RCB) index and HRD status with adjustment for TILs was evaluated.

Results: Among 161 patients, stromal TIL (sTIL) density was not significantly associated with HRD status ( = 0.107) or tumor mutation status ( = 0.391). In multivariate analyses, sTIL density [OR, 1.23; 95% confidence interval (CI), 0.94-1.61; = 0.139] was not associated with pCR, but was associated with RCB 0/I status (OR 1.62; 95% CI, 1.20-2.28; = 0.001). HRD was significantly associated with both pCR (OR 12.09; 95% CI, 4.11-44.29; = 7.82 × 10) and RCB 0/I (OR 10.22; 95% CI, 4.11-28.75; = 1.09 × 10) in these models.

Conclusions: In patients with TNBC treated with neoadjuvant platinum-based therapy, TIL density was not significantly associated with either tumor mutation status or HRD status. In this pooled analysis, HRD and sTIL density were independently associated with treatment response, with HRD status being the strongest predictor.