Association of Tumor-Infiltrating Lymphocytes with Homologous Recombination Deficiency and BRCA1/2 Status in Patients with Early Triple-Negative Breast Cancer: A Pooled Analysis

Melinda L. Telli, Charles Chu, Sunil S. Badve, Shaveta Vinayak, Daniel P. Silver, Steven J. Isakoff, Virginia Kaklamani, William Gradishar, Vered Stearns, Roisin M. Connolly, James M. Ford, Joshua J. Gruber, Sylvia Adams, Judy Garber, Nadine Tung, Chris Neff, Ryan Bernhisel, Kirsten M. Timms, Andrea L. Richardson

Research output: Contribution to journalArticle

Abstract

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, BRCA1/2 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 BRCA1/2 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 (P = 0.107) or tumor BRCA1/2 mutation status (P = 0.391). In multivariate analyses, sTIL density [OR, 1.23; 95% confidence interval (CI), 0.94-1.61; P = 0.139] was not associated with pCR, but was associated with RCB 0/I status (OR 1.62; 95% CI, 1.20-2.28; P = 0.001). HRD was significantly associated with both pCR (OR 12.09; 95% CI, 4.11-44.29; P = 7.82 × 10-7) and RCB 0/I (OR 10.22; 95% CI, 4.11-28.75; P = 1.09 × 10-7) in these models. CONCLUSIONS: In patients with TNBC treated with neoadjuvant platinum-based therapy, TIL density was not significantly associated with either tumor BRCA1/2 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.

Original languageEnglish (US)
Pages (from-to)2704-2710
Number of pages7
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Volume26
Issue number11
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Telli, M. L., Chu, C., Badve, S. S., Vinayak, S., Silver, D. P., Isakoff, S. J., Kaklamani, V., Gradishar, W., Stearns, V., Connolly, R. M., Ford, J. M., Gruber, J. J., Adams, S., Garber, J., Tung, N., Neff, C., Bernhisel, R., Timms, K. M., & Richardson, A. L. (2020). Association of Tumor-Infiltrating Lymphocytes with Homologous Recombination Deficiency and BRCA1/2 Status in Patients with Early Triple-Negative Breast Cancer: A Pooled Analysis. Clinical cancer research : an official journal of the American Association for Cancer Research, 26(11), 2704-2710. https://doi.org/10.1158/1078-0432.CCR-19-0664