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

Autor:	Telli ML; Stanford University School of Medicine, Stanford, California. mtelli@stanford.edu., Chu C; Stanford University School of Medicine, Stanford, California., Badve SS; Indiana University, Indianapolis, Indiana., Vinayak S; University of Washington School of Medicine, Seattle, Washington., Silver DP; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Isakoff SJ; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Kaklamani V; University of Texas Health Science Center, San Antonio, Texas., Gradishar W; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois., Stearns V; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland., Connolly RM; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland., Ford JM; Stanford University School of Medicine, Stanford, California., Gruber JJ; Stanford University School of Medicine, Stanford, California., Adams S; New York University Perlmutter Cancer Center, New York, New York., Garber J; Harvard Medical School, Boston, Massachusetts.; Dana Farber Cancer Institute, Boston, Massachusetts., Tung N; Beth Israel Deaconess Medical Center, Boston, Massachusetts., Neff C; Myriad Genetics, Inc., Salt Lake City, Utah., Bernhisel R; Myriad Genetics, Inc., Salt Lake City, Utah., Timms KM; Myriad Genetics, Inc., Salt Lake City, Utah., Richardson AL; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jun 01; Vol. 26 (11), pp. 2704-2710. Date of Electronic Publication: 2019 Dec 03.
DOI:	10.1158/1078-0432.CCR-19-0664
Abstrakt:	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. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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