TY - JOUR
T1 - Association of Tumor-Infiltrating Lymphocytes with Homologous Recombination Deficiency and BRCA1/2 Status in Patients with Early Triple-Negative Breast Cancer
T2 - A Pooled Analysis
AU - Telli, Melinda L.
AU - Chu, Charles
AU - Badve, Sunil S.
AU - Vinayak, Shaveta
AU - Silver, Daniel P.
AU - Isakoff, Steven J.
AU - Kaklamani, Virginia
AU - Gradishar, William
AU - Stearns, Vered
AU - Connolly, Roisin M.
AU - Ford, James M.
AU - Gruber, Joshua J.
AU - Adams, Sylvia
AU - Garber, Judy
AU - Tung, Nadine
AU - Neff, Chris
AU - Bernhisel, Ryan
AU - Timms, Kirsten M.
AU - Richardson, Andrea L.
N1 - Funding Information:
Myriad Genetics performed HRD testing on a research basis for this analysis. Research reported in this article was supported by Susan G Komen for the Cure (grant 150062 to M.L. Telli), Breast Cancer Research Foundation (BCRF-18-137 to A.L. Richardson), National Center For Advancing Translational Sciences of the NIH under Award Number UL1TR003142 (to M.L. Telli and J.M. Ford), Stanford Cancer Institute (to M.L. Telli and J.M. Ford), and the Translational Breast Cancer Research Consortium (to V. Stearns and R.M. Connolly).
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-19-0664
DO - 10.1158/1078-0432.CCR-19-0664
M3 - Article
C2 - 31796517
AN - SCOPUS:85085904563
SN - 1078-0432
VL - 26
SP - 2704
EP - 2710
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -