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: | Joshua J. Gruber, Kirsten Timms, Nadine Tung, Vered Stearns, Daniel P. Silver, Andrea L. Richardson, Ryan Bernhisel, Judy Garber, Shaveta Vinayak, James M. Ford, Melinda L. Telli, Virginia G. Kaklamani, Chris Neff, Steven J. Isakoff, Sunil Badve, William J. Gradishar, Sylvia Adams, Roisin M. Connolly, Charles Chu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Mutation Chemotherapy Stromal cell Multivariate analysis Tumor-infiltrating lymphocytes business.industry medicine.medical_treatment medicine.disease medicine.disease_cause 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Breast cancer 030220 oncology & carcinogenesis Internal medicine medicine Stage (cooking) business Triple-negative breast cancer |
| Zdroj: | Clinical Cancer Research. 26:2704-2710 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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