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

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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 11 Pg. 2704-2710 (06 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 31796517 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Biomarkers, Tumor

Topics

• Adult
• Aged
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Biomarkers, Tumor (genetics)
• Clinical Trials, Phase II as Topic
• Female
• Follow-Up Studies
• Homologous Recombination
• Humans
• Lymphocytes, Tumor-Infiltrating (immunology)
• Meta-Analysis as Topic
• Middle Aged
• Multicenter Studies as Topic
• Mutation
• Prognosis
• Prospective Studies
• Survival Rate
• Triple Negative Breast Neoplasms (genetics, immunology, pathology, surgery)
• Young Adult