Data from HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis
Year: 2023
Type: other
Abstract: Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1,079 triple-negative breast cancers (TNBC). Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n = 520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline combination Neo-ACT (n = 110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC cohort (n = 311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomization to ixabepilone (n = 68) or paclitaxel (n = 64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumors with integrated HAGE gene copy number changes, mRNA, and protein levels were analyzed. Results: In patients with EP-TNBC, who were chemotherapy-naïve, high HAGE protein expression (HAGE+) was associated with a higher risk of death [HR, 1.3; 95% confidence interval (CI), 1.2–1.5; P = 0.000005] when compared with HAGE− cases. Patients who received ACT and expressed mRNA-HAGE+ were at a lower risk of death than those who were mRNA–HAGE− (P = 0.004). The expression of HAGE was linked to the presence of tumor-infiltrating lymphocytes (TIL), and both features were found to be independent predictors for pathologic complete response (pCR, P < 0.001) and associated with prolonged survival (P < 0.01), following AC-Neo-ACT. In patients with residual disease, HAGE+ had a 2-fold death risk increase (P = 0.018) compared with HAGE−. Conclusions: HAGE expression is a potential prognostic marker and a predictor of response to anthracycline treatment in TNBC. A prospective clinical trial to examine the therapeutic value of HAGE for TNBC cases is warranted. Clin Cancer Res; 22(4); 905–14. ©2015 AACR.
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4361816670