Clinical cancer research : an official journal of the American Association for Cancer Research, Volume 31, Issue 24, 1 1 2025, Pages 5306-5316 Prognosis and Biological Characteristics of ER-Low Metastatic Breast Cancer: Results from a Multicenter Cohort and the TONIC Trial. Miglietta F, De Graaf M, Vernieri C, Piacentini F, Cacciatore M, Botticelli A, Vingiani A, Fotia G, Nicolè L, Griguolo G, Giarratano T, Massa D, Pellegrini V, Schiavi F, Porra F, Fassan M, Pruneri G, Dei Tos AP, Guarneri V, Kok M, Dieci MV
Purpose
The purpose of this study was to assess prognosis of estrogen receptor (ER)-low expression and its dynamics in HER2- metastatic breast cancer and to compare sensitivity to nivolumab between ER-low and triple-negative breast cancer (TNBC).
Experimental design
Two cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic breast cancer and one prospective cohort of 110 patients with ER <10%/HER2- metastatic breast cancer enrolled in the TONIC trial (testing nivolumab). Endpoints were overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort and progression-free survival, OS, and clinical benefit rate in the TONIC trial.
Results
A total of 7.3% of retrospective cases had ER-low breast cancer, 15 of 110 of the TONIC trial. In the retrospective cohort, patients with ER-low breast cancer had significantly poorer OS (P < 0.001) and numerically shorter PRS (P = 0.230) compared with ER+/HER2- breast cancer and numerically longer OS (P = 0.098) and significantly longer PRS (P = 0.017) compared with TNBC. In the TONIC trial, patients with ER-low breast cancer, compared with TNBC, showed similar response to nivolumab (clinical benefit rate: 20.0% vs. 22.1%; P = 1), progression-free survival (median, 1.7 vs. 2.0 months; P = 0.5), and OS (median, 5.3 vs. 8.6 months; P = 0.3). Among patients with primary ER+/HER2- breast cancer (n = 565), the conversion toward ER-low breast cancer or TNBC at metastasis conferred independent negative prognostic impact both for OS (P = 0.002 and P = 0.001, respectively) and PRS (P = 0.018 and P = 0.001, respectively).
Conclusions
We provided evidence of the prognostic role of ER-low expression and its dynamics in patients with HER2- metastatic breast cancer. We offered insights into sensitivity to anti-PD1 in metastatic breast cancer, showing that patients with ER-low breast cancer have comparable likelihood of responding to nivolumab as those with TNBC.
