Clinical cancer research : an official journal of the American Association for Cancer Research, 4 1 2025 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
To assess prognosis of ER-low expression and its dynamics in HER2- metastatic breast cancer (BC) and to compare sensitivity to nivolumab between ER-low and triple-negative (TN) BC.
Experimental design
Two cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic BC, and one prospective cohort of 110 patients with ER<10%/HER2- metastatic BC enrolled in the TONIC trial (testing nivolumab). Endpoints were: overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort; progression-free survival (PFS), OS, and clinical benefit rate (CBR) in the TONIC trial.
Results
ER-low BC were 7.3% of retrospective cases, 15/110 of the TONIC. In the retrospective cohort, patients with ER-low BC had significantly poorer OS (p<0.001) and numerically shorter PRS (p=0.230) compared to ER+/HER2- BC, and numerically longer OS (p=0.098) and significantly longer PRS (p=0.017) compared to TNBC. In the TONIC, patients with ER-low BC, compared to TN, showed similar response to nivolumab (CBR: 20.0% vs 22.1%, p=1), PFS (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- BC (n=565), the conversion towards ER-low or TNBC at metastasis conferred independent negative prognostic impact both for OS (p=0.002 and 0.001, respectively) and PRS (p=0.018 and p=0.001, respectively).
Discussion
We provided evidence of the prognostic role of ER-low expression and its dynamics in patients with HER2- metastatic BC. We offered insights into sensitivity to antiPD1 in metastatic BC, showing that patients with ER-low BC have comparable likelihood of responding to nivolumab as those with TNBC.
