Patients who have HER2-negative breast cancer and low estrogen receptor (ER) expression have clinical characteristics and outcomes similar to those of patients with triple-negative breast cancer (TNBC), according to research published in npj Breast Cancer.

Based on this finding, researchers recommended that patients with HER2-negative, ER-low breast cancer be included in trials of patients with TNBC.

This study included 516 participants with stage I-III HER2-negative breast cancer and ER/progesterone receptor (PR) expression less than 10%. The 451 patients with TNBC represented 87.4% of the participants, while 65 patients with low-ER breast cancer represented 12.6%. Clinico-pathologic characteristics and median age at diagnosis, as well as chemotherapy use patterns, were similar across the 2 groups.

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The researchers found no difference in recurrence-free survival or overall survival between the 2 groups. The rates of pathologic complete response with contemporary neoadjuvant chemotherapy regimens were also similar in both groups, which is consistent with earlier results.

The researchers noted that breast cancer patients in the low ER/PR-expression group are a relatively small subset of those with early-stage HER2-negative disease, but they have similar clinical behavior, chemosensitivity, and survival outcomes as patients with TNBC.

“Our study findings add further evidence for the need for systematic evaluation of this subgroup with respect to effectiveness of novel TNBC-specific therapies and degree of potential benefit from endocrine therapy,” the researchers wrote. “These findings also bring to the forefront the potential need to reevaluate the ER/PR cutoff for clinical trials in TNBC. If the low-ER group is indeed similar to TNBC, then the current approach of adhering to the 1% cutoff may lead to denying this group access to effective TNBC therapy just to ensure that some marginal endocrine therapy benefit is not lost. Findings from the current study support consideration for inclusion of patients with low-ER HER2-negative disease in future TNBC clinical trials.”

This study was limited by a relatively small number of patients in the low-ER group and a lack of central testing for ER/PR.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Yoder R, Kimler BF, Staley JM, et al. Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancerNPJ Breast Cancer. 2022;8(1):80. doi:

This article originally appeared on Oncology Nurse Advisor