Triple-negative breast cancer (TNBC) is, in part, defined by an immunohistochemical expression of less than 1% for estrogen receptor (ER)/progesterone receptor (PR) negativity. However, HER2-negative breast cancers with a slightly higher but still low ER expression of 1% to 10% have similar molecular features. And some suggest that patients with low-ER status might benefit from endocrine therapy, despite the currently limited data.

A group of researchers sought to compare the impact of these 2 types of breast cancer. Their findings were published in npj Breast Cancer.

The researchers analyzed the results of 516 participants with stage I-III HER2-negative breast cancer and ER/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%. They noted that 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 and overall survival between the 2 groups. The rates of pathologic complete response (pCR) with contemporary neoadjuvant chemotherapy regimens were also similar in both groups of patients, which is consistent with earlier results.

The researchers noted that breast cancer survivors 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. This called for researchers to focus more attention on this subset of patients and to delve into systematic evaluation that might generate more knowledge about the effectiveness of novel TNBC-specific therapies, as well as the potential benefit of endocrine therapies.

“These findings also bring to the forefront the potential need to reevaluate the ER/PR cutoff for clinical trials in TNBC,” they explained. “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.”

The study was limited by a relatively small number of patients, approximately 12.6% of the study participants, in the low-ER group and lack of central resting for ER/PR.

Disclosures: Some 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.