Abstract
This study aimed to investigate the clinicopathological characteristics, response to chemotherapy, and clinical outcomes according to estrogen receptor (ER) expression levels in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC). ER expression levels were categorized as ER-negative (expression in <1% of tumor cells), ER-low positive (1-10%), ER-intermediate positive (11-50%), and ER- high positive (>50%). Of the 1,365 cases, 647 (47.4%) were classified as ER-negative, 49 (3.6%) as ER- low positive, 48 (3.5%) as ER-intermediate positive, and 621 (45.5%) as ER-high positive BCs in pre-NAC biopsies. ER-intermediate positive tumors as well as ER-low positive tumors showed no differences in clinicopathological characteristics compared to ER-negative tumors with the exception of progesterone receptor positivity. While ER-low positive and ER-negative tumors showed similar chemo-responsiveness, ER-intermediate positive tumors were less responsive to NAC compared to ER-negative tumors. In patients with residual disease, pre- and post-NAC ER expression levels were found to be independent prognostic factors, but with no significant differences among ER-negative, ER-low positive, and ER-intermediate positive tumors. Our study indicates that ER-low positive BCs are similar to ER-negative BCs and that ER-intermediate positive BCs exhibit characteristics heterogeneous between ER-negative and ER-high positive BCs in terms of clinicopathological characteristics, chemo-responsiveness, and clinical outcomes.
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The datasets generated and/or analyzed during the current study are not publicly available due to privacy concerns and institutional policy, but are available from the corresponding author on reasonable request.
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Acknowledgements
This study was funded by National Research Foundation of Korea (NRF)’s Basic Science Research Program to Park SY by the Ministry of Science and ICT (Grant No. 2022R1F1A1065468). The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
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K.B. participated in the interpretation and analysis of data and drafted the manuscript. H.J.S. and Y.R.C. participated in the acquisition and interpretation of pathological data. H.C.S., E.K.K., K.J.S., S.H.K., and J.H.K. participated in the acquisition of clinical data. H.J.K. and S.Y.P. conceived of the study, participated in its design and interpretation, and were responsible for the preparation of the manuscript. All authors read and approved of the final paper.
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Bai, K., Sung, HJ., Chung, Y.R. et al. Impact of estrogen receptor expression levels on chemo-responsiveness and prognosis of breast cancer patients treated with neoadjuvant chemotherapy. npj Breast Cancer (2026). https://doi.org/10.1038/s41523-026-00907-2
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DOI: https://doi.org/10.1038/s41523-026-00907-2
