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Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study



For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI).


We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0–1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0–1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician.


A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4–104 months), patients who had PEPI 0–1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5–99.9%) for PEPI 0–1 or pCR group vs. 93.7% (95% CI 89.6–97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases.


PEPI 0–1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted.

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Fig. 1
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Data availability

Datasets generated during and/or analyzed in this study can be made available upon reasonable request. Please contact the corresponding author for more information.



Axillary lymph node dissection


Breast-conserving surgery


Distant disease-free survival


Estrogen receptor


Fluorescence in situ hybridization


Human Epidermal Growth Factor Receptor 2


Neoadjuvant chemotherapy


Neoadjuvant endocrine therapy


Pathological complete response


Preoperative Endocrine Prognostic Index


Recurrence-free survival


Sentinel lymph node biopsy


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This study was supported by Novartis. The funder was not involved in the collection, analysis, or interpretation of the data, nor in the decision to submit for publication. The corresponding author confirms that he had access to all data and had final responsibility for the decision to submit for publication.

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Authors and Affiliations



WXG, FZQ, WX, HYJ, LYQ, and OYT were involved in the study design, data collection and analysis, interpretation of results, manuscript writing, and decision to submit. ZBL, WT, WF, WTF, XYT, and LJF were involved in the data collection and analysis, manuscript writing, and decision to submit. WX, JZF, YZG, LYH, LYP, ZJG, LB, and JHC were involved in the study design, manuscript writing, and decision to submit.

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Correspondence to Tao Ouyang.

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The authors declare no competing interest.

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The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines and was approved by the institutional review board of all participating centers. All patients gave written informed consent.

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Wang, X., Fan, Z., Wang, X. et al. Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study. Breast Cancer Res Treat 195, 301–310 (2022).

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  • Neoadjuvant endocrine therapy
  • Breast cancer
  • Pathological response
  • Survival