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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

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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.

Clinical trial registration

NCT01613560.

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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.

Abbreviations

ALND:

Axillary lymph node dissection

BCS:

Breast-conserving surgery

DDFS:

Distant disease-free survival

ER:

Estrogen receptor

FISH:

Fluorescence in situ hybridization

HER2:

Human Epidermal Growth Factor Receptor 2

NACT:

Neoadjuvant chemotherapy

NET:

Neoadjuvant endocrine therapy

pCR:

Pathological complete response

PEPI:

Preoperative Endocrine Prognostic Index

RFS:

Recurrence-free survival

SLNB:

Sentinel lymph node biopsy

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Funding

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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Author notes

  1. Xinguang Wang, Zhaoqing Fan and Xing Wang have contributed equally to this work.

Authors and Affiliations

  1. Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Xinguang Wang, Zhaoqing Fan, Xing Wang, Yingjian He, Tianfeng Wang, Yuntao Xie, Jinfeng Li & Tao Ouyang

  2. Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China

    Yiqiang Liu

  3. Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Xiang Wang & Bailin Zhang

  4. Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China

    Zefei Jiang & Tao Wang

  5. Department of Breast Surgery, Cheeloo College of Medicine, The Second Hospital, Shandong University, Shandong, China

    Zhigang Yu & Fei Wang

  6. Breast Disease Center, Peking University First Hospital, Beijing, China

    Yinhua Liu

  7. Department of Breast Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

    Yanping Li

  8. Department of Breast Surgery, The Second Hospital of Harbin Medical University, Heilongjiang, China

    Jianguo Zhang

  9. Department of General Surgery, Clinical School of Medicine, Tsinghua Changgung Hospital, Tsinghua University, Beijing, China

    Bin Luo

  10. Department of Breast Surgery, Beijing Chao Yang Hospital, Capital Medical University, Beijing, China

    Hongchuan Jiang

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  1. Xinguang Wang
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  2. Zhaoqing Fan
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  3. Xing Wang
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  9. Tao Wang
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  10. Zhigang Yu
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  20. Tao Ouyang
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Contributions

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.

Corresponding author

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). https://doi.org/10.1007/s10549-022-06686-1

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