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Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: results from the randomized Phase II NeoMET trial

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Abstract

Purpose

Breast cancer patients with metabolic syndrome (MetS) and its components show worse treatment responses to chemotherapy. Metformin is a widely used antidiabetic drug which also shows potential anticancer effect. This study aims to evaluate the efficacy, safety, and metabolic parameters change of metformin combined with docetaxel, epirubicin, and cyclophosphamide (TEC) in neoadjuvant treatment (NAT) for breast cancer patients with metabolic abnormality.

Methods

Eligible breast cancer patients were randomized to receive six cycles of TEC (docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2, d1, q3w) or TEC with metformin (TECM, TEC with oral metformin 850 mg once daily for the first cycle, then 850 mg twice daily for the following cycles). The primary end point was total pathological complete response (tpCR, ypTis/0N0) rate.

Results

Ninety-two patients were enrolled and randomized from October 2013 to December 2019: 88 patients were available for response and safety assessment. The tpCR rates were 12.5% (5/40) and 14.6% (7/48) in the TEC and TECM groups, respectively (P = 0.777). There was no difference in Ki67 decrease after NAT between two groups (P = 0.456). Toxicity profile were similar between two groups. No grade 3 or higher diarrhea were recorded. Total cholesterol (TC) and high-density lipoprotein cholesterol worsened after NAT in the TEC arm but remained stable in the TECM arm. The absolute increase of TC and low-density lipoprotein cholesterol (LDL-C) was significantly lower in the TECM group compared with the TEC group. After a median follow-up of 40.8 (4.7–70.8) months, no survival difference was observed between TEC and TECM groups (all P > 0.05).

Conclusion

Adding metformin to TEC didn’t increase pCR rate and disease outcome in breast cancer patients with metabolic abnormality. However, additional metformin treatment with chemotherapy would prevent TC and LDL-C increase after NAT.

Trial Registration ClinicalTrials.gov Identifier: NCT01929811.

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Data availability

The datasets analyzed in the present study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors are grateful to the patients, their families, and caregivers for participating in NeoMET trial. The authors also thank the study investigators and site staff for their participation.

Funding

This study was funded by the National Natural Science Foundation of China (82072937, 82072897); Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20172007); Shanghai Jiao Tong University Yi Gong Jiao Cha Funding (YG2019QNA30); and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine- “Guangci Excellent Youth Training Program” (GCQN-2019-B07). All these financial sponsors had no role in the study design, data collection, analysis, or interpretation.

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Author notes

  1. Jiahui Huang and Yiwei Tong contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China

    Jiahui Huang, Yiwei Tong, Jin Hong, Ou Huang, Jiayi Wu, Jianrong He, Weiguo Chen, Yafen Li, Xiaosong Chen & Kunwei Shen

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  1. Jiahui Huang
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Correspondence to Xiaosong Chen or Kunwei Shen.

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Ethical approval

The present study was reviewed and approved by independent ethical committees of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (2013-32a/2013–7-31). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Huang, J., Tong, Y., Hong, J. et al. Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: results from the randomized Phase II NeoMET trial. Breast Cancer Res Treat 197, 525–533 (2023). https://doi.org/10.1007/s10549-022-06821-y

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