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Weekly paclitaxel plus carboplatin with or without trastuzumab as neoadjuvant chemotherapy for HER2-positive breast cancer: loss of HER2 amplification and its impact on response and prognosis

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Abstract

Purpose

Neoadjuvant chemotherapy (NCT) plus anti-HER2 agents are the standard of care for locally advanced HER2-positive breast cancer. The aim of this study was to evaluate the prevalence and prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without trastuzumab.

Methods

549 consecutive HER2-positive patients were included in this study. 379 patients were treated with paclitaxel, carboplatin, and trastuzumab (PCH cohort) and 170 were treated with paclitaxel and carboplatin only (PC cohort). Conversion of biomarkers before and after NCT was evaluated via immunohistochemistry (IHC) test. Cox regression model was used to investigate prognostic markers to relapse-free survival (RFS).

Results

50.9% patients were considered as pCR responder in PCH cohort, whereas only 25.9% of patients experienced pCR in PC cohort (P < 0.001). HER2 loss were more frequently shown in PCH cohort with a proportion of 19.8%, compared to 9.4% in PC cohort (P = 0.009). In PCH cohort, patients with a loss of HER2 expression tended to have a higher risk of relapse compared to patients with maintained HER2 expression (HR = 2.639, 95% CI 1.103–6.311, P = 0.029). However, it did not correlate to patient outcome in the PC cohort (P = 0.296). Loss of HER2 was also correlated to ER conversion in PCH cohort.

Conclusion

Our study has provided new evidence that anti-HER2 treatment has a significant impact on HER2 loss. Far more importantly, the loss of HER2 amplification could identify non-pCR patients with high risk of disease relapse, which might help in tailoring following systemic treatment.

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Acknowledgements

This research is supported by the National Natural Science Foundation of China (81302298). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, 399 Ling-Ling Road, Shanghai, 200032, People’s Republic of China

      Ruo-Xi Wang, Sheng Chen, Xi Jin, Can-Ming Chen & Zhi-Ming Shao

    2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

      Ruo-Xi Wang, Sheng Chen, Xi Jin, Can-Ming Chen & Zhi-Ming Shao

    3. Institutes of Biomedical Science, Fudan University, Shanghai, People’s Republic of China

      Zhi-Ming Shao

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    1. Ruo-Xi Wang
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    Correspondence to Sheng Chen or Zhi-Ming Shao.

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    Ruo-Xi Wang and Sheng Chen have contributed equally to this work.

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    Wang, RX., Chen, S., Jin, X. et al. Weekly paclitaxel plus carboplatin with or without trastuzumab as neoadjuvant chemotherapy for HER2-positive breast cancer: loss of HER2 amplification and its impact on response and prognosis. Breast Cancer Res Treat 161, 259–267 (2017). https://doi.org/10.1007/s10549-016-4064-9

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