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HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer

  • Epidemiology
  • Published:
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Abstract

Purpose

Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC.

Methods

Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0.

Results

In total, 855 HER2-negative patients were identified. The median follow-up was 59 months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0.

Conclusion

Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil

    Luciana de Moura Leite, Marcelle Goldner Cesca, Monique Celeste Tavares, Debora Maciel Santana, Erick Figueiredo Saldanha, Paula Tavares Guimarães, Daniella Dias Silva Sá, Maria Fernanda Evangelista Simões, Rafael Lima Viana, Francisca Giselle Rocha, Simone Klog Loose, Sinara Figueiredo Silva, Rafaela Pirolli, Camilla Albina Zanco Fogassa, Bruna Raphaeli Silva Mattos, Fernando Augusto Batista Campos, Solange Moraes Sanches, Vladmir Cláudio Cordeiro de Lima & Noam Falbel Pondé

Authors
  1. Luciana de Moura Leite
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  2. Marcelle Goldner Cesca
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  3. Monique Celeste Tavares
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  14. Camilla Albina Zanco Fogassa
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Contributions

All authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and agreed to its submission. Study concepts: Luciana de Moura Leite, Marcelle Goldner Cesca, Solange Moraes Sanches, Vladmir Cláudio Cordeiro de Lima, and Noam Falbel Pondé. Study design: Luciana de Moura Leite, Marcelle Goldner Cesca, and Noam Falbel Pondé. Data acquisition: Luciana de Moura Leite, Marcelle Goldner Cesca, Monique Celeste Tavares, Debora Maciel Santana, Erick Figueiredo Saldanha, Paula Tavares Guimarães, Daniela Dias Silva Sá, Maria Fernanda Evangelista Simões, Rafael Lima Viana, Francisca Giselle Rocha, Simone Klog Loose, Sinara Figueiredo Silva, Rafaela Pirolli, Camilla Albina Zanco Fogassa, Bruna Raphaeli Silva Mattos, and Fernando Augusto Batista Campos. Quality control of data and algorithms: Luciana de Moura Leite, Vladmir Cláudio Cordeiro de Lima, and Noam Falbel Pondé. Data analysis and interpretation: Luciana de Moura Leite, Vladmir Cláudio Cordeiro de Lima, and Noam Falbel Pondé. Statistical analysis: Luciana de Moura Leite.

Corresponding author

Correspondence to Luciana de Moura Leite.

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Conflicts of interest

The authors have no known competing financial interests or personal relationships that have influenced the work reported in the manuscript. Luciana de Moura Leite, Monique Celeste Tavares, Debora Maciel Santana, Erick Figueiredo Saldanha, Paula Tavares Guimarães, Daniela Dias Silva Sá, Maria Fernanda Evangelista Simões, Rafael Lima Viana, Francisca Giselle Rocha, Simone Klog Loose, Sinara Figueiredo Silva, Rafaela Pirolli, Camilla Albina Zanco Fogassa and Bruna Raphaeli Silva Mattos, Fernando Augusto Batista Campos, Solange Moraes Sanches, Vladmir Cláudio Cordeiro de Lima, and Noam Falbel Pondé report no conflict of interest. Marcelle Goldner Cesca reports have received travel grants from Daiishi Sankyo.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of AC Camargo Cancer Center (registration number CAAE: 21308019.9.0000.5432).

Consent to participate

Given the retrospective nature of the study and that all the procedures being performed were part of the routine care, individual informed consent to participate was waived by the local Ethics Committee of AC Camargo Cancer Center.

Consent for publication

Given the retrospective nature of the study and that all the procedures being performed were part of the routine care, individual informed consent for publication was waived by the local Ethics Committee of AC Camargo Cancer Center. A partial analysis of this study has been presented as a Poster at 2020 San Antonio Breast Cancer Symposium (DOI: 10.1158/1538-7445.SABCS20-PS4- 40).

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de Moura Leite, L., Cesca, M.G., Tavares, M.C. et al. HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer. Breast Cancer Res Treat 190, 155–163 (2021). https://doi.org/10.1007/s10549-021-06365-7

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