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Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer

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Abstract

Purpose

In stage IV breast cancer, the efficacy of human epidermal growth factor receptor 2 (HER2) targeted therapies in cases with discordance in HER2 expression between primary and metastatic site is not well known. We studied progression free (PFS) and overall survival (OS) by HER2 concordance when treating women with taxane–trastuzumab (± pertuzumab) in first or second line and trastuzumab-emtansine (T-DM1) or capecitabine–lapatinib in later lines.

Patients and methods

Retrospective monocentric study including all breast cancer patients receiving trastuzumab between January 2002 and September 2017 at the University Hospital in Leuven; we selected metastatic patients with an available HER2 status in primary and metastatic site. The Kaplan–Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model overall survival as a function group, correcting for possible confounders.

Results

We included 74 patients; 46 had an unchanged HER2 status (positive/positive), 9 lost HER2 (positive/negative), while 19 acquired HER2 amplification (negative/positive). 25 out of 28 cases with a discordant HER2 status were positive for ER and/or PgR in the primary site. HER2 positive/negative cases had a significantly lower PFS for taxane–trastuzumab–(pertuzumab) (PFS = 5.5 months), compared to HER2 positive/positive (PFS 9 months, p = 0.01) and HER2 negative/positive (PFS 14 months, p = 0.01) patients. PFS for later line T-DM1 (n = 30) was significantly higher for the HER2 positive/positive group (PFS 6.0 months) than for the discordant groups HER2 negative/positive (PFS 1.0 month, p = 0.04) and HER2 positive/negative (PFS 1.5 month, p = 0.01). After correcting for possible confounders, the HER2 positive/negative group had a significantly worse OS compared to HER2 positive/positive (HR 0.19, 95% CI 0.08–0.44) and negative/positive (HR 0.15, 95% 0.06–0.38).

Conclusion

Conversion of HER2 status was seen in 28 out of 74 cases and was mostly observed in hormone receptor-positive tumors. In contrast to patients with HER2 loss, patients with a positive conversion of HER2 status derived substantial benefit from first line treatment with taxane–trastuzumab–(pertuzumab). This study highlights the importance of re-biopsying the metastatic lesion and changing treatment according to the last HER2 result.

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Abbreviations

BC:

Breast cancer

PgR:

Progesterone receptor

CEP17:

Centromere enumerator probe 17

TTM:

Time to metastasis

NPI:

Nottingham Prognostic Index

ASCO/CAP:

American Society of Clinical Oncology/College of American Pathologist

ER:

Estrogen receptor

OS:

Overall survival

PFS:

Progression free survival

HER2:

Human epidermal growth factor receptor 2

CI:

Confidence intervals

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Elisa Van Raemdonck, P. Berteloot, I. Vergote & P. Neven

  2. Department of Biostatistics, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    A. Laenen

  3. Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    G. Floris

  4. Department of Pathology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    G. Floris

  5. Department of General Medical Oncology, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    H. Wildiers & K. Punie

Authors
  1. Elisa Van Raemdonck
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  2. G. Floris
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  6. H. Wildiers
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  7. K. Punie
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  8. P. Neven
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Corresponding authors

Correspondence to Elisa Van Raemdonck or P. Neven.

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The authors declare that they have no conflict of interest.

Ethical approval

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. For this type of retrospective study, formal consent is not required. The ethics committee of the University Hospitals Leuven approved the study.

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Van Raemdonck, E., Floris, G., Berteloot, P. et al. Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer. Breast Cancer Res Treat 185, 183–194 (2021). https://doi.org/10.1007/s10549-020-05935-5

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  • DOI: https://doi.org/10.1007/s10549-020-05935-5

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