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HER2 status in hormone receptor positive premenopausal primary breast cancer adds prognostic, but not tamoxifen treatment predictive, information

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Abstract

Background

Overexpression of human epidermal growth factor receptor 2 (HER2) or amplification of its gene is a prognostic factor in primary breast cancer and a predictor for tamoxifen treatment efficacy in oestrogen receptor (ER) positive disease. In the present study we explored a defined cohort of breast cancer patients included in a randomised trial in order to assess prognostic and tamoxifen treatment information yielded by HER2 status.

Methods

Premenopausal breast cancer patients with stage II tumours (n = 564) were included and allocated to 2 years of adjuvant tamoxifen treatment versus no adjuvant treatment. ER, progesterone receptor (PR) status and HER2 status was determined by immunohistochemistry using a tissue microarray. HER2 amplification was analysed by fluorescent in situ hybridisation and tumours being amplified and/or HER2 3+ were considered HER2+. HER2 status was evaluable in 83% of the patients and 12.6% were HER2+. In untreated patients, HER2 was a negative prognostic factor in ER+ patients, HR 2.95; 95% CI: 1.61–5.38, p < 0.001, but not in ER- patients, HR 0.67; 95% CI: 0.28–1.61, p = 0.4, and a significant interaction between the two markers was found, p < 0.01. HER2 status was not related to tamoxifen treatment efficacy in ER+ patients (term of interaction p = 0.95). When stratifying for PR status, similar results were achieved.

Discussion

HER2+ and ER+ breast cancer constituted a subgroup of tumours with poor prognosis in premenopausal breast cancer, whereas no treatment interaction was found between HER2 status and tamoxifen in ER+ tumours. The poor prognosis in HER2+ and ER+ patients may interfere with the interpretation of HER2 data in non-randomised trials of adjuvant tamoxifen.

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Acknowledgement

The study was supported by funds from the Swedish Cancer Society, Swedish Research Council, Gunnar Nilsson Cancer Foundation, Mrs Berta Kamprad Foundation, Skane county council’s research and development Foundation and Minna Breining Cancer Foundation at the Department of Oncology, Lund.

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Authors and Affiliations

  1. Department of Surgery, Institution of Clinical Sciences, Lund University, Lund, 221 85, Sweden

    Lisa Rydén

  2. Division of Pathology, Institution of Laboratory Medicine, Malmö University Hospital, Malmo, Sweden

    Göran Landberg

  3. Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linköping University, Linkoping, Sweden

    Olle Stål & Bo Nordenskjöld

  4. Department of Oncology, Institution of Clinical Sciences, Lund University, Lund, Sweden

    Mårten Fernö & Pär-Ola Bendahl

Authors
  1. Lisa Rydén
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  2. Göran Landberg
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  3. Olle Stål
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  4. Bo Nordenskjöld
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  5. Mårten Fernö
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  6. Pär-Ola Bendahl
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Correspondence to Lisa Rydén.

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Rydén, L., Landberg, G., Stål, O. et al. HER2 status in hormone receptor positive premenopausal primary breast cancer adds prognostic, but not tamoxifen treatment predictive, information. Breast Cancer Res Treat 109, 351–357 (2008). https://doi.org/10.1007/s10549-007-9660-2

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  • DOI: https://doi.org/10.1007/s10549-007-9660-2

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