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Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer

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Abstract

The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the ErbB receptors or downstream effectors may repress ER expression. Here the authors investigated whether gefitinib, given neoadjuvant in combination with epirubicin and cyclophosphamide (EC), could restore ER expression. Eligible patients in the NICE trial were women with unilateral, primary operable, ER negative invasive breast cancer ≥2 cm. Material from patients randomized and completing treatment (four cycles of neoadjuvant EC plus 12 weeks of either gefitinib or placebo) in the NICE trial having available ER status both at baseline and after neoadjuvant treatment were eligible for this study. Tumors with indication of changed ER phenotype (based on collected pathology reports) were immunohistochemically reassessed centrally. 115 patients were eligible for this study; 59 patients in the gefitinib group and 56 patients in the placebo group. Five (4.3%) of 115 tumors changed ER phenotype from negative to positive. A change was seen in three patients in the gefitinib (5.1%) and in two patients in the placebo (3.6%) group with a difference of 1.51% (95% CI, −6.1–9.1). Results of the NICE trial have been reported previously. Post-operative reassessment of ER expression changed the assessment of ER status in a small but significant fraction of patients and should, whenever possible, be performed following neoadjuvant chemotherapy for ER negative breast cancer. Gefitinib did not affect the reversion rate of ER negative tumors.

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Acknowledgments

The NICE trial and this study was sponsered by Astra Zeneca. The authors would like to thank the following centers for collaboration: Sweden: Malmö Hospital and Lund University Hospital. Norway: Trondheim Hospital and Rikshospitalet-Radiumhospitalet Oslo. Denmark: Herlev Hospital, Aarhus University Hospital, Odense University Hospital, Vejle Hospital, Roskilde Hospital, Naestved Hospital and Ringsted Hospital.

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Authors and Affiliations

  1. Department of Oncology, 5073, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Mogens Bernsdorf, Hans von der Maase & Bent Ejlertsen

  2. Department of Pathology, Herlev University Hospital, Herlev, Denmark

    Eva Balslev

  3. Department of Breast Cancer Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark

    Anne E. Lykkesfeldt

  4. Department of Breast Surgery, Copenhagen University Hospital, Copenhagen, Denmark

    Niels Kroman

  5. Department of Oncology, Hillerød Hospital, Copenhagen, Denmark

    Eva Harder

  6. Department of Oncology, Lillebaelt Hospital, Vejle, Denmark

    Erik H. Jakobsen

  7. Department of Pathology, Clinical Sciences, Lund University Hospital, Lund, Sweden

    Dorthe Grabau

  8. Danish Breast Cancer Cooperative Group, Copenhagen, Denmark

    Bent Ejlertsen

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  1. Mogens Bernsdorf
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  2. Eva Balslev
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  3. Anne E. Lykkesfeldt
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  4. Niels Kroman
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  5. Eva Harder
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  7. Erik H. Jakobsen
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  9. Bent Ejlertsen
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Correspondence to Mogens Bernsdorf.

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Bernsdorf, M., Balslev, E., Lykkesfeldt, A.E. et al. Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer. Breast Cancer Res Treat 128, 165–170 (2011). https://doi.org/10.1007/s10549-011-1535-x

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  • DOI: https://doi.org/10.1007/s10549-011-1535-x

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