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Prognostic molecular markers and neoadjuvant therapy response in anthracycline-treated breast cancer patients

  • Gynecologic Oncology
  • Published:
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Abstract

Background

Identifying biomarkers that can predict the prognosis and treatment response is helpful for individualizing breast cancer (BC) therapy. A neoadjuvant treatment setting is ideal for testing biomarkers capable of predicting the treatment response. This study analyzed the value of immunohistochemical biomarkers for predicting pathological complete response (pCR) and prognosis in a group of BC patients receiving standardized treatment.

Patients and methods

A total of 100 BC patients were treated with neoadjuvant chemotherapy (four cycles of epirubicin and cyclophosphamide) between 2000 and 2005. Formalin-fixed and paraffin-embedded core biopsies were taken before chemotherapy for immunohistochemical staining of ER, PgR, HER2, Bcl-2, p53, cyclin D1, CK5/6, CK8, CK18, and TOP2A. Patient and tumor characteristics and biomarker scores were used to predict pCR and prognosis, using logistic regression and Cox proportional hazard models.

Results

pCR was achieved in 11 patients and was predicted by the established marker Ki-67. In addition, CK5/6 and CK18 improved the prediction model and were associated with lower pCR rates. For the prognosis, only the established markers nodal status, Ki-67, and PgR predicted overall survival and nodal status; Ki-67 and PgR predicted distant disease-free survival.

Conclusions

In this small retrospective study, CK5/6 and CK18 appeared to improve prediction of pCR in addition to the established markers. CK5/6 may indicate a tumor type resembling a basal phenotype that is more resistant to anthracycline-based therapy, and CK18 may indicate a luminal subtype that is more resistant to chemotherapy. However, these results need to be replicated in larger studies.

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Conflict of interest

The authors hereby declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

    David L. Wachter & Arndt Hartmann

  2. Department of Gynecology and Obstetrics, Erlangen–Nuremberg Comprehensive Cancer Center, University Breast Center of Franconia, Erlangen University Hospital, Friedrich Alexander University of Erlangen–Nuremberg, Universitaetsstrasse 21–23, 91054, Erlangen, Germany

    Peter A. Fasching, Lothar Haeberle, Stefan P. Renner, Michael P. Lux, Matthias W. Beckmann, Claudia Rauh & Michael G. Schrauder

  3. Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Peter A. Fasching

  4. Institute of Diagnostic Radiology, Erlangen University Hospital, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany

    Ruediger Schulz-Wendtland

  5. Institute of Pathology, St. Vincentius Hospitals, Karlsruhe, Germany

    Arno Dimmler

  6. Institute of Pathology, RegioMed Hospitals Ltd., Coburg, Germany

    Thomas Koscheck

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  1. David L. Wachter
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  2. Peter A. Fasching
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  3. Lothar Haeberle
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  7. Stefan P. Renner
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  8. Michael P. Lux
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  11. Claudia Rauh
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  12. Michael G. Schrauder
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Corresponding author

Correspondence to Peter A. Fasching.

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Wachter, D.L., Fasching, P.A., Haeberle, L. et al. Prognostic molecular markers and neoadjuvant therapy response in anthracycline-treated breast cancer patients. Arch Gynecol Obstet 287, 337–344 (2013). https://doi.org/10.1007/s00404-012-2534-9

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  • DOI: https://doi.org/10.1007/s00404-012-2534-9

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