Influence of neoadjuvant chemotherapy on HER2/neu status in invasive breast cancer

Clin Breast Cancer. 2013 Feb;13(1):53-60. doi: 10.1016/j.clbc.2012.09.011. Epub 2012 Oct 26.

Abstract

Introduction: Reliably estimating HER2/neu expression in breast cancer is important for predicting patient prognosis and optimizing adjuvant therapeutic strategies. In this retrospective cohort study, effects of NAC on HER2/neu status in invasive breast cancer were evaluated, and the related factors were analyzed.

Patients and methods: One hundred thirty-one patients with primary breast cancer were treated with anthracycline- and/or taxane-based NAC. HER2/neu status was evaluated by IHC on core needle biopsies of primary tumors before NAC and surgical resection specimens of post-NAC residual breast cancers or tumor-positive axillary lymph nodes. Thirty-two pairs of specimens with discordant HER2/neu IHC scores were analyzed by fluorescence in situ hybridization (FISH).

Results: A significant difference in HER2/neu status by IHC between core needle biopsies and surgical resection specimens in patients receiving NAC was observed. After NAC, 23.4% (29 of 124) of tumors showed downregulated HER2/neu expression by IHC. Alterations of HER2/neu IHC scores did not significantly correlate with tumor subtype, pathologic response to NAC, adjuvant regimen, or time interval from the last chemotherapy to surgery. HER2/neu protein overexpression level was associated with favorable pathologic response to anthracycline and taxane-based chemotherapy. However, tumors with altered HER2/neu IHC scores after NAC revealed stable HER2/neu gene amplification/nonamplification by FISH analysis.

Conclusion: Neoadjuvant chemotherapy for breast carcinoma resulted in the HER2/neu status alteration by IHC, but they have stable gene amplification status by FISH. HER2/neu protein overexpression indicated greater sensitivity to neoadjuvant anthracycline- and taxane-based chemotherapy. Thus, retesting HER2/neu IHC status in residual tumors after NAC should be considered in order to optimize adjuvant systemic therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / drug therapy
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies

Substances

  • Receptor, ErbB-2