Circulating extracellular domain of HER2 can be correlated with clinical response to chemotherapy in locally advanced breast cancer

V. Stearns, H. Yamauchi, B. Singh, R. Slack, D. F. Hayes

Research output: Contribution to journalArticle

Abstract

Introduction: We previously reported results of a pilot clinical trial correlating surrogate endpoint biomarkers at baseline, during, and following neoadjuvant chemotherapy for locally advanced breast cancer with clinical and pathological response rates (pASCO 2000). Overexpression of the HER2 receptor appears to be predictive of response to specific therapies in breast cancer. However, only a few studies assessed circulating extracellular domain of HER2 (ECD/ HER2) with response to neoadjuvant therapies, and none had measurements with each cycle of therapy. Patients and Methods: Women with a histologically confirmed T3 or T4. infiltrating carcinoma of the breast received 3 cycles of doxorubicn (A) 90 mg/ m2 followed by 3 cycles of paclitaxel (T) 250 mg/m2, or the reverse sequence (AT or TA), given 14 days apart with filgastrim. Nine additional women received 4 cycles of A 60mg/m2 followed by 4 cycles of T 175 mg/m2, or the reverse, 14 days apart with filgastrim. We measured baseline status of tissue HER2 (immunohistochemistry, CB11, Immunotech, Wesbrook, ME), and baseline and serial levels of circulating ECD/HER2 (Human HER-2/neu Quantitative ELISA, Oncogene Science). Results: Twenty-nine women were included in the analysis. Median number of samples per patient was 5 (1-8). At baseline, 4/29 (14%) of all patients and 4/ 9 (44%) of those with HER2 positive breast cancers by IHC (2+ or 3+ by DAKO system) had elevated circulating ECD/HER2 levels (greater than 15 ng/ml). All 4 of the patients with elevated pre-treatment levels had excellent clinical response to the regimen and marker levels that declined to normal following a median of 2 cycles of chemotherapy (1-3). Two of those women had stage IIIA disease and suffered disease recurrence (12 and 17 months after the definitive surgical procedure). Two additional women had limited stage IV disease and developed disease progression while on tamoxifen (5 and 7 months after completing the chemotherapy and local therapy). Conclusions: High baseline levels of ECD/HER2 correlate with tissue HER2 status, and decreasing levels correspond to clinical response to the chemotherapy. Further studies are required to correlate ECD/HER2 elevations with long term outcomes.

Original languageEnglish (US)
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - Dec 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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