Abstract | PURPOSE: PATIENTS AND METHODS: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. RESULTS: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. CONCLUSION: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.
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Authors | Harold J Burstein, Lyndsay N Harris, Rebecca Gelman, Susan C Lester, Raquel A Nunes, Carolyn M Kaelin, Leroy M Parker, Leif W Ellisen, Irene Kuter, Michele A Gadd, Roger L Christian, Patricia Rae Kennedy, Virginia F Borges, Craig A Bunnell, Jerry Younger, Barbara L Smith, Eric P Winer |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 21
Issue 1
Pg. 46-53
(Jan 01 2003)
ISSN: 0732-183X [Print] United States |
PMID | 12506169
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Doxorubicin
- Cyclophosphamide
- Receptor, ErbB-2
- Trastuzumab
- Paclitaxel
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Breast Neoplasms
(drug therapy, mortality, pathology, surgery)
- Combined Modality Therapy
- Cyclophosphamide
(therapeutic use)
- Disease-Free Survival
- Doxorubicin
(therapeutic use)
- Female
- Humans
- Middle Aged
- Paclitaxel
(therapeutic use)
- Pilot Projects
- Receptor, ErbB-2
- Trastuzumab
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