HER2 and response to paclitaxel in node-positive breast cancer Journal Article
| Authors: | Hayes, D. F.; Thor, A. D.; Dressler, L. G.; Weaver, D.; Edgerton, S.; Cowan, D.; Broadwater, G.; Goldstein, L. J.; Martino, S.; Ingle, J. N.; Henderson, I. C.; Norton, L.; Winer, E. P.; Hudis, C. A.; Ellis, M. J.; Berry, D. A. |
| Article Title: | HER2 and response to paclitaxel in node-positive breast cancer |
| Abstract: | BACKGROUND: The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both. METHODS: We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed. RESULTS: No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P = 0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers. CONCLUSIONS: The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide. Copyright © 2007 Massachusetts Medical Society. |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; treatment outcome; treatment response; middle aged; major clinical study; clinical trial; cancer recurrence; doxorubicin; dose response; patient selection; paclitaxel; adjuvant therapy; chemotherapy, adjuvant; follow up; follow-up studies; antineoplastic agent; controlled clinical trial; multiple cycle treatment; breast cancer; gene amplification; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; antineoplastic agents, phytogenic; cyclophosphamide; breast neoplasms; monoclonal antibody; chemistry; fluorescence in situ hybridization; multicenter study; adjuvant chemotherapy; breast tumor; receptor, erbb-2; receptors, estrogen; estrogen receptor; anthracycline; body surface; polyclonal antibody |
| Journal Title: | New England Journal of Medicine |
| Volume: | 357 |
| Issue: | 15 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2007-10-11 |
| Start Page: | 1496 |
| End Page: | 1506 |
| Language: | English |
| DOI: | 10.1056/NEJMoa071167 |
| PUBMED: | 17928597 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 221" - "Export Date: 17 November 2011" - "CODEN: NEJMA" - "Source: Scopus" |
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