HER2 and Response to Paclitaxel in Node-Positive Breast Cancer
Daniel F. Hayes, M.D., Ann D. Thor, M.D., Lynn G. Dressler, Dr.Ph., Donald Weaver, M.D., Susan Edgerton, M.A., David Cowan, B.A., Gloria Broadwater, M.S., Lori J. Goldstein, M.D., Silvana Martino, D.O., James N. Ingle, M.D., I. Craig Henderson, M.D., Larry Norton, M.D., Eric P. Winer, M.D., Clifford A. Hudis, M.D., Matthew J. Ellis, M.B., Ph.D., Donald A. Berry, Ph.D., for the Cancer and Leukemia Group B (CALGB) Investigators
Background The status of human epidermal growth factor receptortype 2 (HER2) in breast-cancer cells predicts clinical outcomesin women who receive adjuvant anthracycline-based chemotherapy.We hypothesized that HER2 positivity predicts a benefit fromadjuvant doxorubicin doses above standard levels, from the additionof paclitaxel after adjuvant chemotherapy with doxorubicin pluscyclophosphamide, or from both.
Methods We randomly selected 1500 women from 3121 women withnode-positive breast cancer who had been randomly assigned toreceive doxorubicin (60, 75, or 90 mg per square meter of body-surfacearea) plus cyclophosphamide (600 mg per square meter) for fourcycles, followed by four cycles of paclitaxel (175 mg per squaremeter) or observation. Tissue blocks from 1322 of these 1500women were available. Immunohistochemical analyses of thesetissue specimens for HER2 with the CB11 monoclonal antibodyagainst HER2 or with a polyclonal-antibody assay kit and fluorescencein situ hybridization for HER2 amplification were performed.
Results No interaction was observed between HER2 positivityand doxorubicin doses above 60 mg per square meter. HER2 positivitywas, however, associated with a significant benefit from paclitaxel.The interaction between HER2 positivity and the addition ofpaclitaxel to the treatment was associated with a hazard ratiofor recurrence of 0.59 (P=0.01). Patients with a HER2-positivebreast cancer benefited from paclitaxel, regardless of estrogen-receptorstatus, but paclitaxel did not benefit patients with HER2-negative,estrogen-receptor–positive cancers.
Conclusions The expression or amplification, or both, of HER2by a breast cancer is associated with a benefit from the additionof paclitaxel after adjuvant treatment with doxorubicin (<60mg per square meter) plus cyclophosphamide in node-positivebreast cancer, regardless of estrogen-receptor status. Patientswith HER2-negative, estrogen-receptor–positive, node-positivebreast cancer may gain little benefit from the administrationof paclitaxel after adjuvant chemotherapy with doxorubicin pluscyclophosphamide.
Source Information
From the University of Michigan Comprehensive Cancer Center, Ann Arbor (D.F.H.); the University of Colorado Comprehensive Cancer Center, Aurora (A.D.T., S.E.); the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill (L.G.D., D.C.); the University of Vermont Cancer Center, Fletcher Allen Health Care, Burlington (D.W.); Cancer and Leukemia Group B Statistical Center, Duke University, Durham, NC (G.B.); Fox Chase Comprehensive Cancer Center, Philadelphia (L.J.G.); the Angeles Clinic and Research Institute, Santa Monica, CA (S.M.); the Mayo Clinic, Rochester, MN (J.N.I.); the University of California at San Francisco, San Francisco (I.C.H.); Memorial Sloan-Kettering Cancer Center, New York (L.N., C.A.H.); the Dana–Farber Cancer Institute, Boston (E.P.W.); the Siteman Cancer Center, Washington University School of Medicine, St. Louis (M.J.E.); and the M.D. Anderson Cancer Center, Houston (D.A.B.).
Address reprint requests to Dr. Hayes at the Breast Oncology Program, 6312 Cancer Center, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48109, or at hayesdf{at}umich.edu.
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