HER2 &  Response to Paclitaxel in Node-Positive Breast Cancer

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 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.


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.


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.


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.

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@umich.edu.

NEJM, Volume 357:1496-1506 October 11, 2007 Number 15

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