Longer Therapy, Iatrogenic Amenorrhea, and Survival in Early Breast Cancer

Volume 362:2053-2065 June 3, 2010 Number 22

Longer Therapy, Iatrogenic Amenorrhea, and Survival in Early Breast Cancer
Sandra M. Swain, M.D., Jong-Hyeon Jeong, Ph.D., Charles E. Geyer, Jr., M.D., Joseph P. Costantino, Dr.P.H., Eduardo R. Pajon, M.D., Louis Fehrenbacher, M.D., James N. Atkins, M.D., Jonathan Polikoff, M.D., Victor G. Vogel, M.D., M.H.S., John K. Erban, M.D., Priya Rastogi, M.D., Robert B. Livingston, M.D., Edith A. Perez, M.D., Eleftherios P. Mamounas, M.D., M.P.H., Stephanie R. Land, Ph.D., Patricia A. Ganz, M.D., and Norman Wolmark, M.D.

ABSTRACT

Background Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node–positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.

Methods We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin–docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin–docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.

Results At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin–docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin–docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin–docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.

Conclusions Sequential ACT improved disease-free survival as compared with doxorubicin–docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin–docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status. (ClinicalTrials.gov number, NCT00003782 [ClinicalTrials.gov] .)



Source Information

From the National Surgical Adjuvant Breast and Bowel Project (NSABP) (S.M.S., C.E.G., E.R.P., L.F., J.N.A., J.P., V.G.V., P.R., E.P.M., S.R.L., P.A.G., N.W.); Washington Cancer Institute at Washington Hospital Center, Washington, DC (S.M.S.); NSABP Biostatistical Center and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh (J.-H.J., J.P.C., S.R.L.), Allegheny General Hospital (C.E.G., N.W.), and University of Pittsburgh Cancer Institute (V.G.V., P.R.) — all in Pittsburgh; Colorado Cancer Research Program, Denver (E.R.P.); Kaiser Permanente Northern California, Vallejo, CA (L.F.); Southeast Cancer Control Consortium, Clinical Cancer Oncology Program, Goldsboro, NC (J.N.A.); Southern California Kaiser Permanente, San Diego (J.P.); American Cancer Society, Atlanta (V.G.V.); Massachusetts General Hospital Cancer Center and Harvard Medical School — both in Boston (J.K.E.); the Eastern Cooperative Oncology Group, Philadelphia (J.K.E.); Arizona Cancer Center, University of Arizona, Tucson (R.B.L.); the Southwest Oncology Group, Ann Arbor, MI (R.B.L.); Mayo Clinic, Jacksonville, Jacksonville, FL (E.A.P.); the North Central Cancer Treatment Group, Rochester, MN (E.A.P.); Aultman Health Foundation, Canton, OH (E.P.M.); and the University of California Los Angeles School of Medicine and Public Health, Jonsson Comprehensive Cancer Center, Los Angeles (P.A.G.).

Address reprint requests to Dr. Swain at Washington Cancer Institute, Washington Hospital Center, 110 Irving St. NW, Washington, DC 20010, or at sandra.m.swain@medstar.net.

abstract:
http://content.nejm.org/cgi/content/abstract/362/22/2053

full-text:
http://content.nejm.org/cgi/content/full/362/22/2053