Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer

Sandra M. Swain, Jong Hyeon Jeong, Charles E. Geyer, Joseph P. Costantino, Eduardo R. Pajon, Louis Fehrenbacher, James N. Atkins, Jonathan Polikoff, Victor G. Vogel, John K. Erban, Priya Rastogi, Robert B. Livingston, Edith A. Perez, Eleftherios P. Mamounas, Stephanie R. Land, Patricia A. Ganz, Norman Wolmark

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235 Scopus citations

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.).

Original languageEnglish (US)
Pages (from-to)2053-2065
Number of pages13
JournalNew England Journal of Medicine
Volume362
Issue number22
DOIs
StatePublished - Jun 3 2010

ASJC Scopus subject areas

  • Medicine(all)

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    Swain, S. M., Jeong, J. H., Geyer, C. E., Costantino, J. P., Pajon, E. R., Fehrenbacher, L., Atkins, J. N., Polikoff, J., Vogel, V. G., Erban, J. K., Rastogi, P., Livingston, R. B., Perez, E. A., Mamounas, E. P., Land, S. R., Ganz, P. A., & Wolmark, N. (2010). Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. New England Journal of Medicine, 362(22), 2053-2065. https://doi.org/10.1056/NEJMoa0909638