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Related Article: Editorial, N Engl J Med 2010 :362 ;2053 -2124 .
Chemotherapy regimens that combine anthracyclines and taxanes with other agents such as cyclophosphamide result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer.1 ,2 The contribution of cyclophosphamide to these regimens has not been defined. Initial evaluations of taxanes in the adjuvant setting used a sequential approach of administration after completion of the anthracycline-based regimen. Phase 3 trials in advanced breast cancer have shown superiority with a doxorubicin-docetaxel combination as compared with doxorubicin-cyclophosphamide and with doxorubicin, cyclophosphamide, and docetaxel (ACT, also known as the TAC regimen), and as compared with fluorouracil, doxorubicin, and cyclophosphamide.3 ,4 These studies provided the rationale for the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-30 trial.
This trial was designed to compare the sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel (sequential ACT) with the doxorubicin-docetaxel combination and with the concurrent regimen of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT), while keeping the number of cycles of doxorubicin and docetaxel the same in all three groups. Specific questions addressed in this trial were whether four cycles of the concurrent-ACT regimen would improve overall survival and disease-free survival as compared with the sequential regimen and whether a four-cycle regimen of doxorubicin-docetaxel without cyclophosphamide would be at least as effective as four cycles of concurrent ACT. The development of amenorrhea during and after adjuvant chemotherapy has been associated with clinically important effects on symptoms and quality of life in women with early breast cancer.5 To assess the effect of amenorrhea on the outcome end points, we prospectively documented menstrual status after therapy in premenopausal patients.
Methods
Patients
Women were eligible for randomization if they presented with invasive adenocarcinoma (tumor stage T1, T2, or T3, clinical nodal stage N0 or N1, and metastasis stage M0)6 and had undergone primary surgery with total mastectomy or lumpectomy plus axillary nodal dissection with margins of resection that were histologically free of invasive tumor or ductal carcinoma in situ. Histologic evidence of tumor in at least one lymph node was required. Randomization must have occurred within 84 days after the final surgery. Analysis of estrogen-receptor (ER) and progesterone-receptor (PR) expression and the intended plan for radiotherapy were required before entry...