A large, randomized trial of 9,779 patients compared DFS of postmenopausal women with hormone receptor–positive breast cancer between initial treatment with sequential tamoxifen for 2.5 to 3 years followed by exemestane for a total of 5 years versus exemestane alone for 5 years. The primary endpoints were DFS at 2.75 years and 5.0 years. Five-year DFS was 85% in the sequential group and 86% in the exemestane-alone group (HR, 0.97; 95% CI, 0.88–1.08; P = .60).[Level of evidence: 1iDii] The results of this trial support the use of exemestane, either sequentially after tamoxifen or as initial treatment for early-stage hormone receptor–positive breast cancer in postmenopausal women.
The mild androgen activity of exemestane prompted a randomized trial to evaluate whether exemestane might be preferable to anastrozole, in terms of its efficacy and toxicity, as upfront therapy for postmenopausal women diagnosed with hormone receptor-positive breast cancer.[Level of evidence: 1iiA] The MA27 (NCT00066573) trial randomly assigned 7,576 postmenopausal women to receive 5 years of anastrozole versus exemestane. At a median follow-up of 4.1 years, no difference in efficacy was seen.
Overview of Chemotherapy
Standard chemotherapy regimens for the adjuvant treatment of operable breast cancer that is given in the modern era are described in Table 6. There is no evidence favoring any regimen as superior to another. Therefore, any of these standard regimens is acceptable therapy.
Benefit of chemotherapy
Some of the most important data on the benefit of adjuvant chemotherapy came from the EBCTCG, which meets every 5 years to review data from global breast cancer trials. The year 2000 overview analysis (published in 2005) summarized the results of randomized adjuvant trials initiated by 1995. The analyses of adjuvant chemotherapy involved 28,764 women participating in 60 trials of combination chemotherapy (polychemotherapy) versus no chemotherapy, 14,470 women in 17 trials of anthracycline-containing versus CMF-type chemotherapy, and 6,125 women in 11 trials of longer versus shorter chemotherapy duration.
For women younger than 50 years, polychemotherapy reduced the annual risk of disease relapse and death from breast cancer by 37% and 30%, respectively. This translated into a 10% absolute improvement in 15-year survival (HR, 42% vs. 32%). For women aged 50 to 69 years, the annual risk of relapse or death from breast cancer was decreased by 19% and 12%, respectively. This translated into a 3% absolute gain in 15-year survival (HR, 50% vs. 47%). The absolute gain in survival for polychemotherapy versus no adjuvant therapy in women younger than 50 was twice as great at 15 years as it was at 5 years (10% vs. 4.7%), while the main effect on disease recurrence was seen in the first 5 years. The 15-year cumulative reduction in mortality from 6 months of an anthracycline-based regimen (e.g., fluorouracil, doxorubicin, cyclophosphamide [FAC] or fluorouracil, epirubicin, cyclophosphamide [FEC]) was 38% in women younger than 50 years, and 20% in those aged 50 to 60 years. The meta-analysis also showed that the reduction in risk of recurrence was similar in the presence or absence of tamoxifen, irrespective of age (<50 years vs. 50–69 years), though the result did not attain statistical significance in those randomly assigned women younger than 50 years. This finding, however, is most likely the result of the relatively small number of younger women in trials of combined chemoendocrine therapy. Few women older than 70 years had been studied, and specific conclusions could not be reached in this group. Importantly, these data were derived from clinical trials in which patients were not selected for adjuvant therapy according to ER status, and they were initiated before the advent of taxane-containing, dose-dense, or trastuzumab-based therapy. As a result, they may not reflect treatment outcomes based on evolving treatment patterns.
Results of individual trials are generally in agreement with the conclusions of the meta-analysis. The NSABP-B-13 study demonstrated a benefit for chemotherapy with sequential methotrexate and 5-FU versus surgery alone in patients with node-negative, ER-negative tumors.[93,94,161,162][Level of evidence: 1iiA]