NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

docetaxel given by either an every-3-week schedule or a weekly schedule. 323-325 At a median 63.8 months of follow-up, no statistically significant differences in DFS or OS were observed when comparing paclitaxel to docetaxel or weekly versus every-3-week administration. In a secondary series of comparisons, weekly paclitaxel was superior to every-3-week paclitaxel in DFS (HR, 1.27; 95% CI, 1.03– 1.57; P = .006) and OS (HR, 1.32; 95% CI, 1.02–1.72; P = .01), and every-3-week docetaxel was superior to every-3-week paclitaxel in DFS (HR, 1.23; 95% CI, 1.00–1.52; P = .02) but not in OS. 325 Based on these results, as well as the findings from the CALGB trial 9741 that showed dose-dense AC followed by paclitaxel every 2 weeks to have a survival benefit when compared with the regimen of AC followed by every-3-week paclitaxel, 322 the every-3-week paclitaxel regimen has been removed from the guidelines. Combination TC was compared with AC chemotherapy in a trial that randomized 1016 women with stage I to III breast cancer. 326 At a median follow-up of 7 years, overall DFS (81% vs. 75%; HR, 0.74; 95% CI, 0.56–0.98; P = .033) and OS (87% vs. 82%; HR, 0.69; 95% CI, 0.50–0.97; P = .032) were significantly improved with TC compared with AC. Other Regimens Other regimens included in the guidelines are: AC; fluorouracil, doxorubicin, and cyclophosphamide (FAC/CAF); cyclophosphamide, epirubicin, and fluorouracil (FEC/CEF); epirubicin and cyclophosphamide (EC); CMF; AC with sequential docetaxel administered every 3 weeks; AC with sequential weekly paclitaxel; FEC/CEF followed by docetaxel or weekly paclitaxel; FAC followed by weekly paclitaxel; and docetaxel, doxorubicin, and cyclophosphamide (TAC).

The AC regimen for four cycles has been studied in randomized trials, resulting in relapse-free survival and OS equivalent to CMF chemotherapy. 327-329 No benefit from dose escalation of either doxorubicin or cyclophosphamide was shown. 320,330 Studies of CMF chemotherapy versus no chemotherapy have shown DFS and OS advantages with CMF chemotherapy. 3,331 Studies using CAF/FAC chemotherapy have shown that the use of full-dose chemotherapy regimens is important. 332 In the EBCTCG overview of polychemotherapy, comparison of anthracycline-containing regimens with CMF showed a 12% further reduction in the annual odds of recurrence ( P = .006) and an 11% further reduction in the annual odds of death ( P = .02) with anthracycline-containing regimens. 331 Based on these data, the Panel qualified the appropriate chemotherapy regimens by the statement that anthracycline-containing regimens are preferred for node-positive patients. The EBCTCG analysis, however, did not consider the potential interaction between HER2 tumor status and efficacy of anthracycline-containing versus CMF chemotherapy regimens. Retrospective analysis has suggested that the superiority of anthracycline-containing chemotherapy may be limited to the treatment of those breast cancers that are HER2 - positive. 214,216,219,259,333-335 The retrospective finding across several clinical trials that anthracycline-based chemotherapy may be more efficacious in patients whose tumors are HER2 - positive has led to a footnote stating that anthracycline-based chemotherapy may be superior to non-anthracycline-containing regimens in the adjuvant treatment of such patients. Two randomized prospective trials of CEF chemotherapy in ALN-positive breast cancer are available. In one trial, premenopausal

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