NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

reduction in risk of progression, possibly due to a “carryover effect.” The reduction in risk of recurrence was 0.90 (95% CI, 0.79–1.02) during 5 to 9 years of tamoxifen treatment and 0.75 (0.62–0.90) after 10 years. Furthermore, reduced mortality was apparent after completion of 10 years of treatment with tamoxifen. With regards to toxicity, the most important adverse effects noted in all women in ATLAS were an increased risk of endometrial cancer after treatment with 10 years of tamoxifen and pulmonary embolism. The recurrence rate ratios for incidence of adverse events (hospitalization or death) were: pulmonary embolus 1.87 (95% CI, 1.13–3.07, P = .01 [including 0.2% mortality in both treatment groups]), stroke 1.06 (0.83–1.36), ischemic heart disease 0.76 (0.60–0.95, P = .02), and endometrial cancer 1.74 (1.30– 2.34, P = .0002). The cumulative risk for endometrial cancers during 5 to 14 years was 3.1%, with a mortality of 0.4% associated with endometrial cancer, higher than what was noted in the control group of patients receiving only 5 years of therapy (cumulative risk: 1.6%; mortality: 0.2%). 265 Results are expected in the near future of other ongoing trials of extended tamoxifen, such as the aTTom trial of 5 years versus 10 years tamoxifen with 7000 women, are expected in the near future. Preliminary results of this trial have shown that continuation of tamoxifen beyond 5 years resulted in a non-significant reduction in recurrences. 266 The role of adjuvant ovarian ablation or suppression in premenopausal women with hormone receptor-positive breast cancer is incompletely defined. 267-269 Ovarian ablation may be accomplished by surgical oophorectomy or by ovarian irradiation. Ovarian suppression utilizes luteinizing hormone-releasing hormone (LH-RH) agonists that result in suppression of luteinizing hormone (LH) and release of follicle stimulating hormone (FSH) from the pituitary and reduction in ovarian

estrogen production. Available LH-RH agonists in the United States include goserelin and leuprolide and, when used for ovarian suppression, both agents should be given as monthly injections. The EBCTCG performed a meta-analysis of randomized studies of ovarian ablation or suppression alone versus no adjuvant treatment in women >50 years, with many of the subjects in the trials unselected based upon hormone receptor status. In this study there were reductions in the annual odds of recurrence and of death favoring ovarian ablation/suppression over no adjuvant treatment (age <40 years: 25% reduction in recurrence rate and 29% reduction in death rate; age 40–49 years: 29% reduction in recurrence rate and 29% reduction in death rate). 268 Analysis of ovarian suppression versus no adjuvant therapy did not demonstrate significant reduction in recurrence (HR reduction, 28.4, 95% CI, 50.5– 3.5; P = .08) or death (HR reduction, 22, 95% CI, 4.1– 6.4; P = .11). 270 Studies in premenopausal women of ovarian ablation or suppression alone versus CMF chemotherapy alone generally demonstrate similar antitumor efficacy in patients with hormone receptor-positive tumors and superior outcomes with CMF in patients with hormone receptor-negative tumors. 270-278 There is also the suggestion that the benefits to ovarian suppression/ablation may be greater in the younger premenopausal group. Studies in premenopausal women of ovarian ablation/suppression plus tamoxifen versus chemotherapy alone generally demonstrate no difference in rates of recurrence or survival. 268,279,280 A large intergroup study in premenopausal women with hormone receptor-positive, node-positive breast cancer studied adjuvant CAF (cyclophosphamide/doxorubicin/5-fluorouracil) chemotherapy versus

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