Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Leeds Institute of Health Science, University of Leeds, Leeds, UK.
Ann Oncol. 2018 Feb 1;29(2):504-509. doi: 10.1093/annonc/mdx713.
Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS)-II prevention and ductal carcinoma in situ (DCIS) trials, and its association with early symptoms.
In the prevention trial, 3864 postmenopausal women were randomized to placebo versus anastrozole. A total of 2980 postmenopausal women with DCIS were randomized to tamoxifen versus anastrozole. Adherence to trial medication was calculated using the Kaplan-Meier method and all P-values were two-sided.
In the prevention trial, adherence was 65.8% [anastrozole (65.7%) versus placebo (65.9%); HR = 0.97 (0.87-1.09), P = 0.6]. Adherence was lower for those reporting arthralgia in the placebo group (P = 0.02) or gynecological symptoms in the anastrozole group (P = 0.003), compared with those not reporting these symptoms at 6 months. In the DCIS study, adherence was 66.7% [anastrozole (67.5%) versus tamoxifen (65.8%); HR = 1.06 (0.94-1.20), P = 0.4]. Hot flashes were associated with greater adherence in the anastrozole arm (P = 0.02). In both studies, symptoms were mostly mild or moderately severe, and adherence decreased with increasing severity for most symptoms. Drop-outs were highest in the first 1.5 years of therapy in both trials.
In the IBIS-II prevention and DCIS trials, over two-thirds of women were adherent to therapy, with no differences by treatment groups. Participants who reported specific symptoms in the IBIS-II prevention trial had a small but significant effect on adherence, which strengthened as severity increased. Strategies to promote adherence should target the first year of preventive therapy.
阿那曲唑可降低高危女性的乳腺癌风险，但在临床实践中实施预防治疗较为困难。在此，我们评估了国际乳腺癌干预研究（IBIS）-II 预防和导管原位癌（DCIS）试验中阿那曲唑的依从性及其与早期症状的关系。
在预防试验中，3864 名绝经后妇女被随机分配至安慰剂组或阿那曲唑组。2980 名绝经后 DCIS 妇女被随机分配至他莫昔芬组或阿那曲唑组。采用 Kaplan-Meier 法计算试验药物的依从性，所有 P 值均为双侧。
在预防试验中，依从率为 65.8%[阿那曲唑（65.7%）与安慰剂（65.9%）；HR=0.97（0.87-1.09），P=0.6]。与 6 个月时无关节痛报告的患者相比，安慰剂组报告关节痛（P=0.02）或阿那曲唑组报告妇科症状（P=0.003）的患者依从性较低。在 DCIS 研究中，依从率为 66.7%[阿那曲唑（67.5%）与他莫昔芬（65.8%）；HR=1.06（0.94-1.20），P=0.4]。阿那曲唑组出现热潮红与更高的依从性相关（P=0.02）。在两项研究中，症状大多为轻度或中度严重，大多数症状的严重程度与依从性呈负相关。在两项试验中，停药率均在治疗的前 1.5 年最高。
在 IBIS-II 预防和 DCIS 试验中，超过三分之二的女性对治疗有依从性，治疗组之间无差异。在 IBIS-II 预防试验中报告特定症状的参与者对依从性有很小但显著的影响，随着症状严重程度的增加而增强。促进依从性的策略应针对预防治疗的第一年。
