Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.
Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.
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DOI：
10.1056/nejmoa1604700
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发表时间：
2016-07-21
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影响因子：
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通讯作者：
Parulekar WR
中科院分区：
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作者：
Goss PE;Ingle JN;Pritchard KI;Robert NJ;Muss H;Gralow J;Gelmon K;Whelan T;Strasser-Weippl K;Rubin S;Sturtz K;Wolff AC;Winer E;Hudis C;Stopeck A;Beck JT;Kaur JS;Whelan K;Tu D;Parulekar WR
芳香化酶抑制剂治疗5年作为前期单药治疗或在他莫昔芬治疗后是绝经后妇女乳腺癌受体阳性早期乳腺癌的治疗选择。将芳香化酶抑制剂的治疗延长至10年可能会进一步降低乳腺癌复发的风险。我们进行了一项双盲、安慰剂对照试验，以评估来曲唑延长使用5年的效果。我们的主要终点是无病生存期。我们招募了1918名女性。在中位随访6.3年后，有165例事件涉及疾病复发或对侧乳腺癌的发生（来曲唑组67例，安慰剂组98例），200例死亡（每组100例）。5年无病生存率为95%（95%置信区间[CI]，93 - 96），来曲唑和91%（95% CI; 89 - 93）安慰剂组（疾病复发或发生对侧乳腺癌的风险比为0.66;根据淋巴结状态、既往辅助化疗、芳香化酶抑制剂治疗末次给药间隔和他莫昔芬治疗持续时间分层的双侧对数秩检验，P = 0.01。来曲唑组5年总生存率为93%（95%CI，92 - 95），安慰剂组为94%（95%CI，92 - 95）（风险比，0.97; P = 0.83）。来曲唑组对侧乳腺癌的年发病率为0.21%（95%CI，0.10 - 0.32），安慰剂组为0.49%（95%CI，0.32 - 0.67）（风险比，0.42; P = 0.007）。与接受安慰剂的患者相比，接受来曲唑的患者更频繁地发生与骨骼相关的毒性作用，包括骨痛、骨折和新发骨质疏松症的发生率更高。来曲唑组和安慰剂组在大多数生活质量子量表上的评分无显著差异。与安慰剂组相比，芳香酶抑制剂辅助治疗延长至10年，无病生存率显著提高，对侧乳腺癌发病率降低，但芳香酶抑制剂组的总生存率并不高于安慰剂组。（由加拿大癌症协会和其他人资助; ClinicalTrials.gov编号，NCT 00003140和NCT 00754845。
Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor–positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P = 0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P = 0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P = 0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contra-lateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.)