Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.
Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.
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DOI：
10.1016/s0140-6736(12)61963-1
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发表时间：
2013-03-09
期刊：
影响因子：
168.9
通讯作者：
Peto, Richard
中科院分区：
文献类型：
--
作者：
Davies, Christina;Pan, Hongchao;Godwin, Jon;Gray, Richard;Arriagada, Rodrigo;Raina, Vinod;Abraham, Mirta;Medeiros Alencar, Victor Hugo;Badran, Atef;Bonfill, Xavier;Bradbury, Joan;Clarke, Michael;Collins, Rory;Davis, Susan R.;Delmestri, Antonella;Forbes, John F.;Haddad, Peiman;Hou, Ming-Feng;Inbar, Moshe;Khaled, Hussein;Kielanowska, Joanna;Kwan, Wing-Hong;Mathew, Beela S.;Mittra, Indraneel;Mueller, Bettina;Nicolucci, Antonio;Peralta, Octavio;Pernas, Fany;Petruzelka, Lubos;Pienkowski, Tadeusz;Radhika, Ramachandran;Rajan, Balakrishnan;Rubach, Maryna T.;Tort, Sera;Urrutia, Gerard;Valentini, Miriam;Wang, Yaochen;Peto, Richard
对于雌激素受体（ER）阳性的早期乳腺癌患者，使用他莫昔芬治疗5年可显著降低诊断后前15年的乳腺癌死亡率。我们的目的是评估继续他莫昔芬治疗10年而不是5年后停止治疗的进一步影响。在全球辅助他莫昔芬：更长时间对抗更短时间（ATLAS）试验中，12，894名已完成5年他莫昔芬治疗的早期乳腺癌女性被随机分配继续他莫昔芬治疗至10年或在5年时停止（开放对照）。 分配（1：1）由中央计算机使用最小化。入组后（1996年至2005年），每年的随访表记录任何复发，第二次癌症，住院或死亡。我们报告了6846例ER阳性乳腺癌患者的乳腺癌预后，以及所有女性（ER阳性、阴性或未知状态）的副作用。长期跟踪仍在继续。本研究已注册，编号ISRCTN 19652633。在ER阳性乳腺癌患者中，继续使用他莫昔芬可降低乳腺癌复发风险（3428例继续治疗的妇女中有617例复发，3418例对照组中有711例复发，p= 0.002），乳腺癌死亡率降低（331例死亡vs 397例死亡，p= 0.01），总死亡率降低（639例死亡vs 722例死亡，p= 0.01）。与10年后相比，10年前乳腺癌不良结局的减少似乎不那么极端（5-9年复发率比[RR] 0·90 [95% CI 0·79-1·02]，以后0·75 [0·62-0·90]; 5-9岁乳腺癌死亡率RR为0.97 [0.79 - 1.18]，以后为0.71 [0.58 - 0.88]）。5-14年期间，分配继续的女性的累积复发风险为21.4%，对照组为25.1%;分配继续的女性5-14年期间的乳腺癌死亡率为12.2%，对照组为15.0%（绝对死亡率降低2.8%）。在1248例ER阴性乳腺癌患者中，治疗分配似乎对乳腺癌预后没有影响，而在4800例ER状态未知的女性中，治疗分配对乳腺癌预后有中等影响。在所有12894名妇女中，乳腺癌以外的原因导致的无复发死亡率几乎没有受到影响（6454名妇女中有691名死亡无复发，6440名对照组中有679名死亡; RR 0.99 [0.89 - 1.10]; p= 0.84）。 发病率（住院或死亡）特定疾病的RR率如下：肺栓塞1·87（95% CI 1.13 - 3.07，p= 0.01 [包括两个治疗组的0.2%死亡率]），卒中1.06（0.83 - 1.36），缺血性心脏病0.76（0.60 - 0.95，p= 0.02），子宫内膜癌1.74（1.30 - 2.34，p= 0.0002）。在5-14岁期间，分配继续治疗的妇女患子宫内膜癌的累积风险为3.1%（死亡率0.4%），对照组为1.6%（死亡率0.2%）（绝对死亡率增加0.2%）。对于ER阳性疾病的女性，继续使用他莫昔芬至10年而不是在5年时停止使用，可以进一步降低复发率和死亡率，特别是在10年后。这些结果，以及之前5年他莫昔芬治疗与不治疗的试验结果，表明10年他莫昔芬治疗可以使诊断后第二个十年的乳腺癌死亡率大约减半。英国癌症研究所、英国医学研究理事会、英国阿斯利康、美国陆军、欧盟生物医学。
For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.