Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Lancet. 2013 May 25;381(9880):1827-34. doi: 10.1016/S0140-6736(13)60140-3. Epub 2013 Apr 30.
Tamoxifen and raloxifene reduce the risk of breast cancer in women at elevated risk of disease, but the duration of the effect is unknown. We assessed the effectiveness of selective oestrogen receptor modulators (SERMs) on breast cancer incidence.
We did a meta-analysis with individual participant data from nine prevention trials comparing four selective oestrogen receptor modulators (SERMs; tamoxifen, raloxifene, arzoxifene, and lasofoxifene) with placebo, or in one study with tamoxifen. Our primary endpoint was incidence of all breast cancer (including ductal carcinoma in situ) during a 10 year follow-up period. Analysis was by intention to treat.
We analysed data for 83,399 women with 306,617 women-years of follow-up. Median follow-up was 65 months (IQR 54-93). Overall, we noted a 38% reduction (hazard ratio [HR] 0·62, 95% CI 0·56-0·69) in breast cancer incidence, and 42 women would need to be treated to prevent one breast cancer event in the first 10 years of follow-up. The reduction was larger in the first 5 years of follow-up than in years 5-10 (42%, HR 0·58, 0·51-0·66; p<0·0001 vs 25%, 0·75, 0·61-0·93; p=0·007), but we noted no heterogeneity between time periods. Thromboembolic events were significantly increased with all SERMs (odds ratio 1·73, 95% CI 1·47-2·05; p<0·0001). We recorded a significant reduction of 34% in vertebral fractures (0·66, 0·59-0·73), but only a small effect for non-vertebral fractures (0·93, 0·87-0·99).
For all SERMs, incidence of invasive oestrogen (ER)-positive breast cancer was reduced both during treatment and for at least 5 years after completion. Similar to other preventive interventions, careful consideration of risks and benefits is needed to identify women who are most likely to benefit from these drugs.
Cancer Research UK.
他莫昔芬和雷洛昔芬可降低高危女性乳腺癌的发病风险，但作用持续时间尚不清楚。我们评估了选择性雌激素受体调节剂（SERMs）对乳腺癌发病的影响。
我们对 9 项预防试验的个体参与者数据进行了荟萃分析，比较了 4 种选择性雌激素受体调节剂（SERMs；他莫昔芬、雷洛昔芬、阿佐昔芬和拉索昔芬）与安慰剂，或在一项研究中与他莫昔芬比较。我们的主要终点是 10 年随访期间所有乳腺癌（包括导管原位癌）的发病率。分析采用意向治疗。
我们分析了 83399 名女性的数据，随访 306617 人年。中位随访时间为 65 个月（IQR 54-93）。总体而言，我们发现乳腺癌发病率降低了 38%（风险比[HR]0.62，95%CI 0.56-0.69），随访的前 10 年中每治疗 42 例患者即可预防 1 例乳腺癌事件。在随访的前 5 年，乳腺癌发病率的降低幅度大于第 5 至 10 年（42%，HR 0.58，0.51-0.66；p<0.0001 与 25%，0.75，0.61-0.93；p=0.007），但我们没有观察到两个时间段之间存在异质性。所有 SERMs 的血栓栓塞事件发生率均显著增加（比值比 1.73，95%CI 1.47-2.05；p<0.0001）。我们发现椎体骨折减少了 34%（0.66，0.59-0.73），但非椎体骨折的影响较小（0.93，0.87-0.99）。
所有 SERMs 的侵袭性雌激素（ER）阳性乳腺癌的发病率在治疗期间以及治疗结束后至少 5 年均降低。与其他预防干预措施类似，需要仔细考虑风险和获益，以确定最有可能从这些药物中获益的女性。
英国癌症研究协会。
