绝经后骨质疏松症妇女使用 lasofoxifene 的随机 PEARL 试验中的乳腺癌发病率。

Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women.

机构信息

Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.

出版信息

J Natl Cancer Inst. 2010 Nov 17;102(22):1706-15. doi: 10.1093/jnci/djq415. Epub 2010 Nov 4.

DOI:10.1093/jnci/djq415

PMID:21051656

Abstract

BACKGROUND

Currently available selective estrogen receptor modulators reduce the risk of breast cancer, but they are not widely used. In the Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene (PEARL) trial, lasofoxifene was shown to reduce the risk of estrogen receptor-positive (ER+) breast cancer, nonvertebral and vertebral fractures, coronary artery disease, and stroke, but the effects on total breast cancer (invasive and ductal carcinoma in situ, ER+ and estrogen receptor-negative [ER-]) and ER+ invasive breast cancer are unknown.

METHODS

Postmenopausal women (n = 8556) aged 59-80 years with low bone density and normal mammograms were randomly assigned to two doses of lasofoxifene (0.25 and 0.5 mg) or placebo. The primary endpoints of the PEARL trial were incidence of ER+ breast cancer and nonvertebral fractures at 5 years. A nested case-control study of 49 incident breast cancer case patients and 156 unaffected control subjects from the PEARL trial was performed to evaluate treatment effects on risk of total and ER+ invasive breast cancer by baseline serum estradiol and sex hormone-binding globulin levels using logistic regression models. Cox proportional hazards models were used to evaluate risk of total breast cancer and ER+ invasive breast cancer using intention-to-treat analysis. All statistical tests were two-sided.

RESULTS

Breast cancer was confirmed in 49 women. Compared with placebo, 0.5 mg of lasofoxifene statistically significantly reduced the risk of total breast cancer by 79% (hazard ratio = 0.21; 95% confidence interval [CI] = 0.08 to 0.55) and ER+ invasive breast cancer by 83% (hazard ratio = 0.17; 95% CI = 0.05 to 0.57). The effects of 0.5 mg of lasofoxifene on total breast cancer were similar regardless of Gail score, whereas the effects were markedly stronger for women with baseline estradiol levels greater than the median (odds ratio = 0.11; 95% CI = 0.02 to 0.51) vs those with levels less than the median (odds ratio = 0.78; 95% CI = 0.16 to 3.79; P(interaction) = .04).

CONCLUSION

A 0.5-mg dose of lasofoxifene appears to reduce the risks of both total and ER+ invasive breast cancer in postmenopausal women with osteoporosis.

摘要

背景

目前可用的选择性雌激素受体调节剂可降低乳腺癌风险，但并未广泛应用。在绝经后雌激素受体阳性（ER+）乳腺癌评估与雷洛昔芬预防（PEARL）试验中，雷洛昔芬显示可降低 ER+乳腺癌、非椎体和椎体骨折、冠心病和中风的风险，但对总乳腺癌（浸润性和导管原位癌，ER+和雌激素受体阴性[ER-]）和 ER+浸润性乳腺癌的影响尚不清楚。

方法

年龄在 59-80 岁之间、骨密度低且乳腺 X 线检查正常的绝经后妇女被随机分配至雷洛昔芬 0.25mg 和 0.5mg 两个剂量组或安慰剂组。PEARL 试验的主要终点为 5 年时 ER+乳腺癌和非椎体骨折的发生率。对来自 PEARL 试验的 49 例新发乳腺癌病例患者和 156 例未受影响的对照患者进行了巢式病例对照研究，通过基线血清雌二醇和性激素结合球蛋白水平，采用 logistic 回归模型评估治疗对总乳腺癌和 ER+浸润性乳腺癌的影响。采用意向治疗分析，Cox 比例风险模型评估总乳腺癌和 ER+浸润性乳腺癌的风险。所有统计检验均为双侧。

结果

49 名妇女被确诊患有乳腺癌。与安慰剂相比，雷洛昔芬 0.5mg 组总乳腺癌风险显著降低 79%（风险比=0.21；95%置信区间[CI]为 0.08 至 0.55），ER+浸润性乳腺癌风险降低 83%（风险比=0.17；95%CI 为 0.05 至 0.57）。雷洛昔芬 0.5mg 对总乳腺癌的作用与 Gail 评分无关，而对基线雌二醇水平高于中位数的妇女作用更强（比值比=0.11；95%CI 为 0.02 至 0.51），而对水平低于中位数的妇女作用较弱（比值比=0.78；95%CI 为 0.16 至 3.79；P（交互）=0.04）。