Cummings Steven R, Duong Tu, Kenyon Emily, Cauley Jane A, Whitehead Malcolm, Krueger Kathryn A
Coordinating Center, University of California, Suite 600, 74 New Montgomery St, San Francisco, CA 94105, USA.
JAMA. 2002 Jan 9;287(2):216-20. doi: 10.1001/jama.287.2.216.
As endogenous estradiol increases, risk of breast cancer increases. Raloxifene competes with endogenous estrogen for binding to estrogen receptors in breast tissue. A woman's estradiol level may alter the effects of raloxifene on breast cancer and other outcomes.
To test the hypothesis that raloxifene reduces breast cancer risk more in women with relatively high estradiol levels than in women with very low estradiol levels.
Analysis of the Multiple Outcomes of Raloxifene Evaluation, a randomized, double-blind, placebo-controlled trial conducted from 1994 to 1999.
One hundred eighty community settings and medical practices in 25 countries including the United States.
A total of 7290 postmenopausal women aged 80 years or younger with osteoporosis who had baseline serum estradiol concentrations measured by a central laboratory using a sensitive assay. Women with a history of breast cancer or estrogen use were excluded.
Participants were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene (n = 4843) or matching placebo (n = 2447) for 4 years.
New cases of histopathologically confirmed breast cancer in the treatment and placebo groups, stratified by estradiol levels.
In the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 6.8-fold higher rate of breast cancer (3.0% per 4 years; 95% confidence interval [CI], 1.8%-4.1%) than that of women with undetectable estradiol levels (0.6% per 4 years; 95% CI, 0%-1.1%; P =.005 for trend). Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% (95% CI, 53%-88%) lower than that of women with estradiol levels greater than 10 pmol/L in the placebo group (absolute rate reduction, 2.2% [95% CI, 1.0%-3.5%; number needed to treat = 45]). In contrast, women with undetectable estradiol levels had similar breast cancer risk whether or not they were treated with raloxifene (risk difference, -0.1%; 95% CI, -0.8% to 0.6%; P =.02 for the interaction). In this cohort, treating women with estradiol levels greater than 10 pmol/L with raloxifene for 4 years would have avoided 47% of breast cancer cases.
Measurement of estradiol level by sensitive assay in postmenopausal women identifies those at high risk of breast cancer who may benefit most from raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women.
随着内源性雌二醇水平升高，乳腺癌风险增加。雷洛昔芬与内源性雌激素竞争结合乳腺组织中的雌激素受体。女性的雌二醇水平可能会改变雷洛昔芬对乳腺癌及其他结局的影响。
检验以下假设：与雌二醇水平极低的女性相比，雷洛昔芬在雌二醇水平相对较高的女性中降低乳腺癌风险的作用更强。
对雷洛昔芬评估的多项结局进行分析，这是一项1994年至1999年进行的随机、双盲、安慰剂对照试验。
包括美国在内的25个国家的180个社区机构和医疗单位。
共有7290名80岁及以下患有骨质疏松症的绝经后女性，她们的基线血清雌二醇浓度由中心实验室采用灵敏检测法测定。排除有乳腺癌病史或使用过雌激素的女性。
参与者被随机分配接受每日60毫克或120毫克雷洛昔芬（n = 4843）或匹配的安慰剂（n = 2447），为期4年。
治疗组和安慰剂组经组织病理学确诊的乳腺癌新发病例，按雌二醇水平分层。
在安慰剂组中，雌二醇水平高于10皮摩尔/升（2.7皮克/毫升）的女性患乳腺癌的发生率（每4年3.0%；95%置信区间[CI]，1.8% - 4.1%）比雌二醇水平检测不到的女性（每4年0.6%；95%CI，0% - 1.1%；趋势P = 0.005）高6.8倍。雷洛昔芬组中雌二醇水平高于10皮摩尔/升的女性患乳腺癌的发生率比安慰剂组中雌二醇水平高于10皮摩尔/升的女性低76%（95%CI，53% - 88%）（绝对发生率降低2.2%[95%CI，1.0% - 3.5%；需治疗人数 = 45]）。相比之下，雌二醇水平检测不到的女性，无论是否接受雷洛昔芬治疗，患乳腺癌的风险相似（风险差异，-0.1%；95%CI，-0.8%至0.6%；交互作用P = 0.02）。在该队列中，用雷洛昔芬治疗雌二醇水平高于10皮摩尔/升的女性4年可避免47%的乳腺癌病例。
通过灵敏检测法测定绝经后女性的雌二醇水平，可识别出乳腺癌高危女性，这些女性可能从雷洛昔芬中获益最大。如果得到证实，这表明检测雌二醇并治疗雌二醇水平高的女性可大幅降低绝经后女性的乳腺癌发生率。
