Grady Deborah, Cauley Jane A, Geiger Mary Jane, Kornitzer Marcel, Mosca Lori, Collins Peter, Wenger Nanette K, Song Jingli, Mershon John, Barrett-Connor Elizabeth
University of California, San Francisco, and San Francisco VA Medical Center, San Francisco, CA 94115, USA.
J Natl Cancer Inst. 2008 Jun 18;100(12):854-61. doi: 10.1093/jnci/djn153. Epub 2008 Jun 10.
In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup.
Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided.
As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)-positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer.
Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis.
在雷洛昔芬用于心脏的试验中，10101名患有冠心病（CHD）或多种冠心病危险因素的绝经后女性被随机分配至雷洛昔芬60mg/天组或安慰剂组，并随访了5.6年的中位数时间。雷洛昔芬是一种选择性雌激素受体调节剂，被发现可降低浸润性乳腺癌和椎体骨折的风险，但不能降低心血管事件的风险。在此，我们按肿瘤特征、治疗持续时间和亚组提供关于乳腺癌发病率的更多细节。
报告的乳腺癌由一个独立委员会根据病历和病理报告进行判定。主要分析使用Cox比例风险模型，以首次发生乳腺癌的时间作为结局。亚组效应使用类似模型并带有亚组治疗项进行分析。所有统计检验均为双侧检验。
如先前报道，雷洛昔芬使浸润性乳腺癌的发病率降低了44%（风险比[HR]=0.56；95%置信区间[CI]=0.38至0.83；绝对风险降低为每1000名接受1年治疗的女性中有1.2例浸润性乳腺癌）。浸润性乳腺癌发病率较低反映出浸润性雌激素受体（ER）阳性肿瘤的发病率降低了55%（HR=0.45；95%CI=0.28至0.72）。然而，雷洛昔芬治疗并未降低非浸润性乳腺癌或浸润性ER阴性乳腺癌的发病率。浸润性乳腺癌发病率的降低在各亚组中相似，包括按年龄、体重指数、乳腺癌家族史、绝经后激素的既往使用情况以及浸润性乳腺癌的5年估计风险所定义的亚组。
无论女性的基线乳腺癌风险如何，雷洛昔芬均可降低浸润性ER阳性乳腺癌的风险，但不能降低非浸润性或ER阴性乳腺癌的风险。这些结果证实了雷洛昔芬评估的多项结果，这是一项先前在骨质疏松症女性中进行的随机试验的结果。
