Vogel V G
University of Pittsburgh Cancer Institute/Magee-Womens Hospital, Pennsylvania 15213-3180, USA.
Clin Cancer Res. 2001 Dec;7(12 Suppl):4413s-4418s; discussion 4411s-4412s.
Women who are at increased risk for developing breast cancer can be identified using quantitative risk assessment models that provide valid estimates of risk. The Breast Cancer Prevention Trial (BCPT, P-1) demonstrated that tamoxifen can reduce the incidence of both invasive and noninvasive breast cancer as well as of bone fractures in women at increased risk. These benefits accrue at the expense of increased risk of endometrial cancer, thromboses, cataracts, and possibly diminished quality of life in postmenopausal women. All premenopausal women with a 5-year risk of developing invasive breast cancer greater than 1.67% derive net benefit from using tamoxifen to reduce the risk. Subset analyses of older postmenopausal women taking raloxifene for the treatment of osteoporosis indicate reduction of breast cancer incidence by more than 70%. These findings led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to design and launch the STAR trial (P-2, the Study of Tamoxifen and Raloxifene). Eligible women are at least 35 years of age and postmenopausal, and they must have either lobular carcinoma in situ (LCIS) or a 5-year risk of invasive breast cancer of at least 1.67% as determined by the Gail model [M. H. Gail et al., J. Natl. Cancer Inst. (Bethesda), 81: 1879-1886, 1989]. Subjects are randomly assigned to receive either tamoxifen 20 mg or raloxifene 60 mg daily in a double-blind, double-dummy design. The trial is designed to recruit a total of 22,000 postmenopausal women and is powered to demonstrate superior efficacy of either agent or their equivalence in reducing the incidence of primary breast cancer. Additional end points will include the incidence of cardiovascular events and bone fractures. Thromboembolic events and endometrial cancer are the predicted toxicities. Ancillary studies of cognitive function will also be performed. Raloxifene should not be used for the reduction of breast cancer risk outside the context of the STAR trial.
可通过提供有效风险估计值的定量风险评估模型来识别乳腺癌发病风险增加的女性。乳腺癌预防试验（BCPT，P-1）表明，他莫昔芬可降低发病风险增加的女性患浸润性和非浸润性乳腺癌以及骨折的发生率。这些益处是以增加子宫内膜癌、血栓形成、白内障的风险以及可能降低绝经后女性生活质量为代价的。所有5年患浸润性乳腺癌风险大于1.67%的绝经前女性使用他莫昔芬降低风险可获得净益处。对服用雷洛昔芬治疗骨质疏松症的老年绝经后女性进行的亚组分析表明，乳腺癌发病率降低了70%以上。这些发现促使国家外科辅助乳腺和肠道项目（NSABP）设计并开展了STAR试验（P-2，他莫昔芬与雷洛昔芬研究）。符合条件的女性年龄至少35岁且已绝经，并且她们必须患有小叶原位癌（LCIS）或根据盖尔模型[M. H. 盖尔等人，《美国国家癌症研究所杂志》（贝塞斯达），81: 1879 - 1886，1989]确定的5年患浸润性乳腺癌风险至少为1.67%。受试者被随机分配，以双盲、双模拟设计每日接受20毫克他莫昔芬或60毫克雷洛昔芬。该试验旨在招募总共22,000名绝经后女性，其效能足以证明任何一种药物在降低原发性乳腺癌发病率方面的卓越疗效或它们的等效性。其他终点将包括心血管事件和骨折的发生率。血栓栓塞事件和子宫内膜癌是预计的毒性反应。还将进行认知功能的辅助研究。在STAR试验之外，雷洛昔芬不应被用于降低乳腺癌风险。
