Nichols Hazel B, DeRoo Lisa A, Scharf Daniel R, Sandler Dale P
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC (HBN); Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway (LAD); Westat, Durham, NC (DS); Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC (DPS).
J Natl Cancer Inst. 2014 Dec 3;107(1):354. doi: 10.1093/jnci/dju354. Print 2015 Jan.
Tamoxifen has been US Food and Drug Administration-approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer.
This research was conducted within The Sister Study, a cohort of 50884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009. Eligible women were breast cancer-free at enrollment and had a sister who had been diagnosed with breast cancer. Participants reported tamoxifen use, ages started and stopped taking tamoxifen, and total duration of use at enrollment. We identified 788 tamoxifen users and 3131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer). Characteristics associated with tamoxifen initiation were evaluated with multivariable conditional logistic regression. All statistical tests were two-sided.
Based on published risk-benefit indices, 20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects. After 4.5 years, 46% of women had discontinued tamoxifen.
While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.
自1998年以来，他莫昔芬已获美国食品药品监督管理局批准用于乳腺癌的一级预防，但尚未得到广泛应用，部分原因是严重副作用风险增加。对于在临床试验之外使用化学预防的女性的风险效益概况知之甚少。我们在一大群有乳腺癌一级家族史的女性中，研究了与开始和停止使用他莫昔芬进行乳腺癌一级预防相关的特征。
本研究在“姐妹研究”中进行，该队列包括2003年至2009年招募的50884名年龄在35至74岁之间的美国和波多黎各女性。符合条件的女性在入组时无乳腺癌，且有一个被诊断患有乳腺癌的姐妹。参与者报告了他莫昔芬的使用情况、开始和停止服用他莫昔芬的年龄以及入组时的总使用时长。我们确定了788名他莫昔芬使用者和3131名年龄和入组年份相匹配且无禁忌因素（中风、短暂性脑缺血发作、白内障、子宫内膜癌或子宫癌）病史的非使用者。使用多变量条件逻辑回归评估与开始使用他莫昔芬相关的特征。所有统计检验均为双侧检验。
根据已发表的风险效益指数，20%使用他莫昔芬的女性没有充分证据表明他莫昔芬的益处超过严重副作用的风险。4.5年后，46%的女性停止使用他莫昔芬。
虽然大多数使用他莫昔芬进行乳腺癌一级预防的女性可能会受益，但在五年前大量停止使用他莫昔芬以及有严重副作用风险的女性使用该药可能会削弱乳腺癌预防的益处。
