Pharmaceuticals that cause mammary gland tumors in animals: findings in women.
Pharmaceuticals that cause mammary gland tumors in animals: findings in women.
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DOI：
10.1007/s10549-008-0123-1
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发表时间：
2009-07
影响因子：
3.8
通讯作者：
Habel, Laurel A.
中科院分区：
文献类型：
--
作者：
Friedman, Gary D.;Jiang, Sheng-Fang;Udaltsova, Natalia;Chan, James;Quesenberry, Charles P., Jr.;Habel, Laurel A.
关键词：
通过在综合医疗保健计划中的两个队列中使用嵌套病例对照分析以及处方记录，评估了八种在实验动物中产生乳腺肿瘤的药物的女性患乳腺癌的风险。这两个队列是：1) 早期队列：1969-1973 年接受处方的 78,118 名女性会员，其中 2,467 人罹患乳腺癌；2) 后期队列：1994-2006 年接受处方的 3,289,408 名女性会员，其中 24,528 人罹患乳腺癌。最长的随访时间截至 2006 年 6 月 30 日。十名随机选择的同期对照女性几乎与每个病例年龄匹配。通过条件逻辑回归估计相对风险。病例查明滞后两年，或者不滞后并按收到的处方数量细分。一些分析针对激素的使用进行了控制，并进行了敏感性分析以估计不受控制的混杂因素的影响。在后来的队列中，速尿和甲硝唑显示出统计学上显着但相对风险很小的增加（范围从 1.07 到 1.13）。其中，只有呋塞米在早期队列中显示出风险增加：假设不受控制的阳性混杂因素，2 年滞后相对风险为 1.66（95% 置信区间 1.23-2.24）或低至 0.97。灰黄霉素在后来的队列中显示出显着增加：三种或更多处方的相对风险为 1.48 (1.08-2.03) 或低至 1.23，假设在早期队列中注意到不受控制的阳性混杂和非显着增加。我们的研究结果受到两个队列的不一致以及我们无法直接控制大多数已确定的乳腺癌风险因素的限制。尽管尚无定论，但我们的研究结果表明需要对呋塞米和灰黄霉素进行更多研究。
Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: 1) earlier cohort: 78,118 female members who received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and 2) later cohort: 3,289,408 female members who received prescriptions in 1994-2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30, 2006. Ten randomly selected concurrent control women were age-matched to almost every case. Relative risks were estimated by conditional logistic regression. Case ascertainment was lagged by two years, or unlagged and subdivided by number of prescriptions received. Some analyses were controlled for hormone use and sensitivity analyses were conducted to estimate the effects of uncontrolled confounding. In the later cohort furosemide, and metronidazole showed statistically significant but very small increases in relative risk (ranging from 1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed significant increases in the later cohort: relative risk for three or more prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive confounding and non-significant increases were noted in the earlier cohort. Our findings are limited by their inconsistency across the two cohorts and our inability to directly control for most established breast cancer risk factors. Although inconclusive, our findings suggest a need for more research on furosemide and griseofulvin.
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