Marshall Sarah F, Bernstein Leslie, Anton-Culver Hoda, Deapen Dennis, Horn-Ross Pamela L, Mohrenweiser Harvey, Peel David, Pinder Rich, Purdie David M, Reynolds Peggy, Stram Dan, West Dee, Wright William E, Ziogas Argyrios, Ross Ronald K
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
J Natl Cancer Inst. 2005 Jun 1;97(11):805-12. doi: 10.1093/jnci/dji140.
Epidemiologic studies of the association between nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and breast cancer risk have yielded inconsistent results. We investigated the association of NSAID use with risk of breast cancer in the California Teachers Study cohort, with special attention to risk of specific breast cancer subtypes and to type of NSAID used.
We analyzed data on 114 460 women in the California Teachers Study cohort who were aged 22 to 85 years and free of breast cancer at baseline in 1995 to 1996. Information on frequency and duration of NSAID use was collected through a self-administered questionnaire. A total of 2391 women were diagnosed with breast cancer during the follow-up period from 1995 to 2001. We used Cox proportional hazards regression to estimate relative risks (RR) and 95% confidence intervals (CI) of breast cancer subtypes with NSAID use.
Neither regular use (more than once a week) of any NSAID (aspirin and ibuprofen combined) nor regular use of aspirin was associated with breast cancer risk (RR = 1.09, 95% CI = 0.97 to 1.21 for daily versus no regular use of NSAIDs and RR = 0.98, 95% CI = 0.86 to 1.13 for daily versus no regular use of aspirin). However, long-term (> or = 5 years) daily aspirin users had a non-statistically significant decreased risk of estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer (RR = 0.80, 95% CI = 0.62 to 1.03). In contrast, we observed a statistically significantly increased risk of ER/PR-negative breast cancer with long-term daily use of aspirin (RR = 1.81, 95% CI = 1.12 to 2.92). In this population, 11 fewer ER/PR-positive breast cancer cases and seven excess ER/PR-negative breast cancer cases may be due to daily long-term aspirin use among 2391 breast cancer cases observed over 6 years if the association were proven to be causal. Long-term daily use of ibuprofen was also associated with an increased risk of breast cancer (RR = 1.51, 95% CI = 1.17 to 1.95), particularly of nonlocalized tumors (RR = 1.92, 95% CI = 1.24 to 2.97). If causality were subsequently proven, 16 of the observed 2391 breast cancer cases and 8 of the 713 non-localized breast cancer cases would be attributable to long-term daily use of ibuprofen.
Long-term daily use of NSAIDs was not associated with breast cancer risk overall. Ibuprofen use was associated with an increased risk of breast cancer, and long-term daily aspirin use was associated with an increased risk of ER/PR-negative breast cancer. However, it is not clear if the observed association is causal.
关于阿司匹林和布洛芬等非甾体抗炎药（NSAIDs）与乳腺癌风险之间关联的流行病学研究结果并不一致。我们在加利福尼亚教师研究队列中调查了NSAIDs使用与乳腺癌风险的关联，特别关注特定乳腺癌亚型的风险以及所使用的NSAIDs类型。
我们分析了加利福尼亚教师研究队列中114460名年龄在22至85岁之间且在1995年至1996年基线时无乳腺癌的女性的数据。通过自行填写的问卷收集NSAIDs使用频率和持续时间的信息。在1995年至2001年的随访期间，共有2391名女性被诊断为乳腺癌。我们使用Cox比例风险回归来估计NSAIDs使用情况下乳腺癌亚型的相对风险（RR）和95%置信区间（CI）。
定期使用（每周超过一次）任何NSAIDs（阿司匹林和布洛芬合并）或定期使用阿司匹林均与乳腺癌风险无关（每日使用与不定期使用NSAIDs相比，RR = 1.09，95% CI = 0.97至1.21；每日使用与不定期使用阿司匹林相比，RR = 0.98，95% CI = 0.86至1.13）。然而，长期（≥5年）每日使用阿司匹林的使用者患雌激素受体和孕激素受体（ER/PR）阳性乳腺癌的风险有非统计学意义的降低（RR = 0.80，95% CI = 0.62至1.03）。相比之下，我们观察到长期每日使用阿司匹林会使ER/PR阴性乳腺癌的风险有统计学意义的增加（RR = 1.81，95% CI = 1.12至2.92）。在该人群中，如果这种关联被证明是因果关系，那么在6年期间观察到的2391例乳腺癌病例中，可能因长期每日使用阿司匹林而导致ER/PR阳性乳腺癌病例减少11例，ER/PR阴性乳腺癌病例增加7例。长期每日使用布洛芬也与乳腺癌风险增加有关（RR = 1.51，95% CI = 1.17至1.95），尤其是非局限性肿瘤（RR = 1.92，95% CI = 1.24至2.97）。如果随后证明存在因果关系，那么在观察到的2391例乳腺癌病例中，16例以及713例非局限性乳腺癌病例中的8例将归因于长期每日使用布洛芬。
总体而言，长期每日使用NSAIDs与乳腺癌风险无关。使用布洛芬与乳腺癌风险增加有关，长期每日使用阿司匹林与ER/PR阴性乳腺癌风险增加有关。然而，尚不清楚所观察到的关联是否为因果关系。
