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邻苯二甲酸酯类是品种最多、产量最大、使用最广泛的塑化剂，可以增强塑料的弹性、透明度、耐用性和使用寿命，被用于多种产品，例如药丸、胶囊、黏度剂、胶凝剂、助膜剂、稳定剂、分散剂、润滑剂、黏结剂、乳化剂、悬浮剂等，其应用领域涵盖电子、农业、建筑、化妆品、个人护理产品、医疗器械、洗涤剂、表面活性剂、包装、儿童玩具、胶水、雕塑、蜡、油漆、油墨、涂料、制药、食品、纺织、印刷等。某些邻苯二甲酸酯类与雌二醇相似，可能促进乳腺癌的发生。现有关于该问题的流行病学研究较少，大多非前瞻性，并且结果不一。 2019年4月17日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表佛蒙特大学、埃默里大学、哈佛大学医学院布莱根妇女医院、哈佛大学陈曾熙公共卫生学院、南丹麦大学、南丹麦大学欧登塞医院、奥胡斯大学兰德斯医院的丹麦全国队列纵向研究报告，根据含有邻苯二甲酸酯类的包装药品处方回收，调查了邻苯二甲酸酯类暴露量与乳腺癌风险的相关性。 该丹麦全国队列研究于2005年1月1日～2015年12月31日对112万2042例无癌症病史且1995年1月1日～2005年1月1日无含邻苯二甲酸酯类药品接触史的丹麦女性居民进行随访。通过丹麦药品管理局内部数据库，确定丹麦市场销售药品的邻苯二甲酸酯类含量。将药品成分数据与丹麦全国处方登记数据进行关联，通过回收处方分析每年累计邻苯二甲酸酯类暴露量。随后，根据肿瘤雌激素受体状态，通过多因素比例风险回归模型，推算邻苯二甲酸酯类暴露量与新发乳腺浸润癌的相关性。 结果，经过中位10年随访，新发乳腺癌2万7111例，其中雌激素受体阳性占84%。大多数邻苯二甲酸酯类的暴露量与乳腺癌发病无关。不过，邻苯二甲酸二丁酯累计暴露量≥1万毫克与＜1万毫克相比，雌激素受体阳性乳腺癌发病率高约2倍（风险比：1.9，95%置信区间：1.1～3.5），符合该化合物的雌激素作用体外证据。较低水平的邻苯二甲酸二丁酯暴露量与乳腺癌发病率无关。 因此，该研究结果表明，女性应该避免接触大量邻苯二甲酸二丁酯，例如长期使用含邻苯二甲酸二丁酯成分的药品。 J Clin Oncol. 2019 Apr 17. [Epub ahead of print] Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study. Ahern TP, Broe A, Lash TL, Cronin-Fenton DP, Ulrichsen SP, Christiansen PM, Cole BF, Tamimi RM, Sorensen HT, Damkier P. University of Vermont, Burlington, VT; University of Southern Denmark, Odense, Denmark; Odense University Hospital, Odense, Denmark; Emory University, Atlanta, GA; Aarhus University Hospital/Randers Regional Hospital, Aarhus, Denmark; Brigham and Women's Hospital, Boston, MA; Harvard T.H. Chan School of Public Health, Boston, MA. PURPOSE: Phthalate exposure is ubiquitous and especially high among users of drug products formulated with phthalates. Some phthalates mimic estradiol and may promote breast cancer. Existing epidemiologic studies on this topic are small, mostly not prospective, and have given inconsistent results. We estimated associations between longitudinal phthalate exposures and breast cancer risk in a Danish nationwide cohort, using redeemed prescriptions for phthalate-containing drug products to measure exposure. METHODS: We ascertained the phthalate content of drugs marketed in Denmark using an internal Danish Medicines Agency ingredient database. We enrolled a Danish nationwide cohort of 1.12 million women at risk for a first cancer diagnosis on January 1, 2005. By combining drug ingredient data with the Danish National Prescription registry, we characterized annual, cumulative phthalate exposure through redeemed prescriptions. We then fit multivariable Cox regression models to estimate associations between phthalate exposures and incident invasive breast carcinoma according to tumor estrogen receptor status. RESULTS: Over 9.99 million woman-years of follow-up, most phthalate exposures were not associated with breast cancer incidence. High-level dibutyl phthalate exposure (≥ 10,000 cumulative mg) was associated with an approximately two-fold increase in the rate of estrogen receptor-positive breast cancer (hazard ratio, 1.9; 95% CI, 1.1 to 3.5), consistent with in vitro evidence for an estrogenic effect of this compound. Lower levels of dibutyl phthalate exposure were not associated with breast cancer incidence. CONCLUSION: Our results suggest that women should avoid high-level exposure to dibutyl phthalate, such as through long-term treatment with pharmaceuticals formulated with dibutyl phthalate. PMID: 30995175 DOI: 10.1200/JCO.18.02202
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