某些抗精神病药可增加乳腺癌风险
精神分裂症女性患者与普通女性人群相比，乳腺癌发病率显著较高，可达25%。虽然精神分裂症女性患者的肥胖、糖尿病、吸烟等比例较高，生育和哺乳的比例较低，都是乳腺癌的风险因素，但是大多数抗精神病药可升高血清催乳素水平，对乳腺癌发病率的影响如何？
2021年8月30日，英国《柳叶刀》精神病学分册在线发表东芬兰大学纽瓦涅米医院、赫尔辛基大学、瑞典卡罗林学院、斯德哥尔摩市议会精神病学研究中心、加拿大渥太华大学、渥太华医院、意大利帕多瓦大学、美国纽约朱克医院、朱克医学院、德国柏林大学夏里特医学院的芬兰全国嵌套病例对照研究报告，调查分析了30785例精神分裂症女性服用抗精神病药对乳腺癌发病率的影响。
该研究利用芬兰全国医院治疗、处方药购买和癌症诊断登记数据库，将精神分裂症女性按年龄和疾病持续时间进行匹配，按1∶5的比例分为有乳腺癌的病例组与无乳腺癌的对照组。病例组和对照组的年龄范围为18～85岁，排除标准为过去被诊断出任何癌症、接受过器官移植或乳房切除术、感染过人类免疫缺陷病毒。通过条件逻辑回归模型对合并症和同时其他用药等影响因素进行校正后，分析服用抗精神病药（利培酮、奋乃静、硫利达嗪、奥氮平、左旋丙嗪、氯普噻吨、氯丙嗪、喹硫平、氟哌啶醇、氯氮平、珠氯噻醇）对乳腺癌发病率的影响。
结果，1972～2014年被诊断为精神分裂症的女性共计30785例，其中2000年1月1日～2017年12月31日被诊断出乳腺癌1069例。
病例组1069例与匹配对照组5339例相比，不同抗精神病药的乳腺癌发病率：
利培酮：32.50%比29.20%
奋乃静：31.80%比29.50%
硫利达嗪：26.80%比26.70%
奥氮平：24.70%比24.40%
左旋丙嗪：24.30%比23.80%
氯普噻吨：22.20%比20.40%
氯丙嗪：17.80%比14.30%
喹硫平：15.90%比16.10%
氟哌啶醇：13.60%比13.70%
氯氮平：13.20%比11.60%
珠氯噻醇：10.60%比11.30%
对于不升高催乳素的抗精神病药：
服用1～4年与<1年相比：乳腺癌发病率相似（校正后比值比：0.95，95%置信区间：0.73～1.25）
服用≥5年与<1年相比：乳腺癌发病率相似（校正后比值比：1.19，95%信置区间：0.90～1.58）
对于升高催乳素的抗精神病药：
服用1～4年与<1年相比：乳腺癌发病率相似（校正后比值比：1.04，95%置信区间：0.79～1.36）
服用≥5年与<1年相比：乳腺癌发病率高56%（校正后比值比：1.56，95%信置区间：1.27～1.92，P<0.001）
因此，该大样本长期随访研究结果表明，长期服用升高催乳素的抗精神病药，与短期服用或不升高催乳素的抗精神病药相比，精神分裂症女性的乳腺癌发病率显著较高。对于正在接受升高催乳素的抗精神病药治疗的精神分裂症女性，需要监测血清催乳素水平、解决高催乳素血症。
相关链接
Lancet Psychiatry. 2021 Aug 30. Online ahead of print.
Antipsychotic use and risk of breast cancer in women with schizophrenia: a nationwide nested case-control study in Finland.
Heidi Taipale, Marco Solmi, Markku Lahteenvuo, Antti Tanskanen, Christoph U Correll, Jari Tiihonen.
University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; University of Helsinki, Helsinki, Finland; Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; University of Ottawa, Ottawa, ON, Canada; The Ottawa Hospital, Ottawa, ON, Canada; University of Padua, Padua, Italy; Zucker Hillside Hospital, New York City, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Charité Universitatsmedizin, Berlin, Germany.
BACKGROUND: Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing antipsychotics contributes to increased odds of breast cancer.
METHODS: We used Finnish nationwide registers of hospital treatment, prescription drug purchases, and cancer diagnoses to do a nested case-control study. Of women with schizophrenia, those with breast cancer (cases) were matched by age and duration of illness with five women without cancer (controls). Cases and controls were aged 18-85 years and exclusion criteria were any previous cancer diagnoses, receipt of organ transplant, mastectomy, or diagnosis of HIV. The main analysis was the association between cumulative exposure to prolactin-increasing drugs and breast cancer. The analyses were done with conditional logistic regression, by adjusting for comorbid conditions and concomitant medications. Ethnicity data were not available.
FINDINGS: Of 30785 women diagnosed with schizophrenia between 1972 and 2014, 1069 were diagnosed with breast cancer between Jan 1, 2000, and Dec 31, 2017. Compared with 5339 matched controls, 1-4 years cumulative exposure (adjusted odds ratio [OR] 0.95, 95% CI 0.73-1.25) or 5 or more years exposure (adjusted OR 1.19, 0.90-1.58) to prolactin-sparing antipsychotics (including clozapine, quetiapine, or aripiprazole) was not associated with an increased risk of breast cancer in comparison with minimal exposure (<1 year). When compared with less than 1 year of exposure to prolactin-increasing antipsychotics (all other antipsychotics), 1-4 years of exposure was not associated with an increased risk, but exposure for 5 or more years was associated with an increased risk (adjusted OR 1.56 [1.27-1.92], p<0.001). The risk for developing lobular adenocarcinoma associated with long-term use of prolactin-increasing antipsychotics (adjusted OR 2.36 [95% CI 1.46-3.82]) was higher than that of developing ductal adenocarcinoma (adjusted OR 1.42 [95% CI 1.12-1.80]).
INTERPRETATION: Long-term exposure to prolactin-increasing, but not to prolactin-sparing, antipsychotics is significantly associated with increased odds of breast cancer. Monitoring prolactinemia and addressing hyperprolactinemia is paramount in women with schizophrenia being treated with prolactin-increasing antipsychotics.
FUNDING: Finnish Ministry of Social Affairs and Health
DOI: 10.1016/S2215-0366(21)00241-8