抗抑郁药物可能影响早期乳腺癌女性生存

　　2016年11月14日，美国临床肿瘤学会官方期刊《临床肿瘤学杂志》在线发表丹麦癌症学会研究中心、哥本哈根大学医院、奥胡斯大学、欧登塞大学医院、南丹麦大学的全国队列登记研究报告，调查了原发早期乳腺癌之前治疗抑郁症的女性，所接受的治疗与不依从国家指南的风险是否增加、生存是否较差。

　　该研究于1998～2011年在丹麦确定了45325例被诊断为早期乳腺癌的女性，其中744例（2%）女性既往因抑郁症曾经前往医院就诊（住院或门诊）、6068例（13%）曾经抗抑郁药物治疗。通过多变量逻辑回归分析评估既往抑郁症治疗与未按指南进行乳腺癌治疗风险之间的相关性，通过多变量Cox回归分析比较总生存、乳腺癌相关生存，并比较乳腺癌之前曾经和未经抑郁症治疗的女性自杀死亡风险。

　　结果发现，在曾经抑郁症治疗的女性中，肿瘤分期与乳腺癌诊断延迟无关，但是乳腺癌之前给予抗抑郁药物的女性，接受非指南推荐治疗的风险显著增加14%（比值比：1.14；95%置信区间：1.03-1.27），总生存、乳腺癌相关生存风险分别显著增加21%、11%（风险比分别为：1.21、1.11，95%置信区间分别为：1.14～1.28、1.03～1.20）。既往因抑郁症曾经前往医院就诊的女性，估算风险也增加，但不显著。根据亚组分析，在未接受合理全身辅助疗法的女性中，抑郁症与生存较差的相关性特别强。

　　因此，作者认为既往曾经治疗抑郁症的女性占乳腺癌患者相当比例，存在接受非指南推荐乳腺癌治疗的风险，可能造成总生存和乳腺癌相关生存较差。作为临床医生，应对这类人群提供更多关注，并进行细致随访。有心理健康问题的女性，需要得到医疗决策帮助和卫生保健指导。

J Clin Oncol. 2016 Nov 14. [Epub ahead of print]

Survival After Early-Stage Breast Cancer of Women Previously Treated for Depression: A Nationwide Danish Cohort Study.

Nis P. Suppli, Christoffer Johansen, Lars V. Kessing, Anita Toender, Niels Kroman, Marianne Ewertz, Susanne O. Dalton.

Danish Cancer Society Research Center; Rigshospitalet, Copenhagen; Aarhus University, Aarhus; Odense University Hospital, University of Southern Denmark, Odense, Denmark.

PURPOSE: The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival.

MATERIAL AND METHODS: We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before breast cancer in multivariable Cox regression analyses.

RESULTS: Tumor stage did not indicate a delay in diagnosis of breast cancer in women previously treated for depression; however, those given antidepressants before breast cancer had a significantly increased risk of receiving nonguideline treatment (odds ratio, 1.14; 95% CI, 1.03 to 1.27) and significantly worse overall survival (hazard ratio, 1.21; 95% CI, 1.14 to 1.28) and breast cancer-specific survival (hazard ratio, 1.11; 95% CI, 1.03 to 1.20). Increased but nonsignificant estimated risks were also found for women with previous hospital contacts for depression. In subgroup analyses, the association of depression with poor survival was particularly strong among women who did not receive the indicated adjuvant systemic therapy.

CONCLUSION: Women previously treated for depression constitute a large subgroup of patients with breast cancer who are at risk for receiving nonguideline breast cancer treatment, which probably contributes to poorer overall and breast cancer-specific survival.

DOI: 10.1200/JCO.2016.68.8358