Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Rd, Gainesville, FL, 32610, USA.
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA.
Breast Cancer Res Treat. 2020 Feb;180(1):1-19. doi: 10.1007/s10549-019-05516-1. Epub 2020 Jan 2.
Epidemiological evidence on the risk factors for uterine/endometrial cancer in breast cancer (BCa) survivors is limited and inconsistent. Therefore, we critically reviewed and summarized available evidence related to the risk factors for uterine/endometrial cancer in BCa survivors.
We conducted a literature search through PubMed, Web of Science Core Collection/Cited Reference Search, as well as through manual searches of the bibliographies of the articles identified in electronic searches. We included in this review studies that were published up to November 30, 2018 that were accessible in full-text format and were published in English.
Of the 27 eligible studies, 96% had > 700 participants, 74% were prospective cohorts, 70% originated outside of the US, 44% reported as having pre-/postmenopausal women, and 26% reported having racially heterogeneous populations. Risk factors positively associated with uterine/endometrial cancer risk among BCa survivors included age at BCa diagnosis > 50 years, African American race, greater BMI/weight gain, and Tamoxifen treatment. For other lifestyle, reproductive and clinical factors, associations were either not significant (parity) or inconsistent (HRT use, menopausal status, smoking status) or had limited evidence (alcohol intake, family history of cancer, age at first birth, oral contraceptive use, age at menopause, comorbidities).
We identified several methodological concerns and limitations across epidemiological studies on potential risk factors for uterine/endometrial cancer in BCa survivors, including lack of details on uterine/endometrial cancer case ascertainment, varying and imprecise definitions of important covariates, insufficient adjustment for potential confounders, and small numbers of uterine/endometrial cancer cases in the overall as well as stratified analyses. Based on the available evidence, older age and higher body weight measures appear to be a shared risk factor for uterine/endometrial cancer in the general population as well as in BCa survivors. In addition, there is suggestive evidence that African American BCa survivors have a higher risk of uterine/endometrial cancer as compared to their White counterparts. There is also evidence that Tamoxifen contributes to uterine/endometrial cancer in BCa survivors. Given limitations of existing studies, more thorough investigation of these associations is warranted to identify additional preventive strategies needed for BCa survivors to reduce uterine/endometrial cancer risk and improve overall survival.
乳腺癌（BCa）幸存者中与子宫/子宫内膜癌相关的风险因素的流行病学证据有限且不一致。因此，我们对与 BCa 幸存者中子宫/子宫内膜癌相关风险因素的现有证据进行了批判性回顾和总结。
我们通过 PubMed、Web of Science 核心合集/Cited Reference Search 以及对电子搜索中确定的文章的参考文献进行手动搜索进行了文献检索。我们将截至 2018 年 11 月 30 日发表的全文可获取的研究纳入本综述，这些研究发表于英语国家。
在 27 项符合条件的研究中，96%的研究纳入了>700 名参与者，74%为前瞻性队列研究，70%的研究来自美国以外，44%的研究报告了绝经前和绝经后女性，26%的研究报告了种族多样化人群。与 BCa 幸存者中子宫/子宫内膜癌风险相关的风险因素包括诊断 BCa 时年龄>50 岁、非裔美国人、更高的 BMI/体重增加和他莫昔芬治疗。对于其他生活方式、生殖和临床因素，相关性要么不显著（生育），要么不一致（HRT 使用、绝经状态、吸烟状态），要么证据有限（饮酒、癌症家族史、初产年龄、口服避孕药使用、绝经年龄、合并症）。
我们发现，在关于 BCa 幸存者中子宫/子宫内膜癌潜在风险因素的流行病学研究中，存在几个方法学问题和局限性，包括对子宫/子宫内膜癌病例确定的细节缺乏说明、重要协变量的定义存在差异且不精确、对潜在混杂因素的调整不足，以及整体和分层分析中子宫/子宫内膜癌病例数量较少。基于现有证据，年龄较大和体重较高似乎是一般人群以及 BCa 幸存者中子宫/子宫内膜癌的共同风险因素。此外，有证据表明，非裔美国 BCa 幸存者的子宫/子宫内膜癌风险高于其白人同行。还有证据表明，他莫昔芬会导致 BCa 幸存者发生子宫/子宫内膜癌。鉴于现有研究的局限性，需要更彻底地研究这些关联，以确定 BCa 幸存者需要采取哪些额外的预防策略来降低子宫/子宫内膜癌风险并改善总体生存。
