Therapeutic and Diagnostic Factors as Related to Cancer

这个项目的一个主要重点是确定外源性激素与随后的癌症风险的关系。我们最近的分析是使用乳腺癌检测示范项目参与者的后续研究数据来评估更年期激素与子宫内膜癌风险的关系。乳腺癌检测示范项目是一项全国性的大型乳房筛查项目。使用类似于以前对乳腺癌和卵巢癌风险的分析方法，我们发现风险与非对立雌激素的使用有很强的关系，正如许多其他研究人员所观察到的那样。尽管使用雌激素和孕激素联合治疗的患者风险较低，但与不使用雌激素和孕激素联合治疗的患者相比，风险升高仍有关联。因此，这些结果对长期使用联合替代疗法的安全性提出了质疑。 我们也对其他激素暴露的影响感兴趣，包括用于治疗不孕症的促排卵药物。还进行了一项回溯性队列研究，评估了不同不孕症原因和相关治疗对癌症风险的影响。这项研究包括对早在20世纪60年代的S确诊的患者的病历进行详细提取，并通过问卷调查获得最新的健康信息。这项研究的一个优势是收集了关于不孕不育原因的详细信息。分析表明，不孕症类型(原发与继发)是癌症风险的更重要的预测因素，而不是特定的不孕原因。然而，子宫内膜异位症患者患卵巢癌的风险特别高。总体而言，这项研究提供了关于使用促排卵药物的令人放心的结果，表明使用克罗米芬或人类绝经期促性腺激素没有显著增加癌症风险。然而，在跟踪时间最长的受试者(15年或20年以上)中，乳腺癌和卵巢癌的风险都略有增加，这支持了对这些药物的长期影响进行额外监测的必要性。 某些医疗设备也引起了人们的兴趣，包括硅胶乳房植入物的长期安全。鉴于乳房植入物可能会干扰病变的乳房X光摄影，对乳腺癌风险的影响一直令人担忧。然而，在我们进行的一项大型回顾研究中，我们没有发现乳腺癌风险发生变化的证据。这些患者通常也没有经历其他癌症部位的变化，尽管在肺癌和脑癌的风险中观察到了升高，其原因尚不清楚。在一项死亡率分析中，植入患者自杀死亡的风险显著增加，但其他死亡原因与普通人群相似。考虑到研究人群的老龄化性质，这项研究中的患者继续被跟踪观察未来的致命事件，这一点很重要。我们最近还评估了对各种结缔组织疾病的影响。总体而言，结果相当令人放心，尽管这项调查确实突显了评估相关性的复杂性，因为大多数个别疾病很罕见，而且诊断和报告存在各种困难。 最近的队列研究表明，有骨折史或骨密度低的女性患乳腺癌的风险降低。骨丢失的严重程度和时间对风险的影响尚未被调查，其他风险因素(家族史、人体测量因素、体力活动和外源性激素)改变与骨密度的关系的程度尚不清楚。为了详细说明这些研究问题，我们正在对20,000多名绝经后妇女进行跟踪研究，她们自愿参加骨增强药物阿仑磷酸钠的临床试验。

A major emphasis of this project has been to define the relationship of exogenous hormones to subsequent cancer risk. Our most recently analyses have related to assessing the relationships of menopausal hormones to endometrial cancer risk using data from the follow-up study of participants in the Breast Cancer Detections Demonstration Project, a large nation-wide breast screening project. Using approaches similar to previous analyses for breast and ovarian cancer risk, we found strong relationships of risk with unopposed estrogen use, as have been observed by many other investigators. Although risks were less elevated for users of combined estrogen-progestin therapy, they contined to be associated with elevations in risk as compared with non-use. These results therefore raise questions regarding the safety of long-term use of combined replacement therapy. We have also had an interest in effects of other hormonal exposures, including ovulation stimulating drugs used to treat infertility. A retrospective cohort study was also conducted which allowed an assessment of effects on cancer risk of different causes of infertility and associated therapies. This study involved detailed abstraction of medical records of patients diagnosed as long ago as the 1960's and administration of questionnaires to obtained updated health information. A strength of the study was the detailed information collected on causes of infertility. Analyses showed that type of infertility (primary vs. secondary) was a more important predictor of cancer risk than specific causes of infertility. However, patients with endometriosis were at an especially high risk of developing ovarian cancer. In general, the study provided reassuring results regarding use of ovulation-inducing agents, showing no major increases in cancer risk relating to use of either clomiphene citrate or human menopausal gonadotropins. There were, however, slight increases in risk of both breast and ovarian cancers among the subjects followed for the longest periods of time (15 or 20+ years), supporting the need for additional monitoring of long-term effects of these agents. Certain medical devices have also been of interest, including the long-term safetly of silicone breast implants. Effects on breast cancer risk has been of concern, given that breast implants can interfere with the mammographic visualization of lesions. However, in a large retrospective study that we conducted, we found no evidence for an alteration in breast cancer risk. These patients also generally did not experience alterations in other cancer sites, although elevations were observed in the risk of lung and brain cancers, the explanation for which remains unclear. In a mortality analysis, implant patients had signficantly elevated risks of death from suicide, but other causes of death were similar to the general population. The patients in this study are continuing to be followed for future mortal events, of importance given the aging nature of the study population. We also recently assessed effects on various connective tissue diseases. In general, the results were fairly reassuring, although this investigation did highlight the complexities of evaluating the associations, given the rarity of most individual diseases, and a variety of diagnostic and reporting difficulties. Recent cohort studies demonstrated reduced breast cancer risks among women with a history of fractures or low bone mineral density. The impact of the severity and timing of bone loss on risk has not yet been investigated, and the extent to which other risk factors (family history, anthropometric factors, physical activity, and exogenous hormones) modify the relationship with bone density is unknown. To elaborate on these research questions, we are conducting a follow-up study of over 20,000 postmenopausal women who volunteered for a clinical trial of the bone-enhancing drug alendronate.