Rookus M A, van Leeuwen F E
Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Natl Cancer Inst. 1996 Dec 4;88(23):1759-64. doi: 10.1093/jnci/88.23.1759.
In general, no association has been found between spontaneous abortion (naturally occurring termination of a pregnancy) and the risk for breast cancer. With respect to induced abortion (termination of a pregnancy by artificial means), the results have been more inconclusive. A positive association was found in five studies, no association was found in six studies, and a negative association was found in the only cohort study. It is thought that part of the inconsistency of the reported results may be attributable to reporting (recall) bias, since all but two studies on induced abortion used the case-control design and were based only on information obtained from study subjects. In comparison with breast cancer case patients, healthy control subjects may be more reluctant to report on a controversial, emotionally charged subject such as induced abortion. Thus, differential underreporting may be a cause of spurious associations in case-control studies.
Our goal was threefold: 1) to evaluate the relationship between a history of induced or spontaneous abortion and the risk for breast cancer in a Dutch population-based, case-control study; 2) to examine reporting bias by comparing risks between two geographic areas (i.e., western regions and southeastern regions in The Netherlands that differ in prevalence of and attitudes toward induced abortion); and 3) to compare reporting bias in data on induced abortion with reporting bias in data on oral contraceptive use.
Data analyzed in this study were obtained from 918 women (20-54 years of age at diagnosis) who were diagnosed with invasive breast cancer during the period from 1986 through 1989 and had been initially enrolled in a population-based, case-control study investigating oral contraceptive use and breast cancer risk. The women resided in one of four geographic areas that were covered by Regional Cancer Registries: two western regions (Amsterdam and West) and two southeastern regions (East and Eindhoven). Each case patient was pair-matched, on the basis of age (within 1 year) and region, with a control subject who was randomly selected from municipal registries that fully covered the Dutch population. Both the case patients and the control subjects were interviewed at home by the same trained interviewer, who used a structured questionnaire. Reporting bias was examined indirectly by comparing risks between the western and the southeastern regions of the country, which differ in the prevalence of and attitude toward induced abortion. Multivariate conditional logistic regression methods for individually matched case-control studies were used to estimate relative risks (RRs). Reported P values are two-sided.
Among parous women, a history of induced abortion was associated with a 90% increased risk for breast cancer (adjusted RR = 1.9; 95% confidence interval [CI] = 1.1-3.2). Among nulliparous women, no association between induced abortion and breast cancer was found. Neither among parous women nor among nulliparous women was a history of spontaneous abortion related to the risk for breast cancer. The association between induced abortion and breast cancer was stronger in the southeastern regions of the country, which have a predominantly Roman Catholic population, than in the western regions (adjusted RR = 14.6 [95% CI = 1.8-120.0] versus adjusted RR = 1.3 [95% CI = 0.7-2.6], respectively; test of difference between regions, P = .017), suggesting reporting bias. Support for reporting bias as an explanation for the regional differences was also found in data supplied by both study subjects and their physicians on the use of oral contraceptives. In comparison with physicians, control subjects in the southeastern regions underreported the duration of their oral contraceptive use by 6.3 months more than control subjects in the western regions (P = .007)...
一般而言,自然流产(妊娠自然终止)与患乳腺癌风险之间未发现关联。关于人工流产(通过人工手段终止妊娠),结果更具不确定性。五项研究发现存在正相关,六项研究未发现关联,唯一的队列研究发现存在负相关。据认为,报告结果不一致的部分原因可能是报告(回忆)偏倚,因为除两项研究外,所有关于人工流产的研究均采用病例对照设计,且仅基于从研究对象处获得的信息。与乳腺癌病例患者相比,健康对照者可能更不愿报告诸如人工流产这类有争议且情绪化的话题。因此,差异漏报可能是病例对照研究中虚假关联的一个原因。
我们的目标有三个:1)在一项基于荷兰人群的病例对照研究中评估人工流产或自然流产史与患乳腺癌风险之间的关系;2)通过比较两个地理区域(即荷兰西部地区和东南部地区,这两个地区在人工流产的发生率和态度方面存在差异)的风险来检查报告偏倚;3)比较人工流产数据中的报告偏倚与口服避孕药使用数据中的报告偏倚。
本研究分析的数据来自918名女性(诊断时年龄在20 - 54岁之间),她们在1986年至1989年期间被诊断为浸润性乳腺癌,最初参加了一项基于人群的病例对照研究,该研究调查口服避孕药使用情况与乳腺癌风险。这些女性居住在区域癌症登记处覆盖的四个地理区域之一:两个西部地区(阿姆斯特丹和西部)和两个东南部地区(东部和埃因霍温)。根据年龄(相差1岁以内)和地区,为每位病例患者与一名从完全覆盖荷兰人口的市政登记处随机选取的对照者进行配对。病例患者和对照者均由同一名经过培训的访谈员在家中进行访谈,访谈员使用结构化问卷。通过比较该国西部地区和东南部地区的风险间接检查报告偏倚,这两个地区在人工流产的发生率和态度方面存在差异。使用个体匹配病例对照研究的多变量条件逻辑回归方法来估计相对风险(RRs)。报告的P值为双侧。
在经产妇中,人工流产史与患乳腺癌风险增加90%相关(调整后的RR = 1.9;95%置信区间[CI] = 1.1 - 3.2)。在未生育女性中,未发现人工流产与乳腺癌之间存在关联。在经产妇和未生育女性中,自然流产史均与患乳腺癌风险无关。在该国东南部地区(主要是罗马天主教人口),人工流产与乳腺癌之间的关联比西部地区更强(调整后的RR分别为14.6[95%CI = 1.8 - 120.0]和调整后的RR = 1.3[95%CI = 0.7 - 2.6];地区间差异检验,P = 0.017),这表明存在报告偏倚。在研究对象及其医生提供的关于口服避孕药使用的数据中也发现了支持将报告偏倚作为区域差异解释的证据。与医生相比,东南部地区的对照者报告的口服避孕药使用时长比西部地区的对照者少6.3个月(P = 0.007)……