Gestational Hypertensive Disorders and Maternal Breast Cancer Risk in a Nationwide Cohort of 40,720 Parous Women

Abstract

Background: Preeclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35-74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported diagnoses of eclampsia, preeclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race-ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results:The prevalence of gestational hypertensive disease was 12%. During follow-up (mean = 10.9 years), 3,198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR = 1.0; 95% CI = 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a firstdegree family history of breast cancer.

Causal effects of hypertensive disorders of pregnancy on future gynecologic tumors: A two‐sample Mendelian randomization study

“…In the preceding decades, multiple studies have been carried out to explore the relationships between HDPs and gynecologic tumors, yielding inconsistent results due to variations in the study cohorts, research methodology, follow‐up duration, and adjustments for potential confounding variables. 11 , 12 , 13 , 36 , 37 A longitudinal study, featuring an average follow‐up duration of 19 years, conclude that HDPs did not constitute an independent risk for prevalent female cancers (ovarian, endometrial, and breast). 11 However, a nationwide cohort investigation with an average follow‐up period of 17.7 years discovered that a history of HDPs correlated with a diminished occurrence of breast cancer and an augmented incidence of endometrial cancer, but had no association with ovarian or cervical cancer.…”

“…However, when the analysis was stratified according to race and ethnicity, a positive association was suggested between HDPs and the risk of breast cancer among Hispanic/Latina women. 13 These varying findings might be attributed to underlying differences in various populations. Consequently, it is plausible that intrinsic genetic diversity among different study populations could lead to disparate outcomes.…”

“…In the preceding decades, multiple studies have been carried out to explore the relationships between HDPs and gynecologic tumors, yielding inconsistent results due to variations in the study cohorts, research methodology, follow‐up duration, and adjustments for potential confounding variables 11–13,36,37 . A longitudinal study, featuring an average follow‐up duration of 19 years, conclude that HDPs did not constitute an independent risk for prevalent female cancers (ovarian, endometrial, and breast) 11 .…”

“…9 By contrast, Goldberg et al defined women with any self-reported preeclampsia, eclampsia, or high blood pressure during pregnancy as those with a history of HDPs. 13 Unquestionably, determining the causal association between HDPs and future gynecologic tumors may have far-reaching influence on cancer prevention strategies. Given the potential for residual confounders, the infeasibility of randomized controlled trials (RCTs), and the scarcity of large cohort studies, innovative methodologies are urgently required to determine causality.…”

“…By contrast, Goldberg et al. defined women with any self‐reported preeclampsia, eclampsia, or high blood pressure during pregnancy as those with a history of HDPs 13 . Unquestionably, determining the causal association between HDPs and future gynecologic tumors may have far‐reaching influence on cancer prevention strategies.…”