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

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 first-degree family history of breast cancer.

Vitamin D concentrations and breast cancer incidence among Black/African American and non-Black Hispanic/Latina women.

BACKGROUND: Vitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non-Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups. METHODS: The vitamin D-breast cancer association was evaluated using a case-cohort sample of self-identified Black/African American and non-Black Hispanic/Latina women participating in the US-wide Sister Study cohort. Circulating 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography-tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non-Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a mean follow-up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61-1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29-0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68-1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow-up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)2 D nor the 24,25(OH)2 D to 25(OH)D ratio were independently associated with breast cancer risk. CONCLUSIONS: This prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non-Black Hispanic/Latina and Black/African American women. LAY SUMMARY: Vitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non-Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self-identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

Persistence of Risk for Type 2 Diabetes After Gestational Diabetes Mellitus.

OBJECTIVE: Gestational diabetes mellitus complicates ∼6% of pregnancies and strongly predicts subsequent type 2 diabetes. It has not been fully elucidated how risk depends on the number of affected pregnancies or how long the excess risk persists. RESEARCH DESIGN AND METHODS: We assessed reproductive histories in relation to risk of type 2 diabetes using a nationwide cohort of 50,884 women. Among participants who initially did not have diabetes, 3,370 were diagnosed with diabetes during 10 years of follow-up. We used Cox proportional hazards models that allowed risk to depend on age, cumulative number of pregnancies with gestational diabetes mellitus, and time since the most recent affected pregnancy, adjusting for BMI, educational level, and race/ethnicity. RESULTS: History of one or more pregnancies with gestational diabetes mellitus predicted elevated age-specific risk of type 2 diabetes, with a hazard ratio of 3.87 (95% CI 2.60-5.75) 6-15 years after an affected pregnancy. Risk increased steeply with multiple affected pregnancies. The age-specific associations attenuated over time after an affected pregnancy, with an estimated 24% reduction of the hazard ratio per decade. Risk remained elevated, however, for >35 years. CONCLUSIONS: Gestational diabetes mellitus predicted markedly increased rates of type 2 diabetes. Relative risk increased substantially with each additional affected pregnancy. The estimated hazard ratio declined with time after a pregnancy with gestational diabetes mellitus but remained elevated for >35 years. Women recalling a history of gestational diabetes mellitus should be screened regularly for type 2 diabetes, even late in life.

Vitamin D Supplement Use and Risk of Breast Cancer by Race-Ethnicity.

BACKGROUND: Vitamin D has anticarcinogenic properties, but a relationship between vitamin D supplement use and breast cancer is not established. Few studies have accounted for changes in supplement use over time or evaluated racial-ethnic differences. METHODS: The Sister Study is a prospective cohort of 50,884 women with 35-74 years of age who had a sister with breast cancer, but no breast cancer themselves at enrollment (2003-2009). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D supplement use and incident breast cancer (3,502 cases; median follow-up 10.5 years). RESULTS: Vitamin D supplement use was common, with 64% reporting ever use (at least once per month) in the year before enrollment. Considering supplement use over time, ever use of vitamin D supplements was not meaningfully associated with breast cancer (HR = 0.96, 95% CI = 0.88, 1.0), relative to never use. However, after adjusting for prior use, recent use of vitamin D supplements ≥1/month was inversely associated with breast cancer (HR = 0.88, 95% CI = 0.78, 1.0), relative to nonrecent use. The inverse association was stronger for ductal carcinoma in situ (HR = 0.67, 95% CI = 0.52, 0.87) than invasive breast cancer (HR = 0.94, 95% CI = 0.72, 1.1, p-for-heterogeneity = 0.02). Supplement use was less common among African American/Black (56%) and non-Black Hispanic/Latina (50%) women than non-Hispanic White women (66%), but there was limited evidence of racial-ethnic differences in HRs (p-for-heterogeneity = 0.16 for ever use, P = 0.55 for recent). CONCLUSIONS: Our findings are consistent with the hypothesis that recent vitamin D use is inversely associated with breast cancer risk.

Perinatal and postnatal exposures and risk of young-onset breast cancer.

BACKGROUND: Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor. METHODS: We addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother's preeclampsia in that pregnancy, mother's smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula. RESULTS: In conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07-2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824-4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08-7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05-4.92). CONCLUSION: These results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype.

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

A peripheral artery disease screening study in Puerto Rico.

UNLABELLED: Peripheral artery disease (PAD) of the lower extremities is frequently underdiagnosed and undertreated. The results of screening for PAD in adults attending outpatient clinics at different sites in Puerto Rico from 2007 to 2010 are presented. METHODS: A total of 33 outpatients screening clinics were conducted at different sites throughout the Island. Following the ACC/AHA Guideline recommendations, asymptomatic patients who qualified were screened for PAD using the ankle-brachial index (ABI). An ABI < 0.9 was considered positive for PAD. We estimated the prevalence of PAD in the study population and used logistic regression models to assess factors associated with a positive screening test for PAD. RESULTS: A total of 933 patients were screened for PAD. Out of the 933 patients, the ABI was < 0.9 in 390 (41.8%) of them. Bivariate analysis showed a significant difference in PAD screening results by gender (P = 0.004) and history of arterial hypertension (P = 0.004). Regarding clinical characteristics, leg edema 44.7% (P = 0.001), intermittent claudication 40.3% (P = 0.002), distal extremity coldness 29.0% (P = 0.012), and weak lower extremity pulses 67.5% (P < 0.001) were more prevalent on patients with an ABI < 0.9. In the multivariate analysis, male gender (OR = 1.92, 95% CI: 1.18, 3.11) and arterial hypertension (OR = 2.16, 95% CI: 1.28, 3.65) were significantly associated with PAD after adjusting for specific confounders. CONCLUSIONS: Arterial hypertension, cigarette smoking, diabetes mellitus, and dyslipidemia are known key factors in development of PAD. Practicing physicians must be aware of the importance of an early diagnosis of PAD, particularly in the asymptomatic patient, so as to institute preventive and management measures.