Lipid levels after childbirth and association with number of children: A population-based cohort study.

OBJECTIVE: Low parity women are at increased risk of cardiovascular mortality. Unfavourable lipid profiles have been found in one-child mothers years before they conceive. However, it remains unclear whether unfavourable lipid profiles are evident in these women also after their first birth. The aim was to estimate post-pregnancy lipid levels in one-child mothers compared to mothers with two or more children and to assess these lipid's associations with number of children. METHODS: We used data on 32 618 parous women (4 490 one-child mothers and 28 128 women with ≥2 children) examined after first childbirth as part of Cohort of Norway (1994-2003) with linked data on reproduction and number of children from the Medical Birth Registry of Norway (1967-2008). Odds ratios (ORs) with 95% confidence intervals (CIs) for one lifetime pregnancy (vs. ≥2 pregnancies) by lipid quintiles were obtained by logistic regression and adjusted for age at examination, year of first birth, body mass index, oral contraceptive use, smoking and educational level. RESULTS: Compared to women with the lowest quintiles, ORs for one lifetime pregnancy for the highest quintiles of LDL and total cholesterol were 1.30 (95%CI: 1.14-1.45) and 1.43 (95%CI: 1.27-1.61), respectively. Sensitivity analysis (women <40 years) showed no appreciable change in our results. In stratified analyses, estimates were slightly stronger in overweight/obese, physically inactive and women with self-perceived bad health. CONCLUSIONS: Mean lipid levels measured after childbirth in women with one child were significantly higher compared to mothers with two or more children and were associated with higher probability of having only one child. These findings corroborate an association between serum lipid levels and one lifetime pregnancy (as a feature of subfecundity), emphasizing that these particular women may be a specific predetermined risk group for cardiovascular related disease and death.

Women's prepregnancy lipid levels and number of children: a Norwegian prospective population-based cohort study.

OBJECTIVE: To study prepregnancy serum lipid levels and the association with the number of children. DESIGN: Prospective, population-based cohort. SETTING: Linked data from the Cohort of Norway and the Medical Birth Registry of Norway. PARTICIPANTS: 2645 women giving birth to their first child during 1994-2003 (488 one-child mothers and 2157 women with ≥2 births) and 1677 nulliparous women. MAIN OUTCOME MEASURES: ORs for no and one lifetime pregnancy (relative to ≥2 pregnancies) obtained by multinomial logistic regression, adjusted for age at examination, education, body mass index (BMI), smoking, time since last meal and oral contraceptive use. RESULTS: Assessed in quintiles, higher prepregnant triglyceride (TG) and TG to high-density lipoprotein (TG:HDL-c) ratio levels were associated with increased risk of one lifetime pregnancy compared with having ≥2 children. Compared with the highest quintile, women in the lowest quintile of HDL cholesterol levels had an increased risk of one lifetime pregnancy (OR 1.7, 95% CI 1.2 to 2.4), as were women with the highest low-density lipoprotein (LDL) cholesterol, TG and TG:HDL-c ratio quintiles (compared with the lowest) (OR 1.2, 95% CI 0.8 to 1.7; OR 2.2, 95% CI 1.5 to 3.2; and OR 2.2, 95% CI 1.5 to 3.2, respectively). Similar effects were found in women with BMI≥25 and the highest LDL and total cholesterol levels in risk of lifetime nulliparity. CONCLUSION: Women with unfavourable prepregnant lipid profile had higher risk of having no or only one child. These findings substantiate an association between prepregnant serum lipid levels and number of children. Previously observed associations between low parity and increased cardiovascular mortality may in part be due to pre-existing cardiovascular disease lipid risk factors.

Communicating with Daughters About Familial Risk of Breast Cancer: Individual, Family, and Provider Influences on Women's Knowledge of Cancer Risk.

INTRODUCTION: Women facing complex and uncertain situations such as cancer in their families may seek information from a variety of sources to gain knowledge about cancer risk and reduce uncertainty. We describe and assess the relative importance of information sources about familial breast cancer at the individual, family, and healthcare provider levels influencing women's reporting they had enough information to speak with daughters about breast cancer. This outcome we refer to as being informed about breast cancer. MATERIALS AND METHODS: Sister Study participants, a cohort of women with a family history of breast cancer, were surveyed on family cancer history, family communication, social support, and interactions with healthcare providers (n = 11,766). Adjusted percentages and 95% confidence intervals for being informed about breast cancer versus not being informed were computed for individual-, family-, and provider-level characteristics in three steps using multivariate logistic regression models. RESULTS: We found 65% of women reported being informed about breast cancer while 35% did not. Having a trusted person with whom to discuss cancer concerns, having a lower versus higher perceived risk of breast cancer, having undergone genetic counseling, and being satisfied with physician discussions about breast cancer in their families were predictors of being informed about breast cancer. CONCLUSIONS: Although acquiring objective risk information, such as through genetic counseling, may contribute to a basic level of understanding, communication with providers and within other trusted relationships appears to be an essential component in women's reporting they had all the information they need to talk with their daughters about breast cancer.

Season of Conception, Smoking, and Preeclampsia in Norway.

BACKGROUND: Preeclampsia (PE) is a dangerous and unpredictable pregnancy complication. A seasonal pattern of risk would suggest that there are potentially preventable environmental contributors, but prior analyses have not adjusted for confounding by PE risk factors that are associated with season of conception. METHODS: Seasonal effects were modeled and tested by representing each day of the year as an angle on a unit circle and using trigonometric functions of those angles in predictive models, using "harmonic analysis." We applied harmonic Cox regression to model confounder-adjusted effects of the estimated day of the year of conception on risk of PE for births from the Medical Birth Registry of Norway for deliveries between 1999 and 2009. We also examined effect measure modification by parity, latitude (region), fetal sex, and smoking. RESULTS: In adjusted models, PE risk was related to season, with higher risk in spring conceptions and lower risk in autumn conceptions, with a risk amplitude (maximum compared with minimum) of about 20%. The pattern replicated across subpopulations defined by parity, latitude (region), fetal sex, and smoking. CONCLUSIONS: These results suggest that there is a seasonal driver for PE, with effects that are not modified by parity, latitude, fetal sex, or smoking. https://doi.org/10.1289/EHP963.

Lifetime Alcohol Intake, Binge Drinking Behaviors, and Breast Cancer Risk.

The prevalence of binge drinking in the United States is rising. While alcohol is a risk factor for breast cancer, less is known about the impact of episodic heavy drinking. In 2003-2009, women aged 35-74 years who were free of breast cancer were enrolled in the Sister Study (n = 50,884). Residents of the United States or Puerto Rico who had a sister with breast cancer were eligible. Multivariable Cox regression was used to estimate adjusted hazard ratios and 95% confidence intervals for breast cancer. During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Increased breast cancer risk was observed for higher lifetime alcohol intake (for ≥230 drinks/year vs. <60 drinks/year, hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.15, 1.58). Relative to low-level drinkers (<60 drinks/year), hazard ratios were increased for ever binge drinking (HR = 1.29, 95% CI: 1.15, 1.45) or blacking out (HR = 1.39, 95% CI: 1.17, 1.64). Compared with low-level drinkers who never binged, moderate drinkers (60-229 drinks/year) who binged had a higher risk (HR = 1.25, 95% CI: 1.08, 1.44). There was evidence of effect modification between moderate lifetime drinking and binging (relative excess risk due to interaction = 0.33, 95% CI: 0.10, 0.57). Our findings support the established association between lifetime alcohol intake and breast cancer and provide evidence for an increased risk associated with heavy episodic drinking, especially among moderate lifetime drinkers.

Breast cancer and exposure to tobacco smoke during potential windows of susceptibility.

PURPOSE: An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life. METHODS: Sister study participants (n = 50,884) aged 35-74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk. RESULTS: During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00-1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01-1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR = 1.44, 95% CI 1.02-2.02; 1940-1949, HR = 1.28, 95% CI 1.01-1.62). CONCLUSION: In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort.

The Sister Study Cohort: Baseline Methods and Participant Characteristics.

BACKGROUND: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. OBJECTIVE: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. METHODS: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. RESULTS: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2 (70%). Few (5%) reported any cancer prior to enrollment. CONCLUSIONS: The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.

Maternal Smoking Status in Successive Pregnancies and Risk of Having a Small for Gestational Age Infant.

BACKGROUND: Smoking during pregnancy is linked to having a small for gestational age (SGA) baby. We estimated SGA risk among women who smoked persistently, quit smoking or started smoking during their first two pregnancies. METHODS: Data from the population-based Medical Birth Registry of Norway was used to evaluate self-reported smoking at the beginning and end of two successive pregnancies among 118 355 Nordic women giving birth 1999-2014. Relative risks (RR) with 95% confidence intervals (CI) of SGA in the second pregnancy were estimated using adjusted generalised linear models with non-smokers during both pregnancies serving as referent category. RESULTS: Daily smokers throughout both pregnancies had almost threefold increased SGA risk in the second pregnancy (RR 2.9, 95% CI 2.7, 3.1). Daily smokers in the first pregnancy, who abstained in the second, had a 1.3-fold increased risk (95% CI 1.1, 1.5). Intermediate risks were found among persistent daily smokers who quit by the end of the second pregnancy (RR 2.0, 95% CI 1.6, 2.4) and non-smokers in first pregnancy who smoked daily throughout their second (RR 1.8, 95% CI 1.4, 2.3). Persistently smoking women without SGA in first pregnancy, had a 2.7-fold increased risk of SGA in second pregnancy (95% CI 2.5, 3.0). CONCLUSIONS: Smoking throughout two successive pregnancies was associated with the greatest increased SGA risk compared with non-smokers, while cessation before or during the second pregnancy reduced this risk. Women who smoked in the first pregnancy without experiencing SGA are not protected against SGA in second pregnancy if they continue smoking.

Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large International Population-Based Study.

Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic.

High use of complementary and alternative medicine among a large cohort of women with a family history of breast cancer: the Sister Study.

Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had ≥1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast caner, research on the effectiveness of CAM use for disease prevention is needed.

Migraine and possible etiologic heterogeneity for hormone-receptor-negative breast cancer.

Migraine headache is often timed with the menstrual cycle. Some studies have reported reduced risk of breast cancer in migraineurs but most of those did not distinguish menstrually-related from non-menstrually-related migraine. To examine the possible associations between breast cancer and migraine overall and between cancer subcategories and the two migraine subtypes, we used a cohort study of 50,884 women whose sister had breast cancer and a sister-matched case-control study including 1,418 young-onset (<50 years) breast cancer cases. We analyzed the two studies individually and also in tandem via a hybrid Cox model, examining subcategories of breast cancer in relation to menstrually-related and non-menstrually-related migraine. History of migraine was not associated with breast cancer overall. Migraine showed an inverse association with ductal carcinoma in situ (HR = 0.77; 95% CI (0.62,0.96)). Also, women with non-menstrually-related migraine had increased risk (HR = 1.30, 95% CI (0.93,1.81)) while women with menstrually-related migraine had decreased risk (HR = 0.63, 95% CI (0.42,0.96)) of hormone-receptor-negative (ER-/PR-) cancer, with a significant contrast in estimated effects (P = 0.005). While replication of these subset-based findings will be needed, effect specificity could suggest that while migraine has little overall association with breast cancer, menstrual migraine may be associated with reduced risk of ER-/PR- breast cancer.

Breast Cancer Risk in Relation to Ambient Air Pollution Exposure at Residences in the Sister Study Cohort.

BACKGROUND: Some but not all past studies reported associations between components of air pollution and breast cancer, namely fine particulate matter ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2). It is yet unclear whether risks differ according to estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: This analysis includes 47,591 women from the Sister Study cohort enrolled from August 2003 to July 2009, in whom 1,749 invasive breast cancer cases arose from enrollment to January 2013. Using Cox proportional hazards and polytomous logistic regression, we estimated breast cancer risk associated with residential exposure to NO2, PM2.5, and PM10. RESULTS: Although breast cancer risk overall was not associated with PM2.5 [HR = 1.03; 95% confidence intervals (CI), 0.96-1.11], PM10 (HR = 0.99; 95% CI, 0.98-1.00), or NO2 (HR = 1.02; 95% CI, 0.97-1.07), the association with NO2 differed according to ER/PR subtype (P = 0.04). For an interquartile range (IQR) difference of 5.8 parts per billion (ppb) in NO2, the relative risk (RR) of ER(+)/PR(+) breast cancer was 1.10 (95% CI, 1.02-1.19), while there was no evidence of association with ER(-)/PR(-) (RR = 0.92; 95% CI, 0.77-1.09; Pinteraction = 0.04). CONCLUSIONS: Within the Sister Study cohort, we found no significant associations between air pollution and breast cancer risk overall. But we observed an increased risk of ER(+)/PR(+) breast cancer associated with NO2. IMPACT: Though these results suggest there is no substantial increased risk for breast cancer overall in relation to air pollution, NO2, a marker of traffic-related air pollution, may differentially affect ER(+)/PR(+) breast cancer.

Risk factors for young-onset invasive and in situ breast cancer.

PURPOSE: Young-onset breast cancers tend to be more aggressive than later-onset tumors and may have different risk factor profiles. Among young-onset cases, there may also be etiologic differences between ductal carcinomas in situ (DCIS) and invasive breast cancer, particularly if some factors promote malignant transformation. METHODS: We evaluated the association between several potential risk factors and young-onset breast cancer in the Two Sister Study (2008-2010), a sister-matched case-control study involving 1,406 women diagnosed with breast cancer before age 50 (1,185 invasive, 221 DCIS) and 1,648 controls. RESULTS: Older age at menarche, younger age at menopause, premenopausal hysterectomy, early age at first-term pregnancy, obesity, and consumption of alcohol were associated with reduced risk of young-onset breast cancer. These patterns remained when we limited analysis to invasive breast cancers. In general, effect estimates were similar for young-onset invasive breast cancer and DCIS, although the number of DCIS cases was small. CONCLUSIONS: In this sister-matched case-control study of young-onset breast cancer, many of the studied risk factors were associated with young-onset invasive breast cancer. There were few discernable differences in risk factors for young-onset DCIS versus young-onset invasive breast cancer.

Season and preterm birth in Norway: A cautionary tale.

BACKGROUND: Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. METHODS: We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2,321,652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. RESULTS: Naïve analysis of preterm rates across days of birth shows compelling evidence for seasonality (P < 10(-152)). However, the reconstructed numbers of conceptions also vary with season (P < 10(-307)), confounding results by inducing seasonal variation in the age distribution of the fetal population at risk. When we instead properly treat fetuses as the individuals at risk, restrict analysis to pregnancies with relatively accurate ultrasound-based assessment of gestational age (available since 1998) and adjust for socio-demographic factors and maternal smoking, we find modest effects of both time of year of conception and time of year at risk, with peaks for early preterm near early January and early July. CONCLUSIONS: Analyses of seasonal effects on preterm birth are demonstrably vulnerable to confounding by seasonality of conception, measurement error in conception dating, and socio-demographic factors. The seasonal variation based on fetuses reveals two peaks for early preterm, coinciding with New Year's Day and the early July beginning of Norway's summer break, and may simply reflect a holiday-related pattern of unintended conception.

In utero exposure to diethylstilbestrol and blood DNA methylation in women ages 40-59 years from the sister study.

In utero exposure to diethylstilbestrol (DES) has been associated with increased risk of adverse health outcomes such as fertility problems and vaginal as well as breast cancer. Animal studies have linked prenatal DES exposure to lasting DNA methylation changes. We investigated genome-wide DNA methylation and in utero DES exposure in a sample of non-Hispanic white women aged 40-59 years from the Sister Study, a large United States cohort study of women with a family history of breast cancer. Using questionnaire information from women and their mothers, we selected 100 women whose mothers reported taking DES while pregnant and 100 control women whose mothers had not taken DES. DNA methylation in blood was measured at 485,577 CpG sites using the Illumina HumanMethylation450 BeadChip. Associations between CpG methylation and DES exposure status were analyzed using robust linear regression with adjustment for blood cell composition and multiple comparisons. Although four CpGs had p<105, after accounting for multiple comparisons using the false discovery rate (FDR), none reached genome-wide significance. In conclusion, adult women exposed to DES in utero had no evidence of large persistent changes in blood DNA methylation.

Long-Term Air Pollution Exposure and Blood Pressure in the Sister Study.

BACKGROUND: Exposure to air pollution has been consistently associated with cardiovascular morbidity and mortality, but mechanisms remain uncertain. Associations with blood pressure (BP) may help to explain the cardiovascular effects of air pollution. OBJECTIVE: We examined the cross-sectional relationship between long-term (annual average) residential air pollution exposure and BP in the National Institute of Environmental Health Sciences' Sister Study, a large U.S. cohort study investigating risk factors for breast cancer and other outcomes. METHODS: This analysis included 43,629 women 35-76 years of age, enrolled 2003-2009, who had a sister with breast cancer. Geographic information systems contributed to satellite-based nitrogen dioxide (NO2) and fine particulate matter (≤ 2.5 µm; PM2.5) predictions at participant residences at study entry. Generalized additive models were used to examine the relationship between pollutants and measured BP at study entry, adjusting for cardiovascular disease risk factors and including thin plate splines for potential spatial confounding. RESULTS: A 10-µg/m(3) increase in PM2.5 was associated with 1.4-mmHg higher systolic BP (95% CI: 0.6, 2.3; p < 0.001), 1.0-mmHg higher pulse pressure (95% CI: 0.4, 1.7; p = 0.001), 0.8-mmHg higher mean arterial pressure (95% CI: 0.2, 1.4; p = 0.01), and no significant association with diastolic BP. A 10-ppb increase in NO2 was associated with a 0.4-mmHg (95% CI: 0.2, 0.6; p < 0.001) higher pulse pressure. CONCLUSIONS: Long-term PM2.5 and NO2 exposures were associated with higher blood pressure. On a population scale, such air pollution-related increases in blood pressure could, in part, account for the increases in cardiovascular disease morbidity and mortality seen in prior studies.

Hormone therapy and young-onset breast cancer.

Estrogen plus progestin hormone therapy (HT) is associated with an increased risk of postmenopausal breast cancer, but few studies have examined the impact of HT use on the risk of breast cancer in younger women. We assessed the association between estrogen plus progestin HT or unopposed estrogen HT and young-onset breast cancer using data from the Two Sister Study (2008-2010), a sister-matched study of 1,419 cases diagnosed with breast cancer before the age of 50 years and 1,665 controls. We assessed exposures up to a family-specific index age to ensure comparable opportunities for exposures and used propensity scores to control for birth cohort effects on HT use. Ever HT use was uncommon (7% and 11% in cases and controls, respectively). Use of estrogen plus progestin was not associated with an increased risk of young-onset breast cancer (odds ratio = 0.80, 95% confidence interval: 0.41, 1.59). Unopposed estrogen use was inversely associated with the risk of young-onset breast cancer (odds ratio = 0.58, 95% confidence interval: 0.34, 0.99). Duration of use, age at first use, and recency of use did not modify these associations.

Risk-benefit profiles of women using tamoxifen for chemoprevention.

BACKGROUND: Tamoxifen has been US Food and Drug Administration-approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer. METHODS: This research was conducted within The Sister Study, a cohort of 50884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009. Eligible women were breast cancer-free at enrollment and had a sister who had been diagnosed with breast cancer. Participants reported tamoxifen use, ages started and stopped taking tamoxifen, and total duration of use at enrollment. We identified 788 tamoxifen users and 3131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer). Characteristics associated with tamoxifen initiation were evaluated with multivariable conditional logistic regression. All statistical tests were two-sided. RESULTS: Based on published risk-benefit indices, 20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects. After 4.5 years, 46% of women had discontinued tamoxifen. CONCLUSIONS: While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.

Ambient air pollution exposure and incident adult asthma in a nationwide cohort of U.S. women.

RATIONALE: Limited prior data suggest an association between traffic-related air pollution and incident asthma in adults. No published studies assess the effect of long-term exposures to particulate matter less than 2.5 µm in diameter (PM2.5) on adult incident asthma. OBJECTIVES: To estimate the association between ambient air pollution exposures (PM2.5 and nitrogen dioxide, NO2) and development of asthma and incident respiratory symptoms. METHODS: The Sister Study is a U.S. cohort study of risk factors for breast cancer and other health outcomes (n = 50,884) in sisters of women with breast cancer (enrollment, 2003-2009). Annual average (2006) ambient PM2.5 and NO2 concentrations were estimated at participants' addresses, using a national land-use/kriging model incorporating roadway information. Outcomes at follow-up (2008-2012) included incident self-reported wheeze, chronic cough, and doctor-diagnosed asthma in women without baseline symptoms. MEASUREMENTS AND MAIN RESULTS: Adjusted analyses included 254 incident cases of asthma, 1,023 of wheeze, and 1,559 of chronic cough. For an interquartile range (IQR) difference (3.6 µg/m(3)) in estimated PM2.5 exposure, the adjusted odds ratio (aOR) was 1.20 (95% confidence interval [CI] = 0.99-1.46, P = 0.063) for incident asthma and 1.14 (95% CI = 1.04-1.26, P = 0.008) for incident wheeze. For NO2, there was evidence for an association with incident wheeze (aOR = 1.08, 95% CI = 1.00-1.17, P = 0.048 per IQR of 5.8 ppb). Neither pollutant was significantly associated with incident cough (PM2.5: aOR = 0.95, 95% CI = 0.88-1.03, P = 0.194; NO2: aOR = 1.00, 95% CI = 0.93-1.07, P = 0.939). CONCLUSIONS: Results suggest that PM2.5 exposure increases the risk of developing asthma and that PM2.5 and NO2 increase the risk of developing wheeze, the cardinal symptom of asthma, in adult women.