Ultraviolet (UV) radiation exposure, the primary source of vitamin D for most people, may reduce breast cancer risk. To date, epidemiologic studies have shown inconsistent results. The Nurses' Health Study II is a U.S. nationwide prospective cohort of female registered nurses. A UV exposure model was linked with geocoded residential address histories. Early-life UV exposure was estimated based on the state of residence at birth, age 15, and age 30. Self-reported breast cancer was confirmed from medical records. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). From 1989 to 2013, 3,959 invasive breast cancer cases occurred among 112,447 participants. Higher UV exposure during adulthood was not associated with invasive breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.00, 95% CI: 0.90, 1.11, p for trend = 0.64) or according to estrogen receptor (ER) status. There were suggestive inverse associations between ER- breast cancer and early-life UV exposure at birth (adjusted HR = 0.94, 95% CI: 0.88, 1.01 per interquartile range increase [15.7 mW/m2]), age 15 (adjusted HR = 0.96, 95% CI: 0.89, 1.04 per 18.0 mW/m2), and age 30 (adjusted HR = 0.90, 95% CI: 0.82, 1.00 per 27.7 mW/m2). Ambient UV exposure during adulthood was not associated with risk of invasive breast cancer overall or by ER status. However, we observed suggestive inverse associations between early-life UV exposure and ER- breast cancer risk.

Ultraviolet (UV) radiation exposure, the primary source of vitamin D for most people, may reduce breast cancer risk. To date, epidemiologic studies have shown inconsistent results. The Nurses' Health Study II is a U.S. nationwide prospective cohort of female registered nurses. A UV exposure model was linked with geocoded residential address histories. Early-life UV exposure was estimated based on the state of residence at birth, age 15, and age 30. Self-reported breast cancer was confirmed from medical records. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). From 1989 to 2013, 3,959 invasive breast cancer cases occurred among 112,447 participants. Higher UV exposure during adulthood was not associated with invasive breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.00, 95% CI: 0.90, 1.11, p for trend = 0.64) or according to estrogen receptor (ER) status. There were suggestive inverse associations between ER- breast cancer and early-life UV exposure at birth (adjusted HR = 0.94, 95% CI: 0.88, 1.01 per interquartile range increase [15.7 mW/m2]), age 15 (adjusted HR = 0.96, 95% CI: 0.89, 1.04 per 18.0 mW/m2), and age 30 (adjusted HR = 0.90, 95% CI: 0.82, 1.00 per 27.7 mW/m2). Ambient UV exposure during adulthood was not associated with risk of invasive breast cancer overall or by ER status. However, we observed suggestive inverse associations between early-life UV exposure and ER- breast cancer risk.

Evidence of geographic disparities in breast cancer incidence within the U.S. and spatial analyses can provide insight into the potential contribution of environmental exposures or other geographically-varying factors to these disparities. We applied generalized additive models (GAMs) to smooth geocoded residential coordinates while adjusting for covariates. Our analysis included 3,478 breast cancer cases among 24,519 control women from the Nurses' Health Study II (NHSII). We first examined associations with residential location during adolescence (high school address) or early adulthood (address in 1991). We then assessed the contribution from known individual-level risk factors, measures of socioeconomic status (SES), and occupational and environmental factors that vary spatially and have been linked to breast cancer. Secondary analyses by estrogen receptor (ER) and menopausal status were also conducted. We identified geographic patterns of breast cancer risk associated with location during adolescence, with increased risk apparent in Michigan, the Northwest, and the New York City area, that shifted to southern New England when addresses during early adulthood were analyzed. Similar results were observed after adjustment for individual- and area-level factors, although spatial associations were no longer statistically significant. Breast cancer risk is not spatially uniform across the U.S. and incidence patterns varied depending on the timing during life of the residence considered. Geographic disparities persisted even after accounting for established and suspected breast cancer risk factors, suggesting that unmeasured environmental or lifestyle risk factors may explain geographic variation in risk in different parts of the country.

Background

Radon and its decay products, a source of ionizing radiation, are primarily inhaled and can deliver a radiation dose to breast tissue, where they may continue to decay and emit DNA damage-inducing particles. Few studies have examined the relationship between radon and breast cancer.

Methods

The Nurses' Health Study II (NHSII) includes U.S. female registered nurses who completed biennial questionnaires since 1989. Self-reported breast cancer was confirmed from medical records. County-level radon exposures were linked with geocoded residential addresses updated throughout follow-up. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

From 1989 to 2013, 3966 invasive breast cancer cases occurred among 112,639 participants. Increasing radon exposure was not associated with breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.06, 95% CI: 0.94, 1.21, p for trend = 0.30). However, women in the highest quintile of exposure (≥74.9 Bq/m³) had a suggested elevated risk of ER-/PR- breast cancer compared to women in the lowest quintile (<27.0 Bq/m³) (adjusted HR = 1.38, 95% CI: 0.97, 1.96, p for trend = 0.05). No association was observed for ER+/PR+ breast cancer.

Conclusions

Although we did not find an association between radon exposure and risk of overall or ER+/PR+ breast cancer, we observed a suggestive association with risk of ER-/PR- breast cancer.

Background

There is increasing concern that environmental exposures, such as air pollution, may be related to increasing rates of breast cancer; however, results from cohort studies have been mixed. We examined the association between particulate matter (PM) and measures of distance to roadway with the risk of incident breast cancer in the prospective nationwide Nurses' Health Study II (NHSII) cohort.

Methods

Incident invasive breast cancer from 1993 to 2011 (N = 3,416) was assessed among 115,921 women in the NHSII cohort. Time-varying Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (95% CI) for increases in ambient exposures to PM10, PM2.5-10, and PM2.5 and residential roadway proximity categories.

Results

In multivariable adjusted models, there was little evidence of an increased risk of breast cancer (or any of the receptor-specific subtypes) overall or by menopausal status with PM exposure. There was, however, a suggestion of increased risks among women living <50 m of the largest road type (HR = 1.60; 95% CI, 0.80-3.21) or within <50 m of the two largest road types (1.14; 95% CI, 0.84-1.54) compared with women living farther (≥200 m) away.

Conclusions

Among women in the NHSII, we found no statistically significant associations between particulate matter exposures and incidence of breast cancer overall, by menopausal status, or by hormone receptor subtype. There was, however, a suggestion that residential proximity to major roadways may be associated with increased risk.

Impact

These results suggest no elevated breast cancer risk with increasing exposures to particulate matter air pollution, but that other traffic-related exposures may be important. Cancer Epidemiol Biomarkers Prev; 25(8); 1274-6. ©2016 AACR.

Background

Findings from a recent prospective cohort study in California suggested increased risk of breast cancer associated with higher exposure to certain carcinogenic and estrogen-disrupting hazardous air pollutants (HAPs). However, to date, no nationwide studies have evaluated these possible associations. Our objective was to examine the impacts of mammary carcinogen and estrogen disrupting HAPs on risk of invasive breast cancer in a nationwide cohort.

Methods

We assigned HAPs from the US Environmental Protection Agency's 2002 National Air Toxics Assessment to 109,239 members of the nationwide, prospective Nurses' Health Study II (NHSII). Risk of overall invasive, estrogen receptor (ER)-positive (ER+), and ER-negative (ER-) breast cancer with increasing quartiles of exposure were assessed in time-varying multivariable proportional hazards models, adjusted for traditional breast cancer risk factors.

Results

A total of 3321 invasive cases occurred (2160 ER+, 558 ER-) during follow-up 1989-2011. Overall, there was no consistent pattern of elevated risk of the HAPs with risk of breast cancer. Suggestive elevations were only seen with increasing 1,2-dibromo-3-chloropropane exposures (multivariable adjusted HR of overall breast cancer = 1.12, 95% CI: 0.98-1.29; ER+ breast cancer HR = 1.09; 95% CI: 0.92, 1.30; ER- breast cancer HR = 1.14; 95% CI: 0.81, 1.61; each in the top exposure quartile compared to the lowest).

Conclusions

Exposures to HAPs during adulthood were not consistently associated with an increased risk of overall or estrogen-receptor subtypes of invasive breast cancer in this nationwide cohort of women.

Abstract Introduction Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models. Methods Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (<55, 55–64, and ≥65 years). Results MD was positively associated with risk of invasive tumors across all ages, with a two-fold increased risk for high (>51%) versus average density (11-25%). Women ages <55 years with high MD had stronger increased risk of ductal carcinoma in situ (DCIS) compared to women ages 55–64 and ≥65 years (P age-interaction = 0.02). Among all ages, MD had a stronger association with large (>2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (P age-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group. Conclusion MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women.

Background

Dioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed.

Objectives

To prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses' Health Study II (NHSII).

Methods

NHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

From 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status.

Discussion

Results from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.

Background

Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages <55 years. To provide insight into these associations, we examined the components of PMD [dense area (DA) and nondense area (NDA)] with breast cancer subtypes.

Methods

Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression.

Results

DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; P(trend) <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00 (Ref), 0.88, 0.72; P(trend) <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (P(trend) < 0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER(+) versus ER(-) tumors (P(het) = 0.02), while NDA was more strongly associated with decreased risk of ER(-) versus ER(+) tumors (P(het) = 0.03).

Conclusions

DA and NDA have differential associations with ER(+) versus ER(-) tumors that vary by age.

Impact

DA and NDA are important to consider when developing age- and subtype-specific risk models.

Background

Though mammographic density (MD) has been proposed as an intermediate marker of breast cancer risk, few studies have examined whether the associations between breast cancer risk factors and risk are mediated by MD, particularly by tumor characteristics.

Methods

Our study population included 3392 cases (1105 premenopausal) and 8882 (3192 premenopausal) controls from four case-control studies. For established risk factors, we estimated the percent of the total risk factor association with breast cancer that was mediated by percent MD (secondarily, by dense area and non-dense area) for invasive breast cancer as well as for subtypes defined by the estrogen receptor (ER+/ER-), progesterone receptor (PR+/PR-), and HER2 (HER2+/HER2-). Analyses were conducted separately in pre- and postmenopausal women.

Results

Positive associations between prior breast biopsy and risk of invasive breast cancer as well as all subtypes were partially mediated by percent MD in pre- and postmenopausal women (percent mediated = 11-27%, p ≤ 0.02). In postmenopausal women, nulliparity and hormone therapy use were positively associated with invasive, ER+ , PR+ , and HER2- breast cancer; percent MD partially mediated these associations (percent mediated ≥ 31%, p ≤ 0.02). Further, among postmenopausal women, percent MD partially mediated the positive association between later age at first birth and invasive as well as ER+ breast cancer (percent mediated = 16%, p ≤ 0.05).

Conclusion

Percent MD partially mediated the associations between breast biopsy, nulliparity, age at first birth, and hormone therapy with risk of breast cancer, particularly among postmenopausal women, suggesting that these risk factors at least partially influence breast cancer risk through changes in breast tissue composition.