Search

PURPOSE: We investigated the associations of aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) with mammographic breast density (MBD) and their interactions in relation to breast cancer risk. METHODS: This study included 3,675 cancer-free women within the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) cohorts. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Information on medication use was collected in 1980 (NHS) and 1989 (NHSII) and updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users from all bi-annual questionnaires preceding the mammogram date. We used generalized linear regression to quantify associations of medications with MBD. Two-way interactions were examined in logistic regression models. RESULTS: In multivariate analysis, none of the anti-inflammatory medications were associated with PD, DA and NDA. We found no interactions of any of the medications with PD with respect to breast cancer risk (all p-interactions>0.05). However, some of the aspirin variables appeared to have positive associations with breast cancer risk limited only to women with PD 10–24% (past aspirin OR=1.56, 95% CI 1.03–2.35; current aspirin with

An important premise of epidemiology is that individuals with the same disease share similar underlying etiologies and clinical outcomes. In the past few decades, our knowledge of disease pathogenesis has improved, and disease classification systems have evolved to the point where no complex disease processes are considered homogenous. As a result, pathology and epidemiology have been integrated into the single, unified field of molecular pathological epidemiology (MPE). Advancing integrative molecular and population-level health sciences and addressing the unique research challenges specific to the field of MPE necessitates assembling experts in diverse fields, including epidemiology, pathology, biostatistics, computational biology, bioinformatics, genomics, immunology, and nutritional and environmental sciences. Integrating these seemingly divergent fields can lead to a greater understanding of pathogenic processes. The International MPE Meeting Series fosters discussion that addresses the specific research questions and challenges in this emerging field. The purpose of the meeting series is to: discuss novel methods to integrate pathology and epidemiology; discuss studies that provide pathogenic insights into population impact; and, educate next-generation scientists. Herein, we share the proceedings of the Fourth International MPE Meeting, held in Boston, MA, USA on May 30(th) to June 1(st), 2018. Major themes of this meeting included ‘integrated genetic and molecular pathologic epidemiology’, ‘immunology-MPE’, and ‘novel disease phenotyping’. The key priority areas for future research identified by meeting attendees included integration of tumor immunology and cancer disparities into epidemiologic studies, further collaboration between computational and population-level scientists to gain new insight on exposure-disease associations, and future pooling projects of studies with comparable data.

PURPOSE: We investigated the association of alcohol intake with mammographic breast density in postmenopausal women by their hormone therapy (HT) status. METHODS: This study included 2,100 cancer-free postmenopausal women within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percent breast density (PD), absolute dense (DA) and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square-root transformed. Alcohol consumption was assessed with a food frequency questionnaire (0

To conduct the first epidemiologic study prospectively examining the association between particulate matter air pollution

PURPOSE: To understand trends in the incidence and mortality of two human papillomavirus (HPV)-associated cancers, cervical and oropharyngeal cancer, in Massachusetts. METHODS: From 2004–2014, the Massachusetts Cancer Registry recorded 3,996 incident cases of oropharyngeal cancer and 2,193 incident cases of cervical cancer. Mortality data were obtained from the Massachusetts Registry of Vital Records and Statistics from 2008–2014. Rates were age-standardized to the 2000 US population and trends were assessed using joinpoint regression. RESULTS: While the incidence rate of cervical cancer (5.46 per 100,000) decreased by 2.41% annually (p=0.004), the incidence rate of oropharyngeal cancer among males (7.85 per 100,000) increased by 2.82% annually (p=0.0002). Mortality rates for both cancers decreased from 2008–2014 but were not statistically significant (Cervical −3.73% annually, p=0.29; Oropharyngeal −1.94% annually, p=0.44). CONCLUSION: The rising incidence rate of oropharyngeal cancer in men and the decreasing, but relatively high, incidence rate of cervical cancer in women highlight the need for further screening and prevention by HPV vaccination in Massachusetts.

Endometriosis and mammographic density have been hypothesized to be influenced by sex steroid hormonal exposures in adolescence and early adulthood. We investigated the association between endometriosis and mammographic density, a consistent and independent risk factor for breast cancer. We conducted a cross-sectional analysis among 1,581 pre- and postmenopausal women not previously diagnosed with breast cancer in the Nurses’ Health Study II cohort. We measured average percent mammographic density and absolute dense and non-dense breast area using a validated computer-assisted method. Multivariable linear regression was used to estimate the association between endometriosis and mammographic density among pre- and postmenopausal women separately. Among premenopausal women, average percent mammographic density was 43.1 % among women with endometriosis (n = 91) and 40.5 % among women without endometriosis (n = 1,150). Endometriosis was not associated significantly with mammographic density among premenopausal (% difference = 2.00 percentage points 95 % CI −1.33, 5.33) or among postmenopausal women (% difference = −0.89 percentage points 95 % CI −5.10, 3.33). Among premenopausal women, there was heterogeneity by BMI at age 18 (p value = 0.003), with a suggested association among those who were lean at age 18 (BMI

Vitamin D may reduce cell proliferation and tumor growth in breast tissue, and exposure may be most important during adolescence when breast tissue is developing. In the Nurses’ Health Study II, higher recalled adolescent vitamin D intake was associated with a lower risk of benign breast disease (BBD). Our study aimed to assess adolescent vitamin D exposure in relation to BBD in young women. Vitamin D was assessed in 6,593 adolescent girls (9–15 years of age at baseline) in the prospective Growing Up Today Study cohort using the mean energy-adjusted intakes from food frequency questionnaires in 1996, 1997, and 1998. In 1999, 5,286 girls reported skin color, sunscreen use, tanning bed use, and number of sunburns in the past year, and we used state of residence to assess low versus high ultraviolet index. Biopsy-confirmed BBD was reported on questionnaires in 2005, 2007, and 2010 (n = 122). Dietary vitamin D, tanning behaviors, and other sun exposure variables were not significantly associated with BBD in logistic regression models adjusted for age, family history of breast cancer or BBD, age at menarche, nulliparity, alcohol intake, body mass index, and physical activity. The relative risk for the top (>467 IU/day) versus bottom (

Matrix metalloproteinases (MMPs), in particular MMP1, 3, and 7, are believed to be critical to breast cancer invasion and metastasis and also may have important functions earlier in breast carcinogenesis. However, the relationship between circulating levels of MMP1, 3, and 7 and breast cancer risk is uncertain.We examined associations between plasma MMP1, 3, and 7 and breast cancer risk in a prospective case-control study nested within the Nurses' Health Study. Blood samples were collected from 801 cases who developed breast cancer between 1992 and 2000 and 801 matched controls, and MMP levels were measured via immunofluorescence assay.No overall association was observed between any of these MMPs and breast cancer risk [top vs. bottom quintile; MMP1: odds ratio (OR) 0.9; 95 % confidence interval (CI) 0.7, 1.3; p-trend = 0.51; MMP3: OR 1.1; 95 % CI 0.8, 1.5; p-trend = 0.88; MMP7: OR = 1.2; 95 % CI 0.8, 1.7; p-trend = 0.18]. Further, findings did not significantly vary by time since blood draw, body mass index, or postmenopausal hormone use, or by breast cancer subtypes.Circulating MMP1, 3, and 7 levels do not appear to be predictive of overall breast cancer risk.

Previous studies have suggested that migraineurs are at decreased risk for developing breast cancer. Further prospective studies are warranted to confirm these results. In addition, studies evaluating migraine characteristics (e.g., migraine subtypes and frequency) are lacking. We conducted a prospective cohort study among 39,696 participants in the Women’s Health Study who were 45 years and older at study entry. Information on migraine was self-reported with good validation rates. Incident breast cancer cases were confirmed by medical record review. We distinguished the following major endpoints: any breast cancer, a combined endpoint of invasive and in situ cases, in situ breast cancer only, and invasive breast cancer only. Cox proportional hazards models were used to calculate age- and multivariable-adjusted hazard ratios (HRs) and 95 % confidence intervals (95 % CI). A total of 7,318 (18.4 %) women reported any migraine. During a mean follow-up time of 13.6 years, 432 in situ and 1,846 invasive breast cancer cases occurred. Migraine was not associated with breast cancer risk. The multivariable-adjusted HRs (95 % CI) were 1.10 (0.99–1.22) for any breast cancer, 1.06 (0.83–1.35) for in situ breast cancer, and 1.11 (0.99–1.25) for invasive breast cancer. The risk for developing breast cancer differed according to hormone receptor status with a suggestion of increased risks for hormone receptor negative tumors (HR ER−/PR− : 1.28, 95 % CI: 0.96–1.71). We did not observe meaningful differences with regard to histologic subtype or according to migraine aura status or migraine attack frequency. Results of our study do not support the hypothesis that migraineurs have a decreased risk for breast cancer.

The association between infectious mononucleosis (IM) and risk of breast cancer is unclear; no prospective studies have examined this relationship. We examined self-reported history and age at IM in relation to risk of invasive breast cancer.Self-reported history and age at IM were examined in relation to risk of invasive breast cancer in a large cohort of women, the Nurses' Health Study II (81,807 women followed from 1989 to 2007). Through questionnaires, women were asked whether they ever had IM and if so, at what age. During follow-up, 2,349 cases of invasive breast cancer were documented. Cox proportional hazards regression was used to estimate relative risks (RR) and 95 % confidence intervals (CI) for the association of IM with breast cancer.The multivariable-adjusted RR for history of IM and risk of invasive breast cancer was 1.00 (95 % CI: 0.90-1.11). Similar null results were obtained when estrogen receptor/progesterone receptor positive and negative tumors were considered separately. There were no clear patterns of association between age at IM and risk of breast cancer: compared to women with no history of IM, those who were ≤15 years old when they had IM were at lower risk (RR: 0.77; 95 % CI: 0.60, 0.97), but there was no association for women who had IM at ages 16-19, 20-24, or 30+. However, an increased RR (1.45; 95 % CI: 1.02-2.04) was observed for women who had IM at ages 25-29.Results of this large prospective study do not support a clear association between history of clinical IM and risk of invasive breast cancer.

Exercise is a modifiable factor that is inversely related to risk for breast cancer. To determine if physical activity has a preventative effect on development of premalignant breast lesions, we examined the association between exercise and the incidence of proliferative benign breast disease. In 1997, the Nurses’ Health Study II cohort reported levels of physical activity during adolescence and adulthood using a validated recall instrument. We followed 40,318 participants free from benign breast disease (BBD) or cancer prospectively for four years and confirmed 232 proliferative benign breast lesions by centralized pathology review. Cox proportional hazards models estimated the age-adjusted and multivariable-adjusted relative risks for physical activity and proliferative benign breast disease. We observed a significant inverse association for walking and incidence of BBD, risk was reduced by 9% per hour of walking (95% CI 0% to 17%), (p trend = 0.05). Despite a small number of cases, risk of columnar cell lesions also suggested an inverse association with strenuous activity (RR for 4 or more hours of strenuous activity per week = 0.62; 0.31–1.22 compared to

There is considerable evidence that birth weight is positively associated with breast cancer risk, and seven single-nucleotide polymorphisms (SNPs) have been conclusively associated with this risk. We have hypothesized that breast cancer susceptibility loci may have a greater influence on breast cancer risk among women with higher birth weight, who are expected to have a larger pool of mammary stem cells that are susceptible to malignant transformation.In the context of a nationwide, population-based case-control study in Sweden, we retrieved recorded birth weight for 693 breast cancer cases and 747 control women who were also genotyped for most or all of the seven recently documented breast cancer susceptibility SNPs: rs2981582, rs12443621, rs8051542, rs3803662, rs889312, rs13281615, and rs3817198.We grouped heterozygotes with homozygotes for the wild-type allele, and we found a marginally significant interaction (p~0.07) between birth weight and rs2981582 (FGFR2), the genotype repeatedly identified as the top hit in genome-wide association studies. There were similar, though not significant, patterns for the other six SNPs.Although our findings require confirmation, we found suggestive evidence that genetic susceptibility modifies the positive association of birth weight with breast cancer.