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Chronic stress affects immune function and hormonal signaling and has been hypothesized to be associated with breast cancer, although results from the few prior studies are mixed and have not examined potential differences by estrogen receptor (ER) status. Using the Women's Health Initiative study, we included 76,951 postmenopausal women followed for events for a median of 16.7 years to investigate the association between baseline self-reported stressful life events and incident breast cancer by ER status and whether the association was modified by social support. We generated Cox proportional hazards models adjusting for demographic, clinical, lifestyle/behavioral, and social factors to estimate HRs and 95% confidence intervals (95%CI). The mean age was 63 (SD, 7.3), and majority of participants were White race (83.5%) and married or in a marriage-like relationship (63.0%). In analyses stratified by ER status, there was no relationship between stressful life events and ER-positive breast cancer. In contrast, compared with women in the lowest quartile, those in higher quartiles had an increased risk of ER-negative breast cancer, where those in quartile 4 had the highest risk (Quartile 4 vs. Quartile 1; HR = 1.30; 95%CI, 1.01–1.68; Ptrend = 0.050). Moreover, associations were stronger for the highest versus lowest quartile of stressful life events among widowed women (HR = 2.39; 95%CI, 1.29–4.44; Pinteraction Prevention Relevance: Epidemiologic studies on the association between psychosocial stress and breast cancer risk remain inconsistent, while investigation of whether the association differs by ER status is limited. In this prospective cohort of postmenopausal women, high experiences of stressful life events were positively associated with ER-negative disease but not ER-positive.

Supplemental Figure 1: Presents the flow chart of women that participated in the observational study that were included in the analytical sample.

Supplemental Table 1: Describes the Stressful Life Events and Social Support scales used in the study.

Chronic stress affects immune function and hormonal signaling and has been hypothesized to be associated with breast cancer, although results from the few prior studies are mixed and have not examined potential differences by estrogen receptor (ER) status. Using the Women's Health Initiative study, we included 76,951 postmenopausal women followed for events for a median of 16.7 years to investigate the association between baseline self-reported stressful life events and incident breast cancer by ER status and whether the association was modified by social support. We generated Cox proportional hazards models adjusting for demographic, clinical, lifestyle/behavioral, and social factors to estimate HRs and 95% confidence intervals (95%CI). The mean age was 63 (SD, 7.3), and majority of participants were White race (83.5%) and married or in a marriage-like relationship (63.0%). In analyses stratified by ER status, there was no relationship between stressful life events and ER-positive breast cancer. In contrast, compared with women in the lowest quartile, those in higher quartiles had an increased risk of ER-negative breast cancer, where those in quartile 4 had the highest risk (Quartile 4 vs. Quartile 1; HR = 1.30; 95%CI, 1.01–1.68; Ptrend = 0.050). Moreover, associations were stronger for the highest versus lowest quartile of stressful life events among widowed women (HR = 2.39; 95%CI, 1.29–4.44; PinteractionPrevention Relevance:Epidemiologic studies on the association between psychosocial stress and breast cancer risk remain inconsistent, while investigation of whether the association differs by ER status is limited. In this prospective cohort of postmenopausal women, high experiences of stressful life events were positively associated with ER-negative disease but not ER-positive.

Supplemental Table 2: Presents the hazard ratios for the association between Stressful Life Events and incident breast cancer by participant characteristics and estrogen receptor status.

The dual effect of pregnancy on breast cancer risk has long been recognized. The short-term increase in breast cancer after pregnancy, particularly cancers that are more aggressive, contrasts starkly with the longer-term decrease. It remains unclear how these opposing effects of pregnancy relate to molecular subtypes of breast cancer, which impacts translation. Several methodologic challenges remain related to the study and operationalization of key constructs, which remain complicated by the correlation between age at pregnancies, overall parity, and intervals between pregnancies and cancer diagnoses. In this issue of CEBP, Vohra and colleagues address some of these major gaps as well as present novel data on the breast tissue microenvironment. The increasing incidence of invasive breast cancer in women under age 50 years requires improved clinical translation and identification of higher risk women after pregnancy. Thus, it is crucial to address the gaps in our biological understanding of pregnancy-related breast cancers. See related article by Vohra et al., p. 561

Purpose Incidence of breast cancer (BC), particularly in young women, are rising in India. Without population-based mammography screening, rising rates cannot be attributed to screening. Investigations are needed to understand the potential drivers of this trend. Methods An international team of experts convened to discuss the trends, environmental exposures, and clinical implications associated with BC in India and outlined recommendations for its management. Results Panels were structured across three major BC themes (n = 10 presentations). The symposium concluded with a semi-structured Think Tank designed to elicit short-term and long-term goals that could address the challenges of BC in India. Conclusion There was consensus that the prevalence of late-stage BC and the high BC mortality rates are associated with the practice of detection, which is primarily through clinical and self-breast exams, as opposed to mammography. Triple-Negative BC (TNBC) was extensively discussed, including TNBC etiology and potential risk factors, the limited treatment options, and if reported TNBC rates are supported by rigorous scientific evidence. The Think Tank session yielded long-term and short-term goals to further BC reduction in India and included more regional etiological studies on environmental exposures using existing India-based cohorts and case–control studies, standardization for molecular subtyping of BC cases, and improving the public’s awareness of breast health.

Background: Studies in women with pathogenic variants in BRCA1 or BRCA2 suggest that underlying breast cancer (BC) risk modifies the associations between pregnancy-related factors and BC risk. Less is known about whether the associations are modified across a range of predicted absolute BC risk based on age and the extent of BC family history. Objective: Examine the association between pregnancy-related factors and BC risk and modification by predicted absolute BC risk in the Prospective Family Study Cohort (ProF-SC) with women enrolled between 1992-2011 and a median 10.0 years of follow-up time. Methods: ProF-SC includes the six international sites of the Breast Cancer Family Registry [USA, Canada, and Australia] and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). 17,274 women with 943 prospectively ascertained BC cases were eligible for the prospective analysis with 87% of cases self-identifying as non-Hispanic White. Questionnaires at study entry assessed self-reported pregnancy-related factors (parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, breastfeeding, and age at menarche). We used Cox proportional hazards regression models with age as a time scale to estimate Hazard Ratios (HR) and the 95% Confidence Intervals (CI) for each reproductive variable (main effect) and examined modification by predicted absolute risk of BC, measured by a 1-year absolute risk score (continuous) estimated by the BOADICEA (interaction effect). We also examined associations stratified by estrogen receptor (ER) subtype. Results: Women with a first FTP at age ≥30 vs. 20% increased risk of ER-negative BC compared to first FTP at age Conclusion: The association between pregnancy-related factors and BC risk are modified by predicted absolute BC risk, with stronger associations observed for ER-negative BC. Women at higher absolute BC risk may benefit from more frequent BC monitoring following childbirth. Citation Format: Jasmine A. McDonald, Yuyan Liao, Esther M. John, Allison W. Kurian, Jeanine M. Genkinger, Saundra S. Buys, John L. Hopper, kConFab Investigators, Mary Beth Terry. Timing of pregnancy-related factors and breast cancer risk for women across a range of absolute risk. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4176.

Introduction: Chronic stress affects immune function and hormonal signaling and has been hypothesized to be associated with breast cancer, although results from the few prior studies are mixed and have not examined potential differences by estrogen receptor (ER) status. We investigated the relationship between stressful life events and incident breast cancer by ER status among postmenopausal women. We further evaluated whether this association is modified by social support. Methods: Our analysis included 76,951 postmenopausal women enrolled in the Women’s Health Initiative. Participants were followed for events for up to 26 years (median, 16.7). We generated Cox proportional hazards models adjusting for demographic, clinical, lifestyle/behavioral, and social factors to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for associations between baseline self-reported stressful life events and incident breast cancer by ER status. Results: The mean age was 63 (SD 7.3), and majority of participants were White race (83.5%) and married or in a marriage-like relationship (63.0%). In analyses stratified by ER status, there was no relationship between stressful life events and ER-positive breast cancer. In contrast, compared to women in the lowest quartile, those in higher quartiles had an increased risk of ER-negative breast cancer, where those in quartile 4 had the highest risk (Quartile 4 vs Quartile 1; HR=1.30; 95%CI 1.01-1.68; Ptrend=0.050). Additionally, associations were stronger for the highest versus lowest quartile of stressful life events among widowed women (HR=2.39; 95%CI 1.29-4.44; Pinteraction Conclusion: In this cohort of postmenopausal women, higher experiences of pre-diagnostic stressful life events were associated with increased risk of ER-negative breast cancer. Citation Format: Wayne R. Lawrence, Jasmine A. McDonald, Faustine Williams, Meredith S. Shiels, Neal D. Freedman, Ziqiang Lin, Jared W. Magnani. Psychosocial stress, social support, and incident breast cancer by estrogen receptor status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3011.

Background Earlier onset of breast development (thelarche) is associated with increased breast cancer risk. Identifying modifiable factors associated with earlier thelarche may provide an opportunity for breast cancer risk reduction starting early in life, which could especially benefit girls with a greater absolute risk of breast cancer due to family history. Methods We assessed associations of maternal pre-pregnancy body mass index (BMI), physical activity during pregnancy, gestational weight gain and daughters’ weight and length at birth with age at thelarche using longitudinal Weibull models in 1031 girls in the Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study—a prospective cohort of girls, half of whom have a breast cancer family history (BCFH). Results Girls whose mothers had a pre-pregnancy BMI of ≥25 and gained ≥30 lbs were 57% more likely to experience earlier thelarche than girls whose mothers had a pre-pregnancy BMI of Conclusion Earlier thelarche, a breast cancer risk factor, was associated with three potentially modifiable maternal risk factors—pre-pregnancy BMI, gestational weight gain and physical inactivity—in a cohort of girls enriched for BCFH.

Earlier pubertal development is only partially explained by childhood body mass index; the role of other factors, such as childhood infections, is less understood. Using data from the LEGACY Girls Study (North America, 2011–2016), we prospectively examined the associations between childhood viral infections (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) 1, HSV2) and pubertal timing. We measured exposures based on seropositivity in premenarcheal girls (n = 490). Breast and pubic hair development were classified based on mother-reported Tanner Stage (TS) (TS2+ compared with TS1), adjusting for age, body mass index, and sociodemographic factors. The average age at first blood draw was 9.8 years (standard deviation, 1.9 years). The prevalences were 31% CMV+, 37% EBV+, 14% HSV1+, 0.4% HSV2+, and 16% for both CMV+/EBV+ coinfection. CMV+ infection without coinfection was associated with developing breasts an average of 7 months earlier (hazard ratio (HR) = 2.12, 95% confidence interval (CI): 1.32, 3.40). CMV infection without coinfection and HSV1 and/or HSV2 infection were associated with developing pubic hair 9 months later (HR = 0.41, 95% CI: 0.24, 0.71, and HR = 0.42, 95% CI: 0.22, 0.81, respectively). Infection was not associated with menarche. If replicated in larger cohorts with blood collection prior to any breast development, this study supports the hypothesis that childhood infections might play a role in altering pubertal timing.

We examined the relationship between intrauterine dichlorodiphenyltrichloroethane (DDT) exposure (o,p’-DDT, p,p’-DDT, and p,p’-DDE) and mammographic breast density (MBD) in midlife, one of the strongest risk factors for breast cancer. We focused our analyses on o,p’-DDT exposure given our previous report of a positive association between intrauterine o,p’-DDT exposure and daughter’s breast cancer (BC) risk. Here we estimated associations of intrauterine serum DDTs with MBD in 224 daughters of women in the Child Health and Development Studies pregnancy cohort whose mothers did not develop BC (MBCa−) and 156 daughters whose mothers did develop BC (MBCa+). In MBCa+ daughters, highest relative to lowest quartile of o,p’-DDT exposure was associated with a 17-unit higher dense area (95% CI = 2.6–31.2; Ptrend = 0.01). We did not observe an association between o,p’-DDT and density measures in MBCa− daughters. MBD, an intermediate marker of BC risk, may be affected by intrauterine DDT exposures; MBCa status may modify the association.

Background Early life adversity and infections may theoretically affect the timing and effort of reproductive development. We examined associations of childhood adversity and exposure to tonsillitis with age at menarche in women age 40-64 years. Methods A multi-ethnic cohort of 394 women reported on exposure to parental maltreatment and maladjustment during childhood ( Results The average age at menarche was 12.6 years, and was significantly lower for women who lived with a mentally ill caregiver (M = 12.4 (95% CI: 11.7-13.0)) and those with a history of tonsillitis (M = 12.6 (95% CI: 12.0-13.2)). In adjusted multivariable models, living with a mentally ill caretaker (RR = 1.5, 95% CI: 1.0-2.1) and a having a history of tonsillitis (RR = 1.7, 95% CI: 1.3-2.4) were associated with increased risk of early menarche compared with women without these exposures. Cumulative and other specific adversities were not statistically associated with early menarche. Conclusions These findings support growing evidence that early life experiences may influence reproductive development. Key messages Early life adversity related to living with mentally ill caretakers and a history of tonsillitis is associated with earlier menarche in racial/ethnic minority and immigrant women.

The National Cancer Institute (NCI) has established an online repository of evidence-based cancer control programs (EBCCP) and increasingly calls for the usage of these EBCCPs to reduce the cancer burden. To inventory existing EBCCPs and identify remaining gaps, we summarized NCI’s EBCCPs relevant to reducing breast cancer risk with an eye towards interventions that address multiple levels of influence in populations facing breast cancer disparities. For each program, the NCI EBCCP repository provides the following expert panel determined summary metrics: (a) program ratings (1–5 scale, 5 best) of research integrity, intervention impact, and dissemination capability, and (b) RE-AIM framework assessment (0–100%) of program reach, effectiveness, adoption, and implementation. We quantified the number of EBCCPs that met the quality criteria of receiving a score of ≥3 for research integrity, intervention impact, and dissemination capability, and receiving a score of ≥50% for available RE-AIM reach, effectiveness, adoption, and implementation. For breast cancer risk reduction, we assessed the presence and quality of EBCCPs related to physical activity (PA), obesity, alcohol, tobacco control in early life, breastfeeding, and environmental chemical exposures. Our review revealed several major gaps in EBCCPs for reducing the breast cancer burden: (1) there are no EBCCPs for key breast cancer risk factors including alcohol, breastfeeding, and environmental chemical exposures; (2) among the EBCPPs that exist for PA, obesity, and tobacco control in early life, only a small fraction (24%, 17% and 31%, respectively) met all the quality criteria (≥3 EBCCP scores and ≥50% RE-AIM scores) and; (3) of those that met the quality criteria, only two PA interventions, one obesity, and no tobacco control interventions addressed multiple levels of influence and were developed in populations facing breast cancer disparities. Thus, developing, evaluating, and disseminating interventions to address important risk factors and reduce breast cancer disparities are needed.

Prior to the recommended age for population-based breast cancer screening by mammography, which ranges from 40-50 years depending on guidelines, the main way to identify higher risk women for earlier breast cancer (BC) screening to improve outcomes and discuss targeted chemoprevention is through specific clinical guidelines which are largely based on family history of breast cancer and known mutations in breast cancer susceptibility genes. The annual percent change (APC) in early-onset BC continues to rise, with the higher early-onset cancer burden and mortality continuing to be seen in non-Hispanic black (NHB) women compared to non-Hispanic white (NHW) women. Coupled with the increasing incidence overall as well as the lower percent of BC family history reported in NHB women compared with that of NHW women means that continued reliance on guidelines to identify women for genetic screening and initiation of early BC screening based largely on family history could lead to even greater BC health inequities. The similarity in the prevalence of mutations in key BC susceptibility genes between NHB and NHW women contrasts sharply to the differences in age-specific incidence rates between NHB and NHW women, supporting that there must be environmental modifiers that are contributing to the increased incidence in NHB women. This reality further argues for identifying NHB women early in adulthood through genetic testing who may benefit from tailored BC risk-reduction programs and early BC screening.

Childhood adversities (CAs) and infections may affect the timing of reproductive development. We examined the associations of indicators of CAs and exposure to tonsillitis and infectious mononucleosis (mono) with age at menarche. A multiethnic cohort of 400 women (ages 40–64 years) reported exposure to parental maltreatment and maladjustment during childhood and any diagnosis of tonsillitis and/or mono, infections primarily acquired in early life and adolescence, respectively. We used linear and relative risk regression models to examine the associations of indicators of CAs individually and cumulatively, and history of tonsillitis/mono with an average age at menarche and early onset of menarche (&lt, 12 years of age). In multivariable models, histories of mental illness in the household (RR = 1.44, 95% CI: 1.01–2.06), and tonsillitis diagnosis (RR = 1.67, 95% CI: 1.20–2.33) were associated with early menarche (&lt, 12 years), and with an earlier average age at menarche by 7.1 months (95% CI: −1.15, −0.02) and 8.8 months (95% CI: −1.26, −0.20), respectively. Other adversities indicators, cumulative adversities, and mono were not statistically associated with menarcheal timing. These findings provided some support for the growing evidence that early life experiences may influence the reproductive development in girls.

Measuring systemic chronic inflammatory markers in the blood may be one way of understanding the role of inflammation in breast cancer risk, and might provide an intermediate outcome marker in prevention studies. Here, we present the results of a systematic review of prospective epidemiologic studies that examined associations between systemic inflammatory biomarkers measured in blood and breast cancer risk. From 1 January 2014 to 20 April 2020, we identified 18 unique studies (from 16 publications) that examined the association of systemic inflammatory biomarkers measured in blood with breast cancer risk using prospectively collected epidemiologic data. Only one marker, C-reactive protein, was studied extensively (measured in 13 of the 16 publications), and had some evidence of a positive association with breast cancer risk. Evidence associating other inflammatory biomarkers and more comprehensive panels of markers with the development of breast cancer is limited. Future prospective evidence from expanded panels of systemic blood inflammatory biomarkers is needed to establish strong and independent links with breast cancer risk, along with mechanistic studies to understand inflammatory pathways and demonstrate how breast tissue responds to chronic inflammation. This knowledge could ultimately support the development and evaluation of mechanistically driven interventions to reduce inflammation and prevent breast cancer.

BACKGROUND: Building upon our earlier findings of significant associations between hair dye and relaxer use with increased breast cancer risk, we evaluated associations of select characteristics of use with breast tumor clinicopathology. METHODS: Using multivariable-adjusted models we examined the associations of interest in a case-only study of 2,998 women with breast cancer, overall and stratified by race and estrogen receptor (ER) status, addressing multiple comparisons using Bonferroni correction. RESULTS: Compared to salon application of permanent hair dye, home kit and combination application (both salon and home kit application) were associated with increased odds of poorly differentiated tumors in the overall sample. This association was consistent among Black (home kit: OR 2.22, 95% CI: 1.21–5.00; combination: OR 2.46, 95% CI: 1.21–5.00), but not White women, and among ER+ (home kit: OR 1.47, 95% CI: 0.82–2.63; combination: OR 2.98, 95% CI: 1.62–5.49) but not ER− cases. Combination application of relaxers was associated with increased odds of tumors >2.0 cm vs.

High birth weight is associated with increased breast cancer risk and, less consistently, with higher mammographic density. In contrast, adolescent body size has been consistently, negatively associated with both MD and breast cancer risk. It is unclear when the direction of these associations changes and whether weight gain in infancy is associated with MD. We evaluated the associations of birth weight and postnatal weight (measured at 4 months, 1 year, and 4 years) by absolute and velocity measures (relative within-cohort percentile changes) with adult mammographic density, assessed using a computer-assisted thresholding program (Cumulus), using linear regression models with generalized estimating equations to account for correlation between siblings in the Early Determinants of Mammographic Density study (1959-2008; n = 700 women with 116 sibling sets; mean age = 44.1 years). Birth weight was positively associated with dense area (per 1-kg increase, β = 3.36, 95% confidence interval (CI): 0.06, 6.66). Weight gains from 0 months to 4 months and 1 year to 4 years were negatively associated with dense area (for 10-unit increase in weight percentile, β = -0.65, 95% CI: -1.23, -0.07, and β = -1.07, 95% CI: -1.98, -0.16, respectively). Findings were similar in the sibling subset. These results support the hypothesis that high birth weight is positively associated with increased breast density and suggest that growth spurts starting in early infancy reduce mammographic dense area in adulthood.

Prior studies in the Child Health and Development Studies (CHDS) found in utero exposure to the pesticide, dichlorodiphenyltrichloroethane (DDT), increased breast cancer risk by age 52. Mammographic density is considered a primary risk factor for breast cancer. We conducted a study of 309 daughters from the CHDS to examine in utero DDT exposure and mammographic density in midlife. Among daughters with high (>75th percentile) exposure to p,p'-Dichlorodiphenyldichloroethylene (DDE), p,p'-DDT was significantly correlated with increased dense area and percent density regardless of her body mass in midlife. In the subset of women with lower (

Background Epidemiological studies have found that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with increased risk for neural tube defects (NTDs). Aberrant DNA methylation, excessive apoptosis, and oxidative stress have been implied as the mechanism underlying the association between PAH exposure and NTDs, respectively. However, the role of DNA methylation aberration of apoptotic initiator CASP8 (caspase-8, apoptosis-related cysteine peptidase) in the formation of NTDs in association with PAH exposure is not known. By combining a case–control study and mouse model, we aimed to explore the full spectrum of the links from PAH exposure, oxidative stress, CASP8 methylation change, caspase-8 activation, apoptosis, to NTD formation. Results Hypomethylation of CASP8 promoter was noticed in the microarray profiled by Infinium HumanMethylation450 BeadChip using neural tissues from 10 terminated NTD fetuses and 8 terminated non-malformed fetuses (14 CpG sites, with β difference ranging between 8.8 and 26.3%), and was validated in a larger case–control sample performed with neural tissues from 80 NTD cases and 32 non-malformed fetuses, using the Sequenom MassARRAY system (7 CpG sites). Hypomethylation of CASP8 was a risk factor for NTDs (aOR = 1.11; 95% CI, 1.05–1.17) based on the logistic regression model. According to Pearson’s correlation, methylation levels of CASP8 were inversely correlated with PAH concentrations in maternal serum and with oxidative stress markers in fetal neural tissues (p < 0.05). In the animal study, increased NTD rates (13.5% frequency), Casp8 hypomethylation, caspase-8 upregulation, increased caspase-8 cleavage, and excessive apoptosis were found in mouse embryos cultured with benz(a)pyrene (BaP) in vitro. Antioxidant N-acetyl-L-cysteine (NAC) and BaP co-treatment attenuated the changes found in BaP treatment group. Conclusions Hypomethylation of Casp8 promoter is associated with the formation of NTDs, and Casp8 hypomethylation may be induced by oxidative stress that resulted from exposure to PAHs. Electronic supplementary material The online version of this article (10.1186/s13148-019-0673-6) contains supplementary material, which is available to authorized users.

The decline in age of pubertal timing has serious public health implications ranging from psychosocial adjustment problems to a possible increase in reproductive cancers. One biologically plausible explanation for the decline is a decrease in exposures to infections. To systematically review studies that assess the role of infection in pubertal timing, Medline, Web of Science and EMBASE were systematically searched and retrieved studies were reviewed for eligibility. Eligible studies examined the association between infections, including microbial exposures, and physical pubertal characteristics (breast, genitalia and pubic hair development) or age at menarche. We excluded studies that were published in a language other than English, focused on precocious puberty, were case studies, and/or included youth with autoimmune diseases. We report on study design, population characteristics, measurement of infection and puberty and the main effects of infection on pubertal development. Based on our search terms we identified 1372 unique articles, of which only 15 human and five animal studies met our eligibility criteria. Not all studies examined all outcomes. Infection was associated with later breast development (4/4 human studies), with less consistent evidence for genitalia and pubic hair development. Seven studies assessed age at menarche with inconsistent findings (three supporting later, four no association). We conclude that a small but consistent literature supports that infection is associated with later breast development; the evidence for other pubertal events and age at menarche is less clear. Where fewer childhood infections coincide with the rise in incidence of hormone-related cancers.

Introduction: In our previous findings from the Women’s Circle of Health Study (WCHS), we observed statistically significant associations between use of hair dye and relaxer, which contain potentially mutagenic and endocrine-disrupting chemicals, and increased breast cancer risk. In the current analysis, we sought to expand upon our earlier findings by assessing associations between hair product use and breast tumor clinicopathology. Methods: Risk factor data (including characteristics of hair product use) were collected through in-person interviews, and tumor clinicopathology data were abstracted from available pathology records of 2,998 breast cancer cases (2,227 Black, 771 White). Associations between hair product use and tumor clinicopathology were analyzed using multivariable-adjusted, binomial and multinomial logistic regression models. Further analysis was performed in subsets by race and estrogen receptor (ER) status. Results: Numerous characteristics of hair product use were associated with more aggressive tumor features. Longer (>10 years) use of relaxers and earlier exposure to relaxers (≤12 years old at first use) were associated with increased odds of poorly differentiated tumors (OR 2.15, 95% CI: 1.08-4.28 and OR 2.00, 95% CI: 1.05-3.82, respectively). History of regular relaxer use (OR 1.51, 95% CI: 1.23-1.87) and dual use of both hair dyes and relaxers (OR 1.40, 95% CI: 1.02-1.92) were associated with increased odds of ER- status. Compared to sole salon application, utilization of both salon and home- kit application types for hair dyes was associated with increased odds of higher tumor grade (moderately differentiated: OR 1.74, 95% CI: 1.05-2.87; poorly differentiated: OR 2.52, 95% CI: 1.51-4.20). These associations were consistent among Black, but not White, women. Combination use of salon and home-kit relaxer application types was associated with increased odds of tumors >2.0 cm (OR 1.88, 95% CI: 1.27-2.77). Conclusions: While recent research has supported a connection between hair product use and breast cancer risk, this is the first study to examine the associations of hair product use with breast tumor features. Our findings showed that certain characteristics, particularly the magnitude of exposure to these products and application types of hair dye and relaxer, are associated with tumor features that are indicative of more aggressive phenotypes, including higher grade and ER- status. These findings generate new hypotheses about the potential impact of hair product use on breast cancer outcomes, warranting further study. Citation Format: Rohan Rao, Jasmine A. McDonald, Emily S. Barrett, Dede Teteh, Susanne Montgomery, Bo Qin, Yong Lin, Chi-Chen Hong, Christine B. Ambrosone, Kitaw Demisse, Elisa V. Bandera, Adana A.M. Llanos. Associations of characteristics of hair dye and relaxer use with tumor clinicopathologic features among Black and White women with breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-181.

Studies examining intrauterine environmental exposures and breast cancer risk are challenged by the long induction period between exposure and breast cancer development. One strategy to address this challenge is to examine the relationship between exposures and intermediate markers of breast cancer risk. Mammographic breast density (MBD) is considered an intermediate marker for breast cancer—having mostly dense breasts is associated with nearly a 4-fold increase in breast cancer as compared with having mostly fatty breasts. Here we examined the relation between intrauterine dichlorodiphenyltrichloroethane (DDT) exposure (o,p’-DDT, p,p’-DDT, and p,p’-DDE) to MBD in midlife. We focused our analyses on o,p’-DDT exposure when mutually adjusted for p,p’-DDE given our previous report of a positive association between intrauterine o,p’-DDT exposure and daughters’ breast cancer (BC) risk. We estimated associations of early postpartum serum DDTs with MBD in 224 daughters of women in the Child Health and Development Studies pregnancy cohort whose mothers did not develop BC (MBCa-negative) and 156 daughters whose mothers did develop BC (MBCa-positive). In MBCa-positive daughters, highest relative to lowest quartile of o,p’-DDT exposure was associated with a 17-unit higher dense area (95% CI= 2.6-31.2; Ptrend=0.01); associations persisted after adjusting for p,p’-DDT. MBD, an important intermediate marker of BC risk, may be affected by intrauterine DDT exposures; MBCa status may modify the association. Citation Format: Jasmine A. McDonald, Piera M. Cirillo, Parisa Tehranifar, Nickilou Y. Krigbaum, Natalie Engman, Barbara A. Cohn, Mary Beth Terry. In utero DDT exposure and breast density in early menopause by maternal history of breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A17.

An earlier age at pubertal development is associated with increased breast cancer risk, and Westernized countries are observing earlier ages of pubertal timing in girls. While increased rates of childhood obesity are associated with earlier ages of pubertal development, earlier ages of puberty are also observed in countries that are not experiencing high rates of childhood obesity. Prior evidence from a birth cohort in Hong Kong suggests that early life infections, as measured by hospitalizations, is associated with pubertal onset. Emerging evidence suggests that early life and childhood exposures to infection may impact pubertal development. Therefore, we aimed to assess whether indirect measures of infections in infancy (birth-12 months) and early childhood (1-5 years) are associated with the age of onset of puberty (menarche and breast and pubic hair development). We used data from the Infection Questionnaire from the multisite prospective LEGACY Girls Study where mothers/guardians reported on daughters’ indirect exposure to infection (daycare attendance, antibiotic use, physician visit due to fever, hospitalization due to infection) and specific exposure to infections (e.g., tonsillitis, cold sores). Mothers/guardians reported on daughters’ age at first menses and the onset of breast and pubic hair development using Tanner Staging (as defined as Tanner Stage 2 or higher). We used Cox Proportional Hazard Ratio (HR) models to examine the prospective association between infection history and pubertal timing. We considered site, race/ethnicity, and maternal education as possible confounders. In 615 girls (average age (SD) 9.5 (2.4) years) whose mother/guardians completed the Infection Questionnaire, 65% were white non-Hispanic, 18% were Hispanic, 5% were Black non-Hispanic, and 9% were Asian. Sixty-nine percent of mothers/guardians had a college degree or higher. We assessed frequency of infectious exposures across infancy and early childhood where 73% of girls ever used antibiotics, 59% of girls ever had an ear infection, 59% of girls ever attended daycare over 10 hours per week, 29% of girls visited a physician due to fever (measured in childhood only), 36% of mothers reported girls having 2 or more infections, and 6% of girls were ever hospitalized due to infection. In multivariable models controlled for socioeconomic and maternal factors, earlier age of pubic hair development was associated with hospitalization due to infection compared to never hospitalized (HR=1.53, 95% CI=1.07-2.21) and ever antibiotic use compared to never antibiotic use (HR=1.31, 95% CI=1.03-1.68). Compared to never, multivariable models suggested that earlier age at menarche was associated with physician visit due to fever (HR=1.30, 95% CI=1.04-1.63). We observed no association between infectious exposures and earlier breast development. These results suggest that infancy and childhood infectious exposures may be related to earlier pubertal development, but more studies are needed to confirm these findings. Citation Format: Yun Huang, Irene L. Andrulis, Angela R. Bradbury, Saundra S. Buys, Mary B. Daly, Esther M. John, Lisa A. Schwartz, Mary Beth Terry, Jasmine A. McDonald. Infancy and childhood infections and pubertal timing in the LEGACY Girls’ Study [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A14.

Polycyclic aromatic hydrocarbons (PAH) are common environmental pollutants that result from incomplete combustion of biomass and fossil fuels. PAH have endocrine-disrupting properties and are known animal carcinogens. Evidence from case-control studies suggests an association between PAH and breast cancer risk, but longitudinal research on PAH exposure during critical windows of susceptibility, such as prenatally and in early life, is limited. The purpose of this study was to prospectively examine whether prenatal exposure to PAH is associated with breast tissue composition, an intermediate marker of breast cancer risk, in adolescent girls. We studied 105 adolescent girls in the Columbia Center for Children’s Environmental Health (CCCEH) birth cohort, which recruited nonsmoking African American and Dominican American pregnant women living in three low-income neighborhoods in New York City from 1998-2006. Women wore a small backpack holding a personal air monitor for 2 consecutive days during the 3rd trimester of pregnancy, which measured concentrations of pyrene and 8 other carcinogenic PAH (summed and categorized into tertiles for analysis). Girls completed a follow-up clinic visit in adolescence (ages 11.2-19.6 years, median=15.8), at which time breast tissue composition was measured by optical spectroscopy (OS). OS is a novel and noninvasive tool that provides a broad compositional view of the breast by capturing variation in the amount of water, lipid, oxy-hemoglobin, deoxy-hemoglobin, and collagen, as well as overall cellular and connective tissue density. OS measured red and near-infrared light transmission of 7 wavelengths (650-1060 nm) at 4 source-detector distances in each breast quadrant, resulting in 16 overlapping tissue volumes. Principal component analysis was used to reduce spectral data and generate principal component (PC) scores for each participant, which were averaged over both breasts. We used multivariable linear regression to examine associations of prenatal PAH measures (pyrene and Σ8 PAH) with each of the first 4 OS PCs, which explained >99% of the spectral variation in the sample. Models were adjusted for age, ethnicity, body mass index (BMI) at time of OS measurement, age at breast development, and mothers’ prepregnancy BMI. After adjusting for covariates, PC1 scores were significantly lower on average in the highest compared to lowest tertile of prenatal ambient Σ8 PAH (β = -0.42, 95% CI = -0.81 to -0.02, p = 0.04). PC1 covered 91.8% of the spectral variations and represents overall light attenuation from higher scattering due to higher cellularity and connective tissues. PC1 also mapped to multiple chromophores including hemoglobin and collagen. No associations were found between prenatal ambient Σ8 PAH and PCs 2-4, and no associations with OS PCs were found for pyrene. To conclude, we found evidence suggesting that prenatal exposure to PAH is associated with breast tissue composition in adolescent girls. Citation Format: Rebecca D. Kehm, Lothar Lilge, E. Jane Walter, Nur Zeinomar, Jasmine A. McDonald, Parisa Tehranifar, Julie B. Herbstman, Rachel L. Miller, Mary Beth Terry. Prenatal exposure to polycyclic aromatic hydrocarbons and breast tissue composition in adolescent girls [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A15.

Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites (CpGs) in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959–1964 and measured DNA methylation in blood (granulocytes) collected in 2001–2007 (mean age: 43 years). Seventeen CpGs were differentially methylated by MSP, with multiple CpGs mapping to CYP1A1, MYO1G, AHRR, and GFI1. These associations were consistent in direction with prior studies (e.g., MSP associated with more and less methylation in AHRR and CYP1A1, respectively) and, with the exception of AHRR CpGs, were not substantially altered by adjustment for active smoking. These preliminary results confirm prior prospective reports that MSP influences the offspring DNA methylation, and extends the timeframe to midlife, and suggest that these effects may persist into adulthood, independently of active smoking.

Background Select hair products contain endocrine disrupting chemicals (EDCs) that may affect breast cancer risk. We hypothesize that, if EDCs are related to breast cancer risk, then they may also affect two important breast cancer risk factors: age at menarche and mammographic breast density. Methods In two urban female cohorts (N = 248): 1) the New York site of the National Collaborative Perinatal Project and 2) the New York City Multiethnic Breast Cancer Project, we measured childhood and adult use of hair oils, lotions, leave-in conditioners, root stimulators, perms/relaxers, and hair dyes using the same validated questionnaire. We used multivariable relative risk regression models to examine the association between childhood hair product use and early age at menarche (defined as

We examined beliefs about genetically targeted care (GTC) among African American men and women in a hospital-based sample and identified sociodemographic, cultural, and clinical factors having significant independent associations with these beliefs. Specifically, beliefs about GTC were evaluated after respondents were randomly primed with a racial or non-racial cue about race and genetics. Despite priming with a racial or non-racial cue, many respondents had positive beliefs about GTC. But, 49% believed that GTC would limit access to medical treatment, 46% believed that people will not trust GTC, and 20% believed that people like them would not benefit from GTC. Racial and non-racial priming did not have significant associations with negative beliefs about GTC. However, cultural beliefs related to temporal orientation were associated significantly with believing that genetically targeted care will limit access to medical treatment. Greater levels of future temporal orientation were associated with a reduced likelihood of endorsing this belief (OR = 0.70, 95% CI = 0.49, 1.01, p = 0.05). Respondents who had a chronic medical condition had an almost three-fold greater likelihood of believing that they would not benefit from GTC (OR = 2.90, 95% CI = 1.00, 8.37, p = 0.05). Greater exposure to information about genetic testing for chronic conditions was also associated with a reduced likelihood of believing that they would not benefit from GTC (OR = 0.40, 95% CI = 0.64, 0.91, p = 0.02). African Americans have diverse beliefs about GTC that should be considered as genetic and genomic services are offered.

Purpose Most studies of perceived discrimination have been cross-sectional and focused primarily on mental rather than physical health conditions. We examined the associations of perceived racial and gender discrimination reported in adulthood with early life factors and self-reported physician diagnosis of chronic physical health conditions. Methods We used data from a racially diverse birth cohort of U.S. women ( n = 168; average age, 41 years) with prospectively collected early life data (e.g., parental socioeconomic factors) and adult reported data on perceived discrimination, physical health conditions, and relevant risk factors. We performed modified robust Poisson regression owing to the high prevalence of the outcomes. Results Fifty percent of participants reported racial and 39% reported gender discrimination. Early life factors did not have strong associations with perceived discrimination. In adjusted regression models, participants reporting at least three experiences of gender or racial discrimination had a 38% increased risk of having at least one physical health condition (relative risk, 1.38; 95% confidence interval, 1.01–1.87). Using standardized regression coefficients, the magnitude of the association of having physical health condition(s) was larger for perceived discrimination than for being overweight or obese. Conclusion Our results suggest a substantial chronic disease burden associated with perceived discrimination, which may exceed the impact of established risk factors for poor physical health.

Background/Aims: Despite the investments being made to develop biobanks, African Americans are under-represented in genomic studies. We identified factors having significant independent associations with intentions to donate personal health information and blood and/or tissue samples to a biobank in a national random sample of African Americans (n = 1,033). Methods: We conducted a national survey from October 2010 through February 2011. Results: Twenty-three percent of respondents reported that it was not at all likely that they would donate to a biobank, 18% reported it was a little likely, 36% reported it was somewhat likely, and 23% reported it was very likely. Respondents who were likely to donate to a biobank had greater positive expectations about participating in cancer genetics research and reported more participation facilitators relative to barriers. Respondents who were distrustful of researchers had a significantly lower likelihood of being willing to donate to a biobank compared to those who were less distrustful. Conclusions: African Americans have diverse attitudes about participating in genetics research, and many are likely to donate to a biobank based on expectations of positive outcomes. It may be important to address attitudes about genetics research as part of recruitment to enhance the quality of informed consent for participation in biobanks among African Americans.

Moderate alcohol consumption has been linked to an approximate 30 %–50 % increased risk in breast cancer. Case-control and cohort studies have consistently observed this modest increase. We highlight recent evidence from molecular epidemiologic studies and studies of intermediate markers like mammographic density that provide additional evidence that this association is real and not solely explained by factors/correlates of the exposure and outcome present in nonrandomized studies. We also review evidence from studies of higher risk women including BRCA1 and BRCA2 mutation carriers. Given the incidence of heart disease is higher than breast cancer and modest alcohol consumption is associated with reduced risk of heart disease, we examine the latest evidence to evaluate if alcohol reduction should be targeted to women at high risk for breast cancer. We also review the most recent evidence on the effect of alcohol use on tumor recurrence and survival for those diagnosed with breast cancer.

Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care.

Aims: Scientific agencies rely on individuals to donate their DNA to support research on chronic conditions that disproportionately affect African Americans; however, donation is variable in this population. The purpose of this study was to identify sociodemographic characteristics, health care variables, and cultural values having significant independent associations with intentions to donate blood or saliva samples for cancer genetics research among African American adults. Method: Cross-sectional survey of donation intentions. Results: The majority of respondents (73%) were willing to donate a biological sample for cancer genetics research. The results of the multivariate regression model found that respondents who received care at a facility other than a doctor's office (e.g., community center) were about five times more likely to be willing to donate a sample for cancer genetics research (odds ratio [OR]=5.28, 95% confidence interval [CI]=1.16–24.12, p=0.03); whereas, greater levels of religiosity (OR=0.09, 95% CI=0.01–0.75, p=0.02) and present temporal orientation (OR=0.23, 95% CI=0.06–0.79, p=0.02) were associated with a lower likelihood of donating a sample. Conclusion: Efforts to enhance donation of biological samples for cancer genetics research may need to target diverse clinical sites for recruitment. Additionally, recruitment materials may need to address cultural values related to religiosity and present temporal orientation.

Purpose Short-term reactions to BRCA1 and BRCA2 (BRCA1/2) genetic test results have been described in several reports, but the long-terms effects of testing have not been examined extensively. Methods We conducted an observational study to characterize the long-term impact of genetic testing for BRCA1/2 mutations in 167 women who had received genetic test results at least 4 years ago. We also evaluated the relationship between genetic testing–specific reactions and breast and ovarian cancer screening to determine the behavioral significance of adverse reactions. Results Seventy-four percent of women were not experiencing any distress regarding their test result, 41% were not experiencing any uncertainty, and 51% had a score for positive experiences that was suggestive of low levels of adverse reactions in terms of family support and communication. Mutation carriers (odds ratio, 3.96; 95% CI, 1.44 to 10.89; P = .01) were most likely to experience distress. Only less time since disclosure was related significantly to experiencing uncertainty (odds ratio, 0.62; 95% CI, 0.44 to 0.88; P = .008). In terms of cancer screening, 81% of women had a mammogram during the year before study enrollment, 25% had magnetic resonance imaging (MRI), 20% had a transvaginal ultrasound, and 20% had a CA-125. Experiencing distress was associated significantly with having a CA-125 (χ2 = 3.89, P = .05), and uncertainty was associated with having an MRI (χ2 = 8.90, P = .003). Conclusion Our findings show that women are not likely to experience genetic testing concerns several years after receiving BRCA1/2 test results; distress and uncertainty are not likely to have adverse effects on screening among women at risk for hereditary disease.