The hair tales of women of color in Northern Manhattan: a qualitative analysis.

Introduction: Exposure to endocrine disrupting chemicals (EDCs), such as phthalates, can negatively impact maternal and child health, contributing to impaired fetal growth, preterm birth, and pregnancy complications, as well as increased downstream risks of cardiometabolic disease and breast cancer. Notably, women of color (WOC) are the largest consumers of personal care products, which are a common source of EDC exposure. Methods: The Let's Reclaim Our Ancestral Roots (Let's R.O.A.R) Pilot Study developed an educational intervention delivered during pregnancy to promote reduced use of phthalate-containing hair care products (HCPs). This mixed-methods study included: (1) a quantitative analysis and (2) a qualitative analysis of the educational sessions and the semi-structured focus groups to evaluate the factors that influenced the hair care practices and product choices of WOC at various stages of life, including their current pregnancy (hereafter referred to as the hair journey). During the sessions, participants learned about EDCs (with a focus on phthalates), the unequal burden of exposure for WOC, adverse implications of exposure, and exposure reduction strategies. Focus group sessions provided insight into participants' hair journeys from childhood to the current pregnancy and explored factors during their hair product selection process. All sessions were transcribed and imported into NVivo Version 12 for coding and thematic analysis. Results: A total of 46 individuals were enrolled in the study, and 31 participated in an educational session. This current work synthesizes the qualitative analysis of this study. We identified two important life stages (before and after gaining agency over hair care practices and product choices) and three dominant themes related to HCP use: (1) products that impacted the hair journey, which involved all mentions of hair products, (2) factors that influenced the hair journey, which included individuals or entities that shaped participants' hair experiences, and (3) the relationship between hair and sense of self, where sense of self was defined as the alignment of one's inner and outer beauty. Conclusion: The themes intersected and impacted the participants' hair journey. Cultural integration was a sub-theme that overlapped within the dominant themes and participants discussed the effect of traditions on their hair experiences.

Childhood physical activity and pubertal timing: findings from the LEGACY girls study.

BACKGROUND: There is limited research on whether physical activity (PA) in early childhood is associated with the timing of pubertal events in girls. METHODS: We used data collected over 2011-16 from the LEGACY Girls Study (n = 984; primarily aged 6-13 years at study enrolment), a multicentre North American cohort enriched for girls with a breast cancer family history (BCFH), to evaluate if PA is associated with age at thelarche, pubarche and menarche. Maternal-reported questionnaire data measured puberty outcomes, PA in early childhood (ages 3-5 years) and total metabolic equivalents of organized PA in middle childhood (ages 7-9 years). We used interval-censored Weibull parametric survival regression models with age as the time scale and adjusted for sociodemographic factors, and we tested for effect modification by BCFH. We used inverse odds weighting to test for mediation by body mass index-for-age z-score (BMIZ) measured at study enrolment. RESULTS: Being highly active vs inactive in early childhood was associated with later thelarche in girls with a BCFH [adjusted hazard ratio (aHR) = 0.39, 95% CI = 0.26-0.59), but not in girls without a BCFH. In all girls, irrespective of BCFH, being in the highest vs lowest quartile of organized PA in middle childhood was associated with later menarche (aHR = 0.70, 95% CI = 0.50-0.97). These associations remained after accounting for potential mediation by BMIZ. CONCLUSION: This study provides new data that PA in early childhood may be associated with later thelarche in girls with a BCFH, also further supporting an overall association between PA in middle childhood and later menarche.

Maternal and prenatal factors and age at thelarche in the LEGACY Girls Study cohort: implications for breast cancer risk.

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 <25 and gained <30 lbs [hazard ratio (HR) = 1.57, 95% CI: 1.16, 2.12]. This association was not mediated by childhood BMI and was similar in girls with and without a BCFH (BCFH: HR = 1.41, 95% CI: 0.87, 2.27; No BCFH: HR = 1.62, 95% CI: 1.10, 2.40). Daughters of women who reported no recreational physical activity during pregnancy were more likely to experience earlier thelarche compared with daughters of physically active women. Birthweight and birth length were not associated with thelarche. 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.

Body mass index rebound and pubertal timing in girls with and without a family history of breast cancer: the LEGACY girls study.

BACKGROUND: Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty. METHODS: In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models. RESULTS: The median age at BMI rebound was 5.3 years (interquartile range: 3.6-6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83-0.97) and menarche (HR = 0.86; 95% CI = 0.79-0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development. CONCLUSIONS: Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk.

"Mother's Health and Well-Being Matters: Is a Mediated Social Cohesion Public Health Intervention Feasible?"

PURPOSE: To test the feasibility of introducing 'Free Time for Wellness' (FT4W) an intervention to increase healthy behaviours and reduce the risk of cancer. DESIGN: Feasibility study; Setting: Washington Heights, New York, USA is a low socioeconomic status area. SUBJECTS: Mothers aged 18 and above with children under 12 years of age and living in Washington Heights were recruited. INTERVENTION: FT4W, a community-based intervention delivered through a neighbourhood-based app, offering weekly dance and yoga classes, food pantry visits and group playdates. Childcare professionals cared for participants' children during wellness activities. MEASURES: A bespoke before and after survey was designed and tested for its ability to collect relevant data to assess the impact of FT4W. Outcomes included recruitment rates, participation, attrition, acceptability, and success of the community champion. ANALYSIS: Comparisons of proportions and means. RESULTS: Twenty-one mothers participated in the study of which 90% attended ≥ 1 FT4W activity; 65% ≥ 2; 52% ≥ 3. The survey was completed by a 100% of participants indicating it was easy to understand and not too burdensome. All measures detected change in constructs from baseline to follow-up. Availability of childcare was the most commonly (66%) reported reason participants were able to engage in the offered wellness activities. CONCLUSION: Conducting a larger-scale trial to assess the impact of FT4W is feasible considering 4 major lessons. (1) Recruitment, retention, and acceptability rates were high; however, moms need additional support to increase participation in wellness activities and improve tech literacy. (2) Research measures were sensitive enough to detect change, but the timing of assessments needs to be considered. (3) Participants greatly valued access to professional childcare. (4) The Community Champion is a necessary, but difficult role to fill that requires careful consideration by the Institutional Review Board (IRB).

Free Time For Wellness: a co-designed intervention utilizing social networks to encourage physical activity for cancer prevention among low resourced mothers.

BACKGROUND: Physical activity is central to chronic disease prevention. Low resource mothers face structural barriers preventing them from increasing their physical activity to reduce their chronic disease risk. We co-designed an intervention, with the ultimate goal of building social cohesion through social media to increase physical activity for low resourced mothers in urban settings. METHODS: In 2019, we interviewed 10 mothers of children (< 12 years) living in Washington Heights, Manhattan. The interviews were transcribed and coded for themes that guided the creation of a co-design workshop. Washington Heights-based mothers (n = 16) attended a co-design workshop to generate the blueprint for the Free Time for Wellness intervention. RESULTS: Mothers in our sample had limited time, external support and resources, which hindered them from increasing their physical activity; we learned that in addition to physical health, mental health was a concern for participants. Participants had varying degrees of self-efficacy and trust in social media. Bringing mothers and researchers together in a co-design workshop, we identified types of physical activities they would enjoy participating in, the ideal time to do so, the kind of childcare they needed, and their preferences for communication with the community champion. The interviews and workshop highlighted the need for a community space that mothers and children could co-occupy. The intervention was designed to be 3 months' worth of sample programming with one activity per week, rotating between dance, yoga, food pantry visits and group playdates. Participants were invited to bring their children to a space with one room for the 'participants only' activity and a second room in which professional childcare providers supervised the children. CONCLUSIONS: Through this two-phased co-design process, we created an intervention with mothers in an urban community with the goal of using social media to bring them together for wellness, primarily through increased physical activity. Despite the co-design of this intervention with a specific community, there are some universal applications of our findings, and of the use of co-design workshops, to other settings.

Use of Social Media for Cancer Prevention Through Neighborhood Social Cohesion: Protocol for a Feasibility Study.

BACKGROUND: Social cohesion is associated with healthier behaviors and better health outcomes, and therefore may offer a mechanism for promoting better health. Low socioeconomic status (SES) communities face higher rates of chronic disease due to both community- and individual-level factors. OBJECTIVE: The aim of this study is to leverage social cohesion to promote healthier behaviors and prevent chronic disease in a low SES community. This protocol outlines the methodology for a pilot study to assess the feasibility of an intervention (Free Time For Wellness [FT4W]) using a social networking platform (Nextdoor) with mothers living in an urban, low-income community to improve social cohesion and promote healthy behaviors. METHODS: The study will involve three phases: (I) co-designing the intervention with mothers in the neighborhoods of interest, (II) implementing the intervention with community leaders through the social networking platform, and (III) evaluating the intervention's feasibility. Phase I of the study will include qualitative data collection and analysis from in-depth, semistructured interviews and a co-design group session with mothers. Phases II and III of the study include a pre- and postintervention survey of participating mothers. Neighborhood-level data on social cohesion will also be collected to enable comparison of outcomes between neighborhoods with higher and lower baseline social cohesion. RESULTS: As of March 2021, recruitment and data collection for this study are complete. This protocol outlines our original study plan, although the final enrollment numbers and intervention implementation deviated from our initial planned methodology that is outlined in this protocol. These implementation learnings will be shared in subsequent publications of our study results. CONCLUSIONS: Ultimately, this study aims to: (1) determine the barriers and facilitators to finding free time for wellness among a population of low-income mothers to inform the co-design process, and (2) implement and study the feasibility of an intervention that leverages social cohesion to promote physical activity in a community of low-income mothers. The results of this study will provide preliminary feasibility evidence to inform a larger effectiveness trial, and will further our understanding of how social cohesion might influence well-being. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/28147.

The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids.

BACKGROUND: No study has comprehensively examined how the steroid metabolome is associated with breast cancer risk in women with familial risk. METHODS: We examined 36 steroid metabolites across the spectrum of familial risk (5-year risk ranged from 0.14% to 23.8%) in pre- and postmenopausal women participating in the New York site of the Breast Cancer Family Registry (BCFR). We conducted a nested case-control study with 62 cases/124 controls individually matched on menopausal status, age, and race. We measured metabolites using GC-MS in urine samples collected at baseline before the onset of prospectively ascertained cases. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) per doubling in hormone levels. RESULTS: The average proportion of total steroid metabolites in the study sample were glucocorticoids (61%), androgens (26%), progestogens (11%), and estrogens (2%). A doubling in glucocorticoids (aOR = 2.7; 95% CI = 1.3-5.3) and androgens (aOR = 1.6; 95% CI = 1.0-2.7) was associated with increased breast cancer risk. Specific glucocorticoids (THE, THF αTHF, 6ß-OH-F, THA, and α-THB) were associated with 49% to 161% increased risk. Two androgen metabolites (AN and 11-OH-AN) were associated with 70% (aOR = 1.7; 95% CI = 1.1-2.7) and 90% (aOR = 1.9; 95% CI = 1.2-3.1) increased risk, respectively. One intermediate metabolite of a cortisol precursor (THS) was associated with 65% (OR = 1.65; 95% CI = 1.0-2.7) increased risk. E1 and E2 estrogens were associated with 20% and 27% decreased risk, respectively. CONCLUSIONS: Results suggest that glucocorticoids and 11-oxygenated androgens are positively associated with breast cancer risk across the familial risk spectrum. IMPACT: If replicated, our findings suggest great potential of including steroids into existing breast cancer risk assessment tools.

Prepubertal Internalizing Symptoms and Timing of Puberty Onset in Girls.

Stressful environments have been associated with earlier menarche. We hypothesized that anxiety, and possibly other internalizing symptoms, are also associated with earlier puberty in girls. The Lessons in Epidemiology and Genetics of Adult Cancer From Youth (LEGACY) Girls Study (2011-2016) included 1,040 girls aged 6-13 years at recruitment whose growth and development were assessed every 6 months. Prepubertal maternal reports of daughter's internalizing symptoms were available for breast onset (n = 447), pubic hair onset (n = 456), and menarche (n = 681). Using Cox proportional hazard regression, we estimated prospective hazard ratios and 95% confidence intervals for the relationship between 1 standard deviation of the percentiles of prepubertal anxiety, depression, and somatization symptoms and the timing of each pubertal outcome. Multivariable models included age, race/ethnicity, study center, maternal education, body mass index percentile, and family history of breast cancer. Additional models included maternal self-reported anxiety. A 1-standard deviation increase in maternally reported anxiety in girls at baseline was associated with earlier subsequent onset of breast (hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.09, 1.36) and pubic hair (HR = 1.15, 95% CI: 1.01, 1.30) development, but not menarche (HR = 0.94, 95% CI: 0.83, 1.07). The association of anxiety with earlier breast development persisted after adjustment for maternal anxiety. Increased anxiety in young girls may indicate risk for earlier pubertal onset.

Assessing Endogenous and Exogenous Hormone Exposures and Breast Development in a Migrant Study of Bangladeshi and British Girls.

Timing of breast development (or thelarche) and its endogenous and exogenous determinants may underlie global variation in breast cancer incidence. The study objectives were to characterize endogenous estrogen levels and bisphenol A (BPA) exposure using a migrant study of adolescent girls and test whether concentrations explained differences in thelarche by birthplace and growth environment. Estrogen metabolites (EM) and BPA-glucuronide (BPA-G) were quantified in urine spot samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) from a cross-sectional study of Bangladeshi, first- and second-generation Bangladeshi migrants to the UK, and white British girls aged 5-16 years (n = 348). Thelarche status at the time of interview was self-reported and defined equivalent to Tanner Stage ≥2. We compared geometric means (and 95% confidence interval (CIs)) of EM and BPA-G using linear regression and assessed whether EM and BPA-G explained any of the association between exposure to the UK and the age at thelarche using hazard ratios and 95% confidence intervals. Average EM decreased with exposure to the UK, whereas BPA-G increased and was significantly higher among white British (0.007 ng/mL, 95% CI: 0.0024-0.0217) and second-generation British-Bangladeshi girls (0.009 ng/mL, 95% CI: 0.0040-0.0187) compared to Bangladeshi girls (0.002 ng/mL, 95% CI: 0.0018-0.0034). Two of four EM ratios (16-pathway/parent and parent/all pathways) were significantly associated with thelarche. The relationship between exposure to the UK and thelarche did not change appreciably after adding EM and BPA-G to the models. While BPA-G is often considered a ubiquitous exposure, our findings suggest it can vary based on birthplace and growth environment, with increasing levels for girls who were born in or moved to the UK. Our study did not provide statistically significant evidence that BPA-G or EM concentrations explained earlier thelarche among girls who were born or raised in the UK.

Risk of Prostate Cancer-related Death Following a Low PSA Level in the PLCO Trial.

Longer-than-annual screening intervals have been suggested to improve the balance of benefits and harms in prostate cancer screening. Many researchers, societies, and guideline committees have suggested that screening intervals could depend on the prostate-specific antigen (PSA) result. We analyzed data from men (N = 33,897) ages 55-74 years with a baseline PSA test in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial (United States, 1993-2001). We estimated 5- and 10-year risks of aggressive cancer (Gleason ≥8 and/or stage III/IV) and 15-year risks of prostate cancer-related mortality for men with baseline PSA ≤ 0.5 ng/mL (N = 4,862), ≤1 ng/mL (N = 15,110), and 1.01-2.5 ng/mL (N = 12,422). A total of 217 men died from prostate cancer through 15 years, although no men with PSA ≤ 1 ng/mL died from prostate cancer within 5 years [95% confidence interval (CI), 0.00%-0.03%]. The 5-year incidence of aggressive disease was low (0.08%; 95% CI, 0.03%-0.12%) for men with PSA ≤ 1 ng/mL, and higher for men with baseline PSA 1.01-2.5 ng/mL (0.51%; 95% CI, 0.38%-0.74%). No men aged ≥65 years with PSA ≤ 0.5 ng/mL died from prostate cancer within 15 years (95% CI, 0.00%-0.32%), and their 10-year incidence of aggressive disease was low (0.25%; 95% CI, 0.00%-0.53%). Compared with white men, black men with PSA ≤ 1 ng/mL had higher 10-year rates of aggressive disease (1.6% vs. 0.4%; P < 0.01). Five-year screening intervals may be appropriate for the 45% of men with PSA ≤ 1 ng/mL. Men ages ≥65 years with PSA ≤ 0.5 ng/mL could consider stopping screening. Substantial risk disparities suggest appropriate screening intervals could depend on race/ethnicity.

Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND: Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS: From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS: The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS: Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

Mobilizing Breast Cancer Prevention Research Through Smartphone Apps: A Systematic Review of the Literature.

Background: Breast cancer rates have been increasing worldwide, particularly among young women, suggesting important interactions between genes and health behaviors. At the same time, mobile technology, including smartphones applications (apps), has emerged as a new tool for delivering healthcare and health-related services. As of 2018, there were nearly 600 publicly available breast cancer apps designed to provide disease and treatment information, to manage disease, and to raise overall awareness. However, the extent to which apps are incorporated into breast cancer prevention research is unknown. Therefore, the objective of this review was to determine how mobile applications are being used for breast cancer prevention among women across the cancer control continuum. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and Web of Science Core Collection databases using the keywords breast cancer, smartphone, mobile application, and phone app. Full-length journal articles available in English that addressed the research question were included. We categorized articles by prevention type (primary, secondary, and tertiary) and phase of research (protocol, development, feasibility, pilot, measurement, and effectiveness), and identified common themes and gaps. Results: Our search yielded 82 studies (69 unique) that used apps in breast cancer prevention research across 20 countries. Approximately half of the named apps were publicly available. The majority (73%) of studies targeted tertiary prevention; 15% targeted secondary and 13% targeted primary prevention. Apps were used across all phases of research with the predominant phase being feasibility in tertiary prevention (34%), effectiveness in secondary prevention (63%), and development (30%) and effectiveness (30%) in primary prevention. Common uses included assessing outcomes relevant to clinical care coordination, quality of life, increasing self-efficacy and screening behaviors, and tracking and managing health behaviors. Conclusions: We identified the following gaps: few effectiveness studies in tertiary prevention, minimal use of apps for breast cancer etiology or early detection, and few interventions in those at average risk of breast cancer. These findings suggest that while mobile apps can inform breast cancer prevention across the continuum, more work is needed to incorporate apps into primary prevention.

Early-Life Growth and Benign Breast Disease.

Using prospective data from the Early Determinants of Mammographic Density study (United States, 1959-2008, n = 1121), we examined the associations between maternal body size, birth size, and infant and early childhood growth during 3 time periods (0-4 months, 4-12 months, and 1-4 years) and benign breast disease (BBD) using multivariable logistic regression with generalized estimating equations. A total of 197 women (17.6%) reported receiving a diagnosis of BBD by a physician. Higher body mass index at age 7 years was inversely associated with BBD risk. Rapid weight gain from age 1 year to 4 years, defined as an increase of least 2 major percentiles (e.g., 5th, 10th, 25th, 50th, 75th, and 95th) relative to stable growth, defined as remaining within 2 percentiles, was also inversely associated with BBD (odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.23, 1.15). In contrast, rapid weight gain in infancy was positively associated with BBD relative to stable growth (from 0 to 4 months, OR = 1.65, 95% CI: 1.04, 2.62; from 4 to 12 months, 1.85, 95% CI: 0.89, 3.85), independent of birth weight, which was not associated with BBD. Our results suggest that patterns of early-life weight gain are important to BBD risk. Thus, susceptibility to BBD, like susceptibility to breast cancer, might start in early life.

Association of Prepubertal and Adolescent Androgen Concentrations With Timing of Breast Development and Family History of Breast Cancer.

Importance: Early breast development is a risk factor for breast cancer, and girls with a breast cancer family history (BCFH) experience breast development earlier than girls without a BCFH. Objectives: To assess whether prepubertal androgen concentrations are associated with timing of breast development (analysis 1) and to compare serum androgen concentrations in girls with and without a BCFH (analysis 2). Design, Setting, and Participants: Prospective cohort study of 104 girls aged 6 to 13 years at baseline using data collected between August 16, 2011, and March 24, 2016, from the Lessons in Epidemiology and Genetics of Adult Cancer From Youth (LEGACY) Girls Study, New York site. Exposures: Analysis 1 included serum concentrations of dehydroepiandrosterone sulfate, androstenedione, and testosterone (free and total) measured before breast development and divided at the median into high and low categories. Analysis 2 included the degree of BCFH: first-degree was defined as having a mother with breast cancer and second-degree was defined as having a grandmother or aunt with breast cancer. Main Outcomes and Measures: Analysis 1 included age at onset of breast development measured using the Pubertal Development Scale (scores range from 1-4; scores ≥2 indicate breast development), and analysis 2 included serum androgen concentrations. We also assessed breast cancer-specific distress using the 8-item Child Impact of Events Scale. Results: Our analyses included 36 girls for the prospective model, 92 girls for the cross-sectional model, and 104 girls for the longitudinal model. Of the 104 girls, the mean (SD) age at baseline was 10.3 (2.5) years, and 41 (39.4%) were non-Hispanic white, 41 (39.4%) were Hispanic, 13 (12.5%) were non-Hispanic black, and 9 (8.7%) were other race/ethnicity. Forty-two girls (40.4%) had a positive BCFH. Girls with prepubertal androstenedione concentrations above the median began breast development 1.5 years earlier than girls with concentrations below the median (Weibull survival model-estimated median age, 9.4 [95% CI, 9.0-9.8] years vs 10.9 [95% CI, 10.4-11.5] years; P = .001). Similar patterns were observed for dehydroepiandrosterone sulfate (1.1 years earlier: age, 9.6 [95% CI, 9.1-10.1] years vs 10.7 [95% CI, 10.2-11.3] years; P = .009), total testosterone (1.4 years earlier: age, 9.5 [95% CI, 9.1-9.9] years vs 10.9 [95% CI, 10.4-11.5] years; P = .001), and free testosterone (1.1 years earlier: age, 9.7 [95% CI, 9.2-10.1] years vs 10.8 [95% CI, 10.2-11.4] years; P = .01). Compared with girls without BCFH, girls with a first-degree BCFH, but not a second-degree BCFH, had 240% higher androstenedione concentrations (geometric means: no BCFH, 0.49 ng/mL vs first-degree BCFH, 1.8 ng/mL vs second-degree, 1.6 ng/mL; P = .01), 10% higher total testosterone concentrations (12.7 ng/dL vs 14.0 ng/dL vs 13.7 ng/dL; P = .01), and 92% higher free testosterone concentrations (1.3 pg/mL vs 2.5 pg/mL vs 0.3 pg/mL; P = .14). The dehydroepiandrosterone sulfate concentration did not differ between BCFH-positive and BCFH-negative girls but was elevated in girls with breast cancer-specific distress. Conclusions and Relevance: Our findings suggest that androgen concentrations may differ between girls with and without a BCFH and that elevated hormone concentrations during adolescence may be another factor to help explain the familial clustering of breast cancer.

Do Birth Weight and Weight Gain During Infancy and Early Childhood Explain Variation in Mammographic Density in Women in Midlife? Results From Cohort and Sibling Analyses.

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, ß = 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, ß = -0.65, 95% CI: -1.23, -0.07, and ß = -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.

Comparison of methods to assess onset of breast development in the LEGACY Girls Study: methodological considerations for studies of breast cancer.

BACKGROUND: Younger age at onset of breast development, which has been declining in recent decades, is associated with increased breast cancer risk independent of age at menarche. Given the need to study the drivers of these trends, it is essential to validate methods to assess breast onset that can be used in large-scale studies when direct clinical assessment of breast onset is not feasible. METHODS: Breast development is usually measured by Tanner stages (TSs), assessed either by physical examination or by mother's report using a picture-based Sexual Maturation Scale (SMS). As an alternative, a mother-reported Pubertal Development Scale (PDS) without pictures has been used in some studies. We compared agreement of SMS and PDS with each other (n = 1022) and the accuracy of PDS with clinical TS as a gold standard for the subset of girls with this measure (n = 282) using the LEGACY cohort. We further compared prediction of breast onset using ROC curves and tested whether adding urinary estrone 1-glucuronide (E1G) improved the AUC. RESULTS: The agreement of PDS with SMS was high (kappa = 0.80). The sensitivity of PDS vs clinical TS was 86.6%. The AUCs for PDS alone and SMS alone were 0.88 and 0.79, respectively. Including E1G concentrations improved the AUC for both methods (0.91 and 0.86 for PDS and SMS, respectively). CONCLUSIONS: The PDS without pictures is a highly accurate, sensitive, and specific method for assessing breast onset, especially in settings where clinical TS is not feasible. In addition, it is comparable to SMS methods with pictures and thus easier to implement in large-scale studies, particularly phone-based interviews where pictures may not be available. Urinary E1G can improve accuracy over than PDS or SMS alone.

Estrogen Metabolism in Premenopausal Women Is Related to Early Life Body Fatness.

Background: Estrogen metabolism in premenopausal women may be related to early life body fatness.Methods: Premenopausal women participating in the Nurses' Health Study II recalled their body fatness at ages 5, 10, and 20 years using a validated 9-level pictogram. Fifteen estrogens and estrogen metabolites (EM) were measured using LC/MS-MS in luteal phase urines from 603 women ages 32-54 years. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by body fatness categories using linear mixed models.Results: Body fatness at each age was inversely associated with adult concentrations of all EM combined, parent estrogens (estrone, estradiol), and the 2-hydroxylation pathway. Women in the top (vs. bottom) category of body fatness at age 10 had 21% lower levels of all EM (Ptrend = 0.003), 24% lower parent estrogens (Ptrend = 0.002), and 36% lower 2-pathway (Ptrend = 0.0003). Body fatness at age 10 was inversely associated with 2-catechols (35% lower, Ptrend = 0.0004) and 2-methylated catechols (30% lower, Ptrend = 0.002). After adjusting for premenopausal body mass index (BMI), these associations remained inverse but were attenuated; only parent estrogens remained statistically significant (21% lower, Ptrend = 0.01). Body fatness at ages 5 and 20 were similarly, but more weakly, associated with estrogen pathways.Conclusions: Estimates of body fatness during early life were inversely associated with premenopausal levels of all EM combined, parent estrogens, and 2-pathway estrogen metabolites. These relationships were not fully explained by adult BMI.Impact: These findings inform investigations of diseases linked to early life body fatness and estrogen metabolism. Cancer Epidemiol Biomarkers Prev; 27(5); 585-93. ©2018 AACR.

Why do studies show different associations between intrauterine exposure to maternal smoking and age at menarche?

PURPOSE: Studies suggests that intrauterine exposure to maternal smoking both accelerates or delays age at menarche. We hypothesize that these opposing findings relate to different infant and childhood growth patterns across cohorts. METHODS: Using data from an adult follow-up study of the Child Health and Development Studies and the National Collaborative Perinatal Project, we examined, using generalized estimating linear regression models, whether intrauterine exposure to maternal smoking was associated with age at menarche in 1090 daughters before and after accounting for growth in weight. RESULTS: Compared to the nonexposed, intrauterine exposure to maternal smoking was associated with a 4-month acceleration in menarche in the National Collaborative Perinatal Project (ß = -0.35 years; 95% confidence interval [CI]: -0.63, -0.08), but a 6-month delay in menarche in the Child Health and Development Studies (ß = 0.48 years; 95% CI: 0.13, 0.83), despite having a similar reduction in birth weight in both cohorts (∼300 g). The results were more consistent across cohorts when we stratified by postnatal growth patterns. For example, in those with rapid weight gain (increasing two growth references from 0 to 4 years), intrauterine exposure to maternal smoking was related to a 7-month acceleration in menarche (ß = -0.56 years; 95% CI: -0.95, -0.17). CONCLUSIONS: These findings suggest that the association of intrauterine exposure to maternal smoking on age at menarche depends on postnatal growth patterns.

Pubertal development in girls by breast cancer family history: the LEGACY girls cohort.

BACKGROUND: Pubertal milestones, such as onset of breast development and menstruation, play an important role in breast cancer etiology. It is unclear if these milestones are different in girls with a first- or second-degree breast cancer family history (BCFH). METHODS: In the LEGACY Girls Study (n = 1040), we examined whether three mother/guardian-reported pubertal milestones (having reached Tanner Stage 2 or higher (T2+) for breast and pubic hair development, and having started menstruation) differed by BCFH. We also examined whether associations between body size and race/ethnicity and pubertal milestones were modified by BCFH. We used mother/guardian reports as the primary measure of pubertal milestones, but also conducted sensitivity analyses using clinical Tanner measurements available for a subcohort (n = 204). We analyzed cross-sectional baseline data with logistic regression models for the entire cohort, and longitudinal data with Weibull survival models for the subcohort of girls that were aged 5-7 years at baseline (n = 258). RESULTS: BCFH was modestly, but not statistically significantly, associated with Breast T2+ (odds ratio (OR) = 1.36, 95% confidence interval (CI) = 0.88-2.10), with a stronger association seen in the subcohort of girls with clinical breast Tanner staging (OR = 2.20, 95% CI = 0.91-5.32). In a longitudinal analysis of girls who were aged 5-7 years at baseline, BCFH was associated with a 50% increased rate of having early breast development (hazard ratio (HR) = 1.49, 95% CI = 1.0-2.21). This association increased to twofold in girls who were not overweight at baseline (HR = 2.04, 95% CI = 1.29-3.21). BCFH was not associated with pubic hair development and post-menarche status. The median interval between onset of breast development and menarche was longer for BCFH+ than BCFH- girls (2.3 versus 1.7 years), suggesting a slower developmental tempo for BCFH+ girls. Associations between pubertal milestones and body size and race/ethnicity were similar in girls with or without a BCFH. For example, weight was positively associated with Breast T2+ in both girls with (OR = 1.06 per 1 kg, 95% CI = 1.03-1.10) and without (OR = 1.14 per 1 kg, 95% CI = 1.04-1.24) a BCFH. CONCLUSIONS: These results suggest that BCFH may be related to earlier breast development and slower pubertal tempo independent of body size and race/ethnicity.