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Purpose: Clinical trial enrollment is low among adolescents and young adults (AYAs) with cancer and may contribute to inferior survival gains in recent years in this population compared with other age groups. We investigated clinical trial participation among AYA women with cancer, and examined whether patients discussed clinical trial participation with their doctor and reasons for nonparticipation. Methods: Women with a diagnosis of breast cancer, thyroid cancer, melanoma, lymphoma, or gynecologic cancer at ages 15-39 years during 2004-2016 were identified from the North Carolina Central Cancer Registry and the Kaiser Permanente Southern California health system. During 2018-2019, a total of 1264 eligible women completed an online survey (response = 13%), which examined survivorship issues among AYAs. Results: Overall, 5% of participants reported that they had participated in a clinical trial. Most women reported that they had not discussed clinical trial participation with a medical provider (76%) and that they did not know whether a relevant trial was available for their cancer (73%). Among those who knew that a trial was available but did not participate, the most commonly reported reasons for nonparticipation included concerns about side effects of the treatment in the trial and concerns that the treatment had not been sufficiently tested. Conclusion: Only a small proportion of AYA women with cancer in our cohort reported discussing a clinical trial with a provider or knowing whether a relevant trial was available. Our findings point to opportunities to improve patient/provider communication to increase clinical trial enrollment among AYAs with cancer.

Background: Population-based cancer registries collect information on first course of treatment that may be utilized in research on cancer care quality, yet few studies have investigated the validity of this information. We examined the accuracy and completeness of registry-based treatment information in a cohort of adolescent and young adult women., Methods: Women diagnosed with breast cancer, lymphoma, thyroid cancer, cervical/uterine cancer or ovarian cancer at ages 15-39 during 2003-2014 were identified using data from the North Carolina Central Cancer Registry (CCR) (N = 2342). CCR data were linked to Medicaid and private insurance claims data, and claims were reviewed for the 12 months following diagnosis to identify cancer treatments received. Using claims data as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of CCR data for receipt of chemotherapy, radiation and hormone therapy. We also compared dates of treatment initiation between the two data sources., Results: For all cancer types combined, the sensitivity of the CCR data was high for chemotherapy (86%) and moderate for radiation (74%). PPVs were 82% and 83% for chemotherapy and radiation, respectively. Both the sensitivity (67%) and PPV (70%) were lower for hormone therapy for breast cancer. For all three treatment types, dates of initiation in the registry and the claims differed by ≤30 days for most women., Conclusions: In this cohort of young women, population-based cancer registry data on chemotherapy receipt was reasonably accurate and complete in comparison with insurance claims. Radiation and hormone therapy appeared to be less complete., Competing Interests: Declarations of Competing Interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Tamoxifen and raloxifene have been approved for the primary prevention of breast cancer in high-risk women, but are associated with an increased risk of serious side effects. Few studies have characterized risk-benefit profiles for chemoprevention among women who initiate tamoxifen or raloxifene outside of a clinical trial setting. Use of raloxifene and tamoxifen for chemoprevention was self-reported in 2014 to 2016 by participants in The Sister Study, a prospective cohort of women with a sister who had been diagnosed with breast cancer. After exclusions, 432 current raloxifene users and 96 current tamoxifen users were matched to 4,307 and 953 nonusers, respectively, on age and year of cohort enrollment. Conditional logistic regression was used to evaluate characteristics associated with chemoprevention use. Risk-benefit profiles were examined using published indices that assess the level of evidence (none, moderate, strong) that the benefits of chemoprevention outweigh the risk of serious side effects. Among current chemoprevention users, 44% of tamoxifen users and 5% of raloxifene users had no evidence of a net benefit. In analyses of factors associated with chemoprevention use, having strong evidence of benefit was a significant predictor of raloxifene use, but not of tamoxifen use. In our sample of women with a first-degree family history of breast cancer, raloxifene was more commonly used for breast cancer prevention than tamoxifen. Most raloxifene users, but <60% of tamoxifen users, were likely to benefit. Use of risk-benefit tables can help women and their healthcare providers make an informed decision about breast cancer chemoprevention., (©2019 American Association for Cancer Research.)

Study Question: Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age?, Summary Answer: Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age., What Is Known Already: A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies., Study Design, Size, Duration: We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort., Participants/materials, Setting, Methods: Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association β-values and 95% CIs using linear regression., Main Results and the Role of Chance: All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: β = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: β = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: β = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (β = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (β = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7)., Limitations, Reasons for Caution: We relied on retrospective recall to ascertain reproductive history and pregnancy complications., Wider Implications of the Findings: Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome., Study Funding/competing Interest(s): This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest., Trial Registration Number: Not applicable., (Published by Oxford University Press 2019.)

Background High levels of physical activity have been associated with longer life expectancy free of cardiovascular disease (CVD), but specific types of CVD and sedentary behavior have not been examined. We examined associations of leisure-time moderate-to-vigorous physical activity (LTPA) and television viewing with life expectancy free of 3 types of CVD. Methods and Results We included 13 534 participants from the ARIC (Atherosclerosis Risk in Communities) cohort. We used multistate survival models to estimate associations of LTPA in the past year (no LTPA, less than the median, equal to or greater than the median) and television viewing (often or very often, sometimes, seldom or rarely) with life expectancy at age 50 free of nonfatal coronary heart disease (CHD), stroke, and heart failure (HF). Over 27 years of follow-up, 4519 participants developed one of the 3 nonfatal CVDs and 5475 deaths occurred. Compared with participants who engaged in no LTPA, participants who engaged in LTPA equal to or greater than the median had longer life expectancy free of nonfatal CHD (men: 1.5 years [95% CI, 1.0-2.0]; women: 1.6 years [95% CI, 1.1-2.2]), stroke (men: 1.8 years [95% CI, 1.2-2.3]; women: 1.8 years [95% CI, 1.3-2.3]), and HF (men: 1.6 years [95% CI, 1.1-2.1]; women: 1.7 years [95% CI, 1.2-2.2]). Compared with viewing more television, watching less television was associated with longer life expectancy free of CHD, stroke, and HF (≈0.8 year). Conclusions Higher levels of LTPA and less television viewing were associated with longer life expectancy free of CHD, stroke, and HF. Engaging in LTPA and watching less television may increase the number of years lived free of CHD, stroke, and HF.

Introduction: Potentially carcinogenic hazardous air pollutants (air toxics) have been inconsistently associated with breast cancer. Whether metabolic factors modify these associations is unknown. We studied 29 non-metallic air toxics classified as mammary gland carcinogens in animal studies in relation to breast cancer risk., Methods: Participants included 49,718 women from the Sister Study. Census tract air toxic concentration estimates from the 2005 National Air Toxics Assessment were linked to enrollment residential addresses. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for individual air toxics were estimated using Cox regression. Body mass index (BMI) was considered a potential modifier. Relevant mixtures were identified using classification trees., Results: Over follow-up (average = 8.4 years), 2975 women were newly diagnosed with breast cancer (invasive or ductal carcinoma in situ). Several air toxics, including methylene chloride, polycyclic organic matter, propylene dichloride, and styrene, were associated with increased risk. Of these, methylene chloride was most consistently associated with risk across multiple analyses. It was associated with overall (HR quintile 4vs1  = 1.21 (95%CI = 1.07-1.38)) and estrogen receptor positive (ER+) invasive breast cancer (HR quintile 4vs1  = 1.28 (95%CI = 1.08-1.52)) in individual pollutant models, although no dose-response was observed. Associations were stronger among overweight/obese (vs. non-overweight/obese) women (p < 0.05) for six air toxics. The classification tree identified combinations of age, methylene chloride, BMI, and four other toxics (propylene dichloride, ethylene dibromide, ethylidene dichloride, styrene) related to overall breast cancer., Conclusions: Some non-metallic air toxics, particularly methylene chloride, were associated with the hazard for overall and ER+ breast cancer. Overweight/obese women may be particularly susceptible to air toxics., (Published by Elsevier Ltd.)

Background: Few studies have examined noncancer outcomes among patients diagnosed with cancer as adolescents and young adults (AYA). We examined risk of mortality from noncancer causes after an AYA cancer diagnosis and investigated disparities according to race/ethnicity and other characteristics., Methods: Patients with a first primary cancer at ages 15 to 39 years diagnosed during 1987 to 2015 were identified in the Surveillance, Epidemiology, and End Results database ( N = 242,940 women, 158,347 men). Survival months were accrued from diagnosis until death or December 2015. Multivariable-adjusted HRs were used to examine disparities in mortality from all noncancer causes, cardiovascular diseases (CVD), and infectious diseases (ID) according to race/ethnicity, geographic region, and county-level characteristics., Results: For all cancer types combined, the 10-year cumulative incidence of noncancer-related death after AYA cancer was 2% and 5% among women and men, respectively. With adjustment for cancer type, all noncancer mortality was increased among non-Hispanic Black AYAs [HR vs. non-Hispanic White: HR Women = 2.31; 95% confidence interval (CI): 2.16-2.47; HR Men = 2.17; 95% CI: 2.05-2.30] and those in the South (HR vs. Northeast: HR Women = 1.18; 95% CI: 1.07-1.29; HR Men = 1.42; 95% CI: 1.31-1.55) or in rural counties (HR vs. metro: HR Women = 1.74; 95% CI: 1.47-2.07; HR Men = 1.57; 95% CI: 1.33-1.86). Mortality from CVD and ID was also elevated among non-Hispanic Black AYAs., Conclusions: Results of this study suggest that noncancer mortality after AYA cancer is highest among survivors who are non-Hispanic Black or live in the South or in rural counties., Impact: Our analyses highlight disparities among AYAs with cancer and identify subgroups that may be targeted for increased medical surveillance or behavioral interventions., (©2019 American Association for Cancer Research.)

Background: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability., Methods: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling., Results: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%)., Conclusions: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education., (© 2019 American Cancer Society.)

Background: Telomeres are vital for genomic integrity and telomere length has been linked to many adverse health outcomes. Some hazardous air pollutants, or air toxics, increase oxidative stress and inflammation, two possible determinants of shortened telomere length. No studies have examined air toxic-telomere length associations in a non-occupational setting., Methods: This study included 731 Sister Study participants (enrolled 2003-2007) who were randomly selected to assess telomere length in baseline blood samples. Multiplex qPCR was used to determine telomere to single copy gene (T/S) ratios. Census tract concentration estimates of 29 air toxics from the 2005 National Air Toxics Assessment were linked to baseline residential addresses. Air toxics were classified into tertile-based categories of the exposure. Multivariable linear regression was used to estimate β coefficients and 95% confidence intervals (CI) in single pollutant models. Multipollutant groups were identified with regression trees., Results: The average T/S ratio was 1.24. Benzidine (T3vsT1 β = -0.08; 95% CI: -0.14, -0.01) and 1,4-dioxane (T3vsT1 β = -0.06; 95% CI: -0.13, 0.00) in particular, as well as carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride, were associated with shorter relative telomere length. Benzidine ( p =0.02) and 1,4-dioxane ( p =0.06) demonstrated some evidence of a monotonic trend. The regression tree identified age, BMI, physical activity, ethylene oxide, acrylonitrile, ethylidene dichloride, propylene dichloride, and styrene in multipollutant groups related to telomere length., Conclusions: In this first study of air toxics and telomere length in a non-occupational setting, several air toxics, particularly 1,4-dioxane and benzidine, were associated with shorter relative telomere length., Competing Interests: Conflicts of Interest: None declared

Background: Relative to the general population, cancer patients and survivors may have an elevated risk of mortality from noncancer causes, such as cardiovascular disease and infections, but few studies have examined rates of noncancer mortality among patients diagnosed as adolescents and young adults (AYAs) (ages 15-39 years)., Methods: The Surveillance, Epidemiology, and End Results database was used to identify AYA patients who were diagnosed with a first malignant cancer between 1973 and 2015. Rates of mortality from noncancer causes among AYAs with cancer were compared with those in the general US population using standardized mortality ratios (SMRs), adjusted for age, sex, race, and calendar year., Results: Among 235,541 AYAs with cancer, a total of 12,948 deaths from noncancer causes occurred over 3.1 million total person-years of follow-up. Overall, noncancer mortality was significantly increased among AYAs with cancer relative to the general population (SMR, 1.84; 95% CI, 1.80-1.87). SMRs were particularly elevated for infectious diseases (SMR, 5.13; 95% CI, 4.95-5.32), cardiovascular disease (SMR, 1.55; 95% CI, 1.50-1.60), and renal diseases (SMR, 2.40; 95% CI, 2.12-2.71). These associations persisted for more than 20 years after cancer diagnosis. Cancer types associated with the highest SMRs for all noncancer mortality included leukemias (SMR, 5.26), Hodgkin lymphoma (SMR, 3.12), non-Hodgkin lymphoma (SMR, 6.33), central nervous system tumors (SMR, 3.38), head and neck cancers (SMR, 2.09), and cervical/uterine cancers (SMR, 2.03)., Conclusions: AYAs with cancer have an elevated burden of mortality from noncancer causes that persists many years after cancer diagnosis, highlighting the importance of comprehensive, long-term follow-up care for noncancer conditions throughout survivorship., (© 2019 American Cancer Society.)

Anti-Müllerian hormone (AMH) is required for sexual differentiation in the fetus, and in adult females AMH is produced by growing ovarian follicles. Consequently, AMH levels are correlated with ovarian reserve, declining towards menopause when the oocyte pool is exhausted. A previous genome-wide association study identified three genetic variants in and around the AMH gene that explained 25% of variation in AMH levels in adolescent males but did not identify any genetic associations reaching genome-wide significance in adolescent females. To explore the role of genetic variation in determining AMH levels in women of late reproductive age, we carried out a genome-wide meta-analysis in 3344 pre-menopausal women from five cohorts (median age 44-48 years at blood draw). A single genetic variant, rs16991615, previously associated with age at menopause, reached genome-wide significance at P = 3.48 × 10-10, with a per allele difference in age-adjusted inverse normal AMH of 0.26 standard deviations (SD) (95% confidence interval (CI) [0.18,0.34]). We investigated whether genetic determinants of female reproductive lifespan were more generally associated with pre-menopausal AMH levels. Genetically-predicted age at menarche had no robust association but genetically-predicted age at menopause was associated with lower AMH levels by 0.18 SD (95% CI [0.14,0.21]) in age-adjusted inverse normal AMH per one-year earlier age at menopause. Our findings provide genetic support for the well-established use of AMH as a marker of ovarian reserve., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50., Methods: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers., Results: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer., Conclusions: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.

In experimental and clinical studies, green or black tea consumption has been shown to reduce oxidative stress. However, these studies involved high levels of tea consumption and may not reflect patterns in the general population. Here, we examined the association between black or green tea consumption and oxidative stress in a cross-sectional study of 889 premenopausal US women aged 35-54 years. Tea consumption was measured using the Block-98 FFQ. Urinary 8-iso-PGF2α (F2-IsoP) and 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (15-F2t-IsoP-M) were used as biomarkers of oxidative stress. These compounds were measured by MS and normalised to creatinine. Linear regression was used to calculate the geometric mean differences (GMD) and 95% CI for log-transformed urinary F2-IsoP or 15-F2t-IsoP-M in relation to black or green tea consumption. We further examined whether adjusting for caffeine impacted associations between tea and oxidative stress. Geometric means of urinary F2-IsoP and 15-F2t-IsoP-M were 1·44 (95% CI 1·39, 1·49) and 0·71 (95% CI 0·69, 0·73) ng/mg creatinine, respectively. Overall, green tea consumption was not associated with urinary F2-IsoP or 15-F2t-IsoP-M. High-level black tea consumption (≥5 cups/week compared with 0) was associated with higher 15-F2t-IsoP-M concentrations (adjusted GMD=0·10, 95 % CI 0·02-0.19) but not F2-IsoP. Adjusting for caffeine nullified the association between black tea and 15-F2t-IsoP-M. Our findings do not support the hypothesis that dietary tea consumption is inversely associated with oxidative stress.

Purpose: Invasive breast cancers are thought to arise from in situ lesions, but some ductal carcinoma in situ (DCIS) are indolent with low likelihood of progressing to invasive carcinoma. Comparison of risk factor associations between DCIS and invasive disease may elucidate which factors influence early versus late stages of carcinogenesis. Therefore, we determined whether there were differences in risk factor profiles for screen-detected DCIS and invasive breast cancer among Luminal A lesions., Methods: We conducted a case-control analysis using data from the Carolina Breast Cancer Study (1993-2001). Analyses were restricted to Luminal A tumors and screen-detected tumors among mammography-eligible women, to limit confounding by mode of detection (N = 108 DCIS; N = 203 invasive). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between risk factors and lesion type., Results: In stratified analyses, we observed qualitative differences in the direction of association for ever smoking, obese BMI, high waist-to-hip-ratio (WHR), and ≥10 years of oral contraceptive use between DCIS and invasive disease. Breastfeeding was inversely associated with invasive disease and was not associated with DCIS. Interaction tests for risk factor associations between Luminal A DCIS and invasive breast cancer were not statistically significant (p>0.05)., Conclusions: Among Luminal A tumors, established breast cancer risk factors may exert stronger effects on progression of early lesions to invasive disease, with lesser effects on risk of DCIS., Competing Interests: The authors have declared that no competing interests exist.

Background: Recreational physical activity has been consistently associated with reduced breast cancer risk. Less is known about how family history of breast cancer affects the association and whether it varies by menopausal status., Methods: The Sister Study is a cohort of 50,884 women who had a sister with breast cancer but no prior breast cancer themselves at enrollment. Women reported all recreational sport/exercise activities they participated in over the past 12 months. Hours/week and MET-hours/week of physical activity were considered in association with breast cancer risk. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated with Cox regression. Extent of family history, examined as a modifier, was characterized by a Bayesian score incorporating characteristics of the family structure., Results: During follow-up (average 8.4 years), 3,023 cases were diagnosed. Higher hours/week (HR ≥7vs<1 = 0.77; 95% CI, 0.66-0.90) and MET-hours/week (HR quartile4vs1 = 0.75; 95% CI, 0.67-0.85) of physical activity were associated with reduced postmenopausal breast cancer risk. Hours/week and MET-hours/week were associated with suggestively increased premenopausal breast cancer risk (MET-hours/week HR quartile4vs1 = 1.25; 95% CI, 0.98-1.60). Associations did not vary with extent of family history. However, the increased risk in premenopausal women may be limited to those with stronger family history., Conclusions: In women with a family history of breast cancer, physical activity was associated with reduced postmenopausal, but not premenopausal, breast cancer risk and was not modified by extent of family history., Impact: This was the first study to examine the association between physical activity and breast cancer risk in a large population with a family history of breast cancer., (©2018 American Association for Cancer Research.)

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated., Objective: To characterize breast cancer risk in relation to recent childbirth., Design: Pooled analysis of individual-level data from 15 prospective cohort studies., Setting: The international Premenopausal Breast Cancer Collaborative Group., Participants: Women younger than 55 years., Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression., Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns., Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited., Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women., Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research.

Background: The dominant invasive breast cancer histologic subtype, ductal carcinoma, shows intrinsic subtype diversity. However, lobular breast cancers are predominantly Luminal A. Both histologic subtypes show distinct relationships with patient and tumor characteristics, but it is unclear if these associations remain after accounting for intrinsic subtype., Methods: Generalized linear models were used to estimate relative frequency differences (RFDs) and 95% confidence intervals (95% CIs) for the associations between age, race, tumor characteristics, immunohistochemistry (IHC) and RNA-based intrinsic subtype, TP53 status, and histologic subtype in the Carolina Breast Cancer Study (CBCS, n = 3,182) and The Cancer Genome Atlas (TCGA, n = 808)., Results: Relative to ductal tumors, lobular tumors were significantly more likely to be Luminal A [CBCS RNA RFD: 44.9%, 95% CI (39.6, 50.1); TCGA: RFD: 50.5%, 95% CI (43.9, 57.1)], were less frequent among young (≤ 50 years) and black women, were larger in size, low grade, less frequently had TP53 pathway defects, and were diagnosed at later stages. These associations persisted among Luminal A tumors (n = 242)., Conclusions: While histology is strongly associated with molecular characteristics, histologic associations with age, race, size, grade, and stage persisted after restricting to Luminal A subtype. Histology may continue to be clinically relevant among Luminal A breast cancers.

Background: Cardiovascular disease (CVD) risk is an important health concern among survivors of breast cancer. However, few studies to date have examined whether trajectories of CVD risk and major risk factors are worse among women with a breast cancer diagnosis compared with those without., Methods: Changes in weight, body mass index, waist circumference, systolic blood pressure, and 10-year CVD risk were compared between women with (813 women) and without (1049 women) an incident breast cancer diagnosis while they were enrolled in the National Institute of Environmental Health Sciences Sister Study cohort. Blood pressure and adiposity measures were collected by trained examiners at an enrollment visit (≥1 year before breast cancer diagnosis) and a second home visit 4 to 11 years later (≥1 year after breast cancer diagnosis). The non-laboratory-based Framingham risk score, a measure of 10-year general CVD risk, was calculated at both the enrollment and second visits. All analyses were stratified by menopausal status at the time of enrollment., Results: Women who were premenopausal at the time of enrollment experienced moderate increases in weight, waist circumference, systolic blood pressure, and CVD risk over the study period. Those who were postmenopausal at the time of enrollment demonstrated little change in weight, but were found to have increases in waist circumference, systolic blood pressure, and CVD risk. In both groups, changes over time did not differ significantly according to breast cancer status. Neither chemotherapy nor endocrine therapy were found to be associated with greater increases in CVD risk or risk factors., Conclusions: In the current study cohort, changes over time in CVD risk, adiposity measures, and blood pressure were similar between women who developed an incident breast cancer and those who did not., (© 2018 American Cancer Society.)

Objective: To study the associations between dietary factors and circulating antimüllerian hormone (AMH) concentrations among late premenopausal women., Design: AMH concentrations were measured in serum samples collected at enrollment from 296 women (aged 35-45 years) in the Sister Study cohort. Usual dietary intakes in the past 12 months were assessed using a validated food frequency questionnaire. Dietary exposures of interest included macronutrients, dietary fat subtypes, fiber, and glycemic index. Multivariable linear regression was used to evaluate associations between dietary variables and serum AMH concentrations. We also used nutrient density models to examine isocaloric replacement of macronutrients., Setting: Not applicable., Patients: Women aged 35-45 years., Interventions: Not applicable., Main Outcome Measures: Serum AMH concentrations in nanograms per milliliter (ng/mL)., Results: AMH concentrations were positively associated with percentage of energy from carbohydrates (β per 5% calories = 0.141 [95% CI 0.023, 0.259]; P trend = .019), and inversely associated with percentage of energy from fat (β per 5% calories = -0.152 [95% CI -0.299, -0.004]; P trend = .044). In analyses of dietary fat subtypes, AMH decreased with increasing monounsaturated fatty acids (P trend = .082) and polyunsaturated fatty acids (P trend = .043), particularly ω-6 fatty acids (P trend = .044), whereas no strong trend was observed for saturated fatty acids. Protein and alcohol intake were not strongly associated with AMH., Conclusions: Our cross-sectional analyses in a sample of late premenopausal women suggest that dietary fat intake may be inversely associated with circulating AMH concentrations. Further research in prospective studies is warranted to evaluate dietary factors as potential modifiers of ovarian reserve., (Copyright © 2018 American Society for Reproductive Medicine. All rights reserved.)

Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation., Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics., Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017., Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years., Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer., Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall., Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

Objective: Previous studies have suggested that suicide rates are elevated among cancer patients relative to the general population. In this analysis, we comprehensively evaluated characteristics associated with higher suicide rates among patients with cancers of the digestive system., Methods: Using the United States Surveillance, Epidemiology, and End Results database, we identified all patients diagnosed with digestive system cancers during 2000 to 2014. Patients were classified as having died of suicide if their cause of death in Surveillance, Epidemiology, and End Results was listed as "suicide and self-inflicted injury." Suicide rates were compared to age-, sex-, and race-adjusted rates in the general population., Results: A total of 881 suicides were identified among 856 293 patients diagnosed with digestive system cancers. The suicide rate in this population was 32.8 per 100 000 person-years and was nearly twice that in the general population (standardized mortality ratio [SMR] = 1.91; 95% CI, 1.79-2.04). Suicide rates were significantly elevated for all cancer sites but were highest for esophageal (SMR = 5.03), pancreatic (SMR = 5.28), stomach (SMR = 2.84), and liver (SMR = 2.14) cancers. Standardized mortality ratios for suicide were highest within the first 5 years of diagnosis and increased with age at diagnosis for all sites except colon and stomach., Conclusions: Patients with cancers of the digestive system have a higher incidence of suicide than the general population. Suicide rates among esophageal and pancreatic cancer patients are more than 5 times general population rates. The involvement of psychiatrists and other mental health professionals may be a critical component of cancer care for these high-risk patient subgroups., (© 2018 John Wiley & Sons, Ltd.)

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications., (© 2018 Wiley Periodicals, Inc.)

Purpose: Annually, > 45,000 US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics., Methods: We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15-39 during 2000-2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression., Results: Among 17,564 AYA cancer survivors, 1989 had ≥ 1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007-2012, compared to 9.4% during 2000-2005 (HR = 1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006., Conclusions: Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15 years., Implications for Cancer Survivors: Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis.

Background: Many studies have examined long-term outcomes after childhood cancer, but few address outcomes for adolescent and young adult (AYA; those aged 15-39 years) cancer survivors. Conditional survival reflects changing mortality risk with time since cancer diagnosis and is a useful measure for planning long-term follow-up care., Methods: Using the Surveillance, Epidemiology, and End Results registry 9 database, the authors identified a cohort of AYA patients diagnosed with a first malignant cancer between 1973 and 2009 and followed through 2014. They estimated 5-year relative survival at the time of diagnosis and at each additional year survived up to 25 years after diagnosis, conditional on the individual being alive at the beginning of that year., Results: A total of 205,954 AYA patients with cancer were identified. Thyroid cancer, melanoma, testicular cancer, breast cancer, lymphoma, leukemia, and central nervous system (CNS) tumors comprised 67% of all cancers. For all cancers combined, 5-year relative survival was 84.5% (95% confidence interval, 84.3%-84.7%) at 1 year after diagnosis and 94.0% (95% CI, 93.9%-94.2%) at 5 years. The relative survival first exceeded 95%, reflecting minimal excess mortality compared with the general population, at 7 years. Patients with thyroid cancer, testicular cancer, melanoma, and breast cancer reached a relative survival of >95% at the time of diagnosis and at 1, 3, and 18 years after diagnosis, respectively. Estimates for those with Hodgkin lymphoma and leukemia were >95% at 6 and 13 years, respectively, but declined to <95% at 20 years. AYA individuals with CNS tumors did not reach 95% by 25 years after diagnosis., Conclusions: For AYA survivors of breast cancer, CNS tumors, and hematologic malignancies, long-term excess mortality should be considered when planning follow-up care. Cancer 2018;124:3037-43. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Purpose: Cancer survivors are at increased risk for the early development of age-related chronic medical conditions compared with peers without a history of cancer; however, little is known regarding the burden of these conditions among survivors of adolescent and young adult (AYA) cancers. In response, we sought to determine the prevalence of specific comorbidities and frailty among AYAs (15-39 years old at diagnosis) enrolled in a cancer survivorship cohort., Methods: Using a cross-sectional survey of a tertiary medical center-based cancer survivorship cohort, we determined the prevalence of specific comorbidities and frailty using the survey-based FRAIL assessment. In separate models adjusting for age, we estimated prevalence ratios (PRs) for the associations between patient characteristics and (1) any comorbidity and (2) frailty or prefrailty using log-binomial models., Results: We identified 271 AYA cancer survivors, most of whom were 30-39 years old at survey (57%). A majority of survivors (n = 163, 60%) reported having at least one comorbidity with the most common being depression (28%), anxiety (27%), asthma (17%), high cholesterol (15%), and hypertension (15%). Of the 184 AYA survivors at least 1 year from cancer diagnosis, 19 (10%) were classified as frail and 39 (21%) as prefrail. Survivors who were smokers (PR 2.0, 95% confidence interval [CI]: 1.16-3.56); obese (PR 1.7, 95% CI: 1.10-2.55); uninsured (PR 2.7, 95% CI: 1.63-4.59); or who reported comorbid depression or anxiety (PR 2.4, 95% CI: 1.51-3.67) were more likely to be frail or prefrail., Conclusions: The prevalence of frailty and comorbidities is high among AYA cancer survivors suggestive of accelerated aging.

A strong positive association has been observed between circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (p trend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (p interaction  = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: OR Q4-Q1  = 1.96, 95% CI = 1.46-2.64, p trend <0.0001; ER+/PR-: OR Q4-Q1  = 0.82, 95% CI = 0.40-1.68, p trend  = 0.51; ER-/PR+: OR Q4-Q1  = 3.23, 95% CI = 0.48-21.9, p trend  = 0.26; ER-/PR-: OR Q4-Q1  = 1.15, 95% CI = 0.63-2.09, p trend  = 0.60. The association was observed for both pre- (OR Q4-Q1 = 1.35, 95% CI = 1.05-1.73) and post-menopausal (OR Q4-Q1  = 1.61, 95% CI = 1.03-2.53) breast cancer (p interaction  = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH., (© 2018 UICC.)

Reproductive outcomes are an important survivorship concern for women diagnosed with cancer as adolescents and young adults (AYAs). We examined the incidence of live birth and the prevalence of adverse birth outcomes according to tumor and treatment characteristics among AYAs with breast cancer. Women diagnosed with breast cancer at ages 15-39 during 2000-2013 were identified using the North Carolina Central Cancer Registry (n = 4,978). Cancer registry records were linked to state birth certificate files from 2000 to 2014 to identify births to women with and without a breast cancer history. The breast cancer cohort was followed until live birth, death, age 46, or December 31, 2014, whichever occurred first. For each birth to breast cancer survivors (n = 338), we sampled 20 births to women without a recorded cancer diagnosis, with frequency matching on maternal age and year of delivery. The cumulative incidence of live births after breast cancer was 8% at 10 years. Births were less common among women treated with chemotherapy. Overall, the prevalence of preterm birth, low birth weight, small-for-gestational age (SGA) and Cesarean delivery did not differ substantially between births to women with and without breast cancer. However, births to women with ER-negative disease were more likely to be preterm (PR = 1.84; 95% CI: 1.11-3.06). In this population-based study, <10% of AYA breast cancer survivors had a live birth within 10 years of their diagnosis. The increase in risk of preterm delivery among ER-negative survivors in our cohort warrants further investigation in larger studies., (© 2017 UICC.)

Objective: To describe the patterns of prescription drug use among child and adolescent survivors of cancer in the early post-therapy period compared with matched peers without a cancer history., Study Design: Using the MarketScan commercial insurance claims database, we performed a retrospective cohort study identifying survivors of pediatric (0-21 years of age at diagnosis) leukemia, lymphoma, central nervous system, bone, or gonadal cancers who completed therapy from 2000 to 2011 and remained insured for 3 years post-therapy. Prescription fills during the first 3 years post-therapy were examined, categorized by drug class, and compared with age-, sex-, and region-matched individuals without cancer., Results: We identified 1414 survivors and 14 007 comparators. Compared with those without cancer, survivors had 1.5-4.5 times greater risk for filling opioids. Survivors of leukemia, lymphoma, central nervous system, and bone cancers had 2-5 times the risk for antidepressant and 3-7 times the risk for anxiolytic use. Survivors of leukemia, lymphoma, and bone tumors had 3-13 times the risk for angiotensin-converting enzyme inhibitors by the third year post-therapy., Conclusion: Compared with peers without cancer, survivors of childhood cancer have greater rates of prescription use across many drug classes, suggesting greater medical morbidity. Survivors were more likely to use opioid, psychoactive, hormone, and cardiovascular medications. All general pediatricians and subspecialists should be aware of potentially emerging morbidities during the early post-therapy period to guide risk-based surveillance and survivorship care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer., Objective: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003-2009)., Methods: Non-Hispanic black (4,452) and white women (n=42,453) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence., Results: A total of 2,326 women developed breast cancer during follow-up (average follow-up=5.4y). Among black women, none of the latent class hazard ratios was elevated, but there were <100 cases in any category, limiting power. Among white women, those classified as "moderate" and "frequent" users of beauty products had increased risk of breast cancer relative to "infrequent" users [HR=1.13 (95% CI: 1.00, 1.27) and HR=1.15 (95% CI: 1.02, 1.30), respectively]. Frequent users of skincare products also had increased risk of breast cancer relative to infrequent users [HR=1.13 (95% CI: 1.00, 1.29)]. None of the hair product classes was associated with increased breast cancer risk. The associations with beauty and skin products were stronger in postmenopausal women than in premenopausal women, but not significantly so., Conclusions: This work generates novel hypotheses about personal care product use and breast cancer risk. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated. https://doi.org/10.1289/EHP1480.

Oxidative stress is one hypothesized mechanism linking anthropometric, behavioral, and medical risk factors with cardiovascular disease (CVD). We evaluated cross-sectional associations between CVD risk factors and biomarkers of oxidative stress, and investigated these biomarkers as predictors of incident diabetes and hypertension among premenopausal women. F 2 -isoprostane (F 2 -IsoP) and metabolite (15-F 2t -IsoP-M), reliable biomarkers of oxidative stress, were measured in urine samples collected at enrollment from 897 premenopausal women (ages 35-54) enrolled in the Sister Study cohort without a CVD history. Blood pressure, waist circumference, and body mass index (BMI) were measured at enrollment by trained study personnel. Diabetes and cigarette smoking were self-reported via enrollment questionnaires. Over a maximum follow-up of 11.5 years, participants self-reported incident diabetes and hypertension diagnoses on mailed questionnaires. In cross-sectional analyses, both F 2 -IsoP and 15-F 2t -IsoP-M were positively associated with BMI, waist circumference, diastolic blood pressure, and current smoking. F 2 -IsoP was elevated among those with diabetes, and 15-F 2t -IsoP-M increased with higher systolic blood pressure. Prospective analyses suggested an increased hypertension risk among those with elevated 15-F 2t -IsoP-M (highest vs. lowest quartile: hazard ratio=2.34; 95% CI: 1.20-4.56). Our results suggest that urinary F 2 -IsoP and 15-F 2t -IsoP-M are positively associated with adiposity measures, blood pressure, and cigarette smoking. Further investigation is warranted to evaluate 15-F 2t -IsoP-M as a predictor of hypertension., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: A cancer diagnosis in adolescence and young adulthood (AYA, ages 15-39) may affect future pregnancy outcomes. Previous studies have reported an increased risk of preterm delivery (< 37 weeks of gestation) after maternal cancer treatment. In this analysis, we evaluated whether non-cancer characteristics modify the association between an AYA cancer history and preterm birth., Methods: North Carolina Central Cancer Registry records (2000-2013) were linked to state birth certificate files (2000-2014) to identify births to AYA cancer survivors (n = 1,980). A comparison cohort of births to women without a cancer diagnosis was selected from birth certificate files (n = 11,860). Log-binomial regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. Effect modification by early prenatal care (1st trimester; yes/no), race/ethnicity (white/black/other), previous live births (0/1+), maternal age (< 25/25-29/30-34/35+), smoking during pregnancy (any/none), and education (high school or less/some college/Bachelor's degree or higher) was evaluated using likelihood ratio tests (LRT)., Results: Overall, preterm births were more common among AYA survivors than the comparison group (RR = 1.24, CI 1.07-1.43). The association was stronger among those who did not receive early prenatal care (RR = 1.73, CI 1.26-2.37) than among those who did (RR = 1.15, CI 0.98-1.35; LRT p = 0.03). Maternal age < 25 was also associated with a greater increase in preterm birth (< 25: RR = 1.80, CI 1.27-2.54; LRT p = 0.07). Associations did not vary strongly by other factors evaluated., Conclusions: An AYA cancer diagnosis may be associated with an increased risk of preterm birth, particularly among women who are younger and receive late or no prenatal care.

Background: Diets with a high glycemic index (GI) and glycemic load (GL) have been hypothesized to increase oxidative stress, but the limited human studies are inconsistent., Objective: The aim of this cross-sectional study was to investigate associations between dietary GI, GL, and carbohydrate intake and oxidative stress, as measured by F2-isoprostanes (F2-IsoPs)., Methods: Concentrations of F2-IsoP and its metabolite (15-F2t-IsoP-M) were measured in urine samples collected at enrollment from 866 premenopausal women (aged 35-54 y) participating in the Sister Study. Total carbohydrate intake and dietary GI and GL were assessed using a validated food frequency questionnaire. Urinary F2-IsoP and 15-F2t-IsoP-M concentrations were compared across quintiles of carbohydrate intake, GI, and GL using multivariable linear regression models., Results: Urinary F2-IsoP concentrations were positively associated with dietary GI (P-trend = 0.023), and both F2-IsoP and 15-F2t-IsoP-M concentrations were positively associated with GL (F2-IsoP: P-trend < 0.001; 15-F2t-IsoP-M: P-trend < 0.001) and total carbohydrate intake (F2-IsoP: P-trend = 0.012; 15-F2t-IsoP-M: P-trend < 0.001). Stratified analyses suggested that a positive association between GI and urinary 15-F2t-IsoP-M concentrations was present among women with a body mass index [BMI (in kg/m2)] ≥30.0, but not among those with a BMI of <25.0 or 25.0-29.9 (P-interaction = 0.01)., Conclusions: Our cross-sectional analyses in a sample of premenopausal women support hypothesized relations between high dietary GI and GL and oxidative stress, as assessed by urinary F2-IsoP and 15-F2t-IsoP-M concentrations. Given potential associations between oxidative stress and the development of cardiovascular disease and type 2 diabetes, our findings may have important implications for reducing chronic disease risk., (Copyright © 2017 American Society for Nutrition. All rights reserved.)

Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype., Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+)., Results: In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype., Conclusions: Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.

Background: African American (AA) women have higher incidence of aggressive, young-onset (<40 years) breast cancers. Young- and older-onset disease may have distinct tumor biologies and etiologies; however, studies investigating age differences among AA women have been rare and generally underpowered. Methods: We examined tumor characteristics and breast cancer risk factors associated with premenopausal young (<40) vs. older (≥40) AA women's breast cancer in the African American Breast Cancer Epidemiology and Risk Consortium (2,008 cases and 5,144 controls). Unconditional logistic regression models assessed heterogeneity of tumor biology and risk factor associations by age, overall, and by estrogen receptor status. Results: Premenopausal AA women <40 years had higher frequency of poorer-prognosis tumor characteristics compared with older women, including negative estrogen and progesterone receptor status, triple-negative subtype, higher grade, higher stage, and larger tumors. Adiposity (i.e., waist-to-hip ratio) and family history of breast cancer were more strongly associated with young-onset disease [case-control OR = 1.46, 95% confidence interval (CI) = 1.04-2.05; OR = 3.10, 95% CI = 2.08-4.63, respectively] compared with older-onset disease (OR = 1.11, 95% CI = 0.91-1.35; OR = 1.57, 95% CI = 1.26-1.94). Breastfeeding showed a slight inverse risk association among young women (OR = 0.70, 95% CI = 0.43-1.16). Oral contraceptive use was associated with increased risk regardless of age. Considering various cutoff points for young age (<40, <45, <50), age-related heterogeneity was greatest when <40 was used. Conclusions: Among premenopausal AA women, diagnosis before age 40 is associated with more aggressive breast tumor biology and some etiologic differences. Impact: Modifiable risk factors including breastfeeding, adiposity, and oral contraceptive use may be important targets for mitigating harms of young-onset breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1722-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Treatment with radioactive iodine (RAI) for differentiated thyroid cancer has been associated with alterations in gonadal function in women, including changes in menstrual function and an earlier age at menopause. Our objective was to evaluate associations between RAI and postdiagnosis live birth rates among thyroid cancer survivors diagnosed at ages 15-39 years. We identified women diagnosed with differentiated thyroid cancer between January 2000 and December 2013 in the North Carolina Central Cancer Registry (CCR). CCR records were linked to state birth certificate files to identify livebirths to thyroid cancer survivors through December 2014. Person-years of follow-up were accrued from 6 months after diagnosis to first birth, 46th birthday, death, or December 31, 2014, whichever came first. Cox proportional hazards regression was used to estimate hazards ratios (HR) and 95% confidence intervals (CI) for first livebirth. Among 2,360 women with a differentiated thyroid cancer diagnosis, 53% received RAI. The cumulative incidence of birth at the end of follow-up (maximum 14.5 years) was 30.0 and 29.3% among those who were and were not treated with RAI, respectively. Overall, first birth rates did not significantly differ between groups (HR = 1.00; 95% CI: 0.82, 1.23). In our observational cohort, treatment with RAI was not associated with a reduced birth rate. Our findings add to the evidence available for counseling thyroid cancer patients with concerns about future fertility., (© 2017 UICC.)

Increasing numbers of women in the US are getting too little sleep. Inadequate sleep has been associated with impaired metabolic function and endocrine disruption. Sister Study cohort participants (n = 50,884), completed baseline and follow-up questionnaires on sleep patterns. Incident breast cancers estrogen receptor (ER) status of the tumor were ascertained from questionnaires and medical records. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses of sleep characteristics reported at the first follow-up interview included only participants who were breast cancer-free at time of follow-up interview. Over ∼7 years of follow-up, 2,736 breast cancer cases (invasive and ductal carcinoma in situ) were diagnosed. There was little evidence that usual sleep duration or other sleep characteristics were associated with breast cancer. However, relative to those with no difficulty sleeping, women who reported having difficulty sleeping ≥ 4 nights a week were at an increased risk of overall (HR = 1.32, 95% CI: 1.09-1.61) and postmenopausal breast cancer (HR = 1.51, 95% CI 1.24-1.85). Risk of ER+ invasive cancer was elevated for women who reported having a light or television on in the room while sleeping (HR = 1.20, 95% CI: 0.97-1.47) or who typically got less sleep than they needed to feel their best (HR = 1.21, 95% CI: 0.98-1.50). In our study, most sleep characteristics, including sleep duration, were not associated with an increased risk although higher risk was observed for some markers of inadequate or poor quality sleep., (©Published 2017. This article is a US Government work and, as such, is in the public domain of the United States of America.)

Purpose: National guidelines encourage counseling high-risk women about pharmacologic breast cancer risk reduction. We evaluated the use of integrated health care data to identify and characterize breast cancer chemoprevention use. Chemoprevention included US Food and Drug Administration-approved use of tamoxifen and raloxifene and off-label use of aromatase inhibitors (AIs)., Patients and Methods: Using electronic medical and pharmacy records (EMRs) in the Kaiser Permanente Northern California health care system, we sampled cancer-free women age 35 to 69 years who used tamoxifen, raloxifene, exemestane, anastrozole, or letrozole from 2005 to 2013. Risk-benefit profiles were calculated for tamoxifen and raloxifene using published indices. The proportion of days covered was calculated from pharmacy records to assess adherence., Results: Among 90 chemoprevention users (confirmed with EMR review from a sample of 371 women), 74% used tamoxifen, 11% used raloxifene, and 13% used an AI. For tamoxifen and raloxifene users, the risk-benefit index indicated 23% of women had insufficient evidence that benefits would outweigh risks. For all agents, adherence decreased from an average proportion of days covered of 75% at 1 year to 67% at 5 years. Automated EMR searches identified breast cancer chemoprevention users with 60% positive predictive value overall and 75% for tamoxifen after post hoc modifications., Conclusion: Our study contributes to an emerging picture of breast cancer chemoprevention use in real-world settings, where evidence of net benefit is not uniform and nonadherence is common. Among breast cancer chemoprevention agents, our automated selection best performed for tamoxifen use. We also identified off-label use of AIs for chemoprevention, suggesting that expansion of risk-benefit indices to include AIs is warranted.

Background: Women may have incomplete understanding of a breast cancer diagnosis, leading to inaccurate reporting in epidemiological studies. However, it is not feasible to obtain consent for medical records from all women participating in a study. Therefore, it is important to determine how well self-reported breast cancer characteristics correspond with what is found in medical records, but few studies have evaluated agreement of self-reported breast cancer characteristics with abstracted medical records., Methods: We calculated the positive predictive value (PPV) of self-reports compared to medical records and explored whether participant characteristics may have influenced reporting accuracy. We analyzed data from 2518 reported breast cancer cases from the Sister Study, a large nationwide cohort of women with a family history of breast cancer., Results: Medical records or pathology reports were obtained for 2066 of 2518 (82%) women who reported incident breast cancer. Breast cancer was confirmed for over 99% (n = 2054) of women with medical records. Confirmation rates were high for invasive, ductal, hormone receptor positive, and HER2 negative breast cancers, with little variation by race/ethnicity or age. Self-reported in situ breast cancer had a lower PPV (64.2%), with medical records showing invasive breast cancer instead, especially for older and Hispanic women. Hormone receptor (ER and PR) negative and HER2 positive self-reports had lower PPVs (83.0%, 71.6%, and 66.1% respectively). Hispanic women and women ages 65 or older at diagnosis were less able to accurately report breast cancer stage, excluding stage I., Conclusions: Accuracy of reporting overall breast cancer and common subtypes is high. Despite having a family history of breast cancer and voluntarily enrolling in a study evaluating breast cancer risk factors, participants may have greater difficulty distinguishing between in situ and invasive breast cancer and may less accurately report other less common subtypes. Discrepancies may reflect women's poor understanding of information conveyed by health care providers or lack of consistent terminology used to describe subtypes.

It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N=47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks.

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause., Methods: We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression., Results: After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (≥2.94 ng/mgCr) to <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m (OR: 0.98, CI: 0.39, 2.5, 138 cases)., Conclusions: Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk.

Importance: Cancer diagnosis and treatment may adversely affect reproductive outcomes among female cancer survivors., Objective: To compare the birth outcomes of adolescent and young adult cancer survivors (AYA [diagnosed at ages 15-39 years]) with those of women without a cancer diagnosis., Design, Setting, and Participants: The North Carolina Central Cancer Registry (CCR) was used to identify female AYA cancer survivors diagnosed from January 2000 to December 2013; CCR records were linked to statewide birth certificate files from January 2000 to December 2014 to identify postdiagnosis live births to AYA survivors (n = 2598). A comparison cohort of births to women without a recorded cancer diagnosis was randomly selected from birth certificate files (n = 12 990) with frequency matching on maternal age and year of delivery., Main Outcomes and Measures: Prevalence of preterm birth, low birth weight, small-for-gestational-age births, cesarean delivery, and low Apgar score., Results: Overall, 2598 births to AYA cancer survivors (mean [SD] maternal age, 31 [5] years) were included. Births to AYA cancer survivors had a significantly increased prevalence of preterm birth (prevalence ratio [PR], 1.52; 95% CI, 1.34-1.71), low birth weight (PR, 1.59; 95% CI, 1.38-1.83), and cesarean delivery (PR, 1.08; 95% CI, 1.01-1.14) relative to the comparison cohort of 1299. The higher prevalence of these outcomes was most concentrated among births to women diagnosed during pregnancy. Other factors associated with preterm birth and low birth weight included treatment with chemotherapy and a diagnosis of breast cancer, non-Hodgkin lymphoma, or gynecologic cancers. The prevalence of small-for-gestational-age births and low Apgar score (<7) did not differ significantly between groups., Conclusions and Relevance: Live births to AYA cancer survivors may have an increased risk of preterm birth and low birth weight, suggesting that additional surveillance of pregnancies in this population is warranted. Our findings may inform the reproductive counseling of female AYA cancer survivors.

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

Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (≥88 cm); elevated blood pressure (≥130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol-lowering medication use. During follow-up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m 2 with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m 2 and ≥1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR = 1.26, 95% CI: 1.01-1.56), as did women with a BMI ≥25 kg/m 2 and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR = 1.24, 95% CI: 0.99-1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ≥88 cm, waist circumference ≥80 cm, and waist-hip ratio ≥0.85 of 1.58, 95% CI: 1.02-2.46; 1.38, 95% CI: 1.09-1.75; and 1.38, 95% CI: 1.02-1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR = 0.71, 95% CI: 0.52-0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI., (© 2017 UICC.)

Background: Contralateral prophylactic mastectomy (CPM) rates have been increasing in the US, and although high levels of satisfaction with CPM have been reported, few studies have evaluated the long-term effects on body image, comparing CPM with breast-conserving surgery (BCS) and unilateral mastectomy (UM)., Methods: We analyzed responses from a survey of women with both a personal and family history of breast cancer who were enrolled in the Sister Study (n = 1176). Among women who underwent mastectomy, we examined satisfaction with the mastectomy decision, as well as variation in the use of reconstruction and experience of complications. Five survey items, evaluated individually and as a summed total score, were used to compare body image across surgery types (BCS, UM without reconstruction, CPM without reconstruction, UM with reconstruction, and CPM with reconstruction)., Results: Participants were, on average, 3.6 years post-diagnosis at the time of survey (standard deviation 1.7). The majority of women (97% of CPM, 89% of UM) were satisfied with their mastectomy decision. Reconstruction was more common after CPM than after UM (70 vs. 47%), as were complications (28 vs. 19%). Body image scores were significantly worse among women who underwent CPM than among women who underwent BCS, with the lowest scores among women who underwent CPM without reconstruction., Conclusions: In our sample, most women were highly satisfied with their mastectomy decision, including those who elected to undergo CPM. However, body image was lower among those who underwent CPM than among those who underwent BCS. Our findings may inform decisions among women considering various courses of surgical treatment.

Expanding research capacity of large research networks within health care delivery systems requires strategically training both embedded and external investigators in necessary skills for this purpose. Researchers new to these settings frequently lack the skills and specialized knowledge conducive to multi-site and multi-disciplinary research set in delivery systems. This report describes the goals and components of the Cancer Research Network (CRN) Scholars Program, a 26-month training program developed to increase the capacity for cancer research conducted within the network's participating sites, its progression from training embedded investigators to a mix of internal and external investigators, and the content evolution of the training program. The CRN Scholars program was launched in 2007 to assist junior investigators from member sites develop independent and sustainable research programs within the CRN. Resulting from CRN's increased emphasis on promoting external collaborations, the 2013 Scholars program began recruiting junior investigators from external institutions committed to conducting delivery system science. Based on involvement of this broader population and feedback from prior Scholar cohorts, the program has honed its focus on specific opportunities and issues encountered in conducting cancer research within health care delivery systems. Efficiency and effectiveness of working within networks is accelerated by strategic and mentored navigation of these networks. Investing in training programs specific to these settings provides the opportunity to improve multi-disciplinary and multi-institutional collaboration, particularly for early-stage investigators. Aspects of the CRN Scholars Program may help inform others considering developing similar programs to expand delivery system research or within large, multi-disciplinary research networks.

Objective: The aim of this study was to identify demographic and treatment-related factors associated with health-promoting behavior changes after a breast cancer diagnosis. Changes in health behaviors were also evaluated according to weight, exercise, diet and alcohol consumption patterns before breast cancer diagnosis., Materials and Methods: We examined self-reported behavior changes among 1415 women diagnosed with breast cancer in the NIEHS Sister Study cohort. Women reported changes in exercising, eating healthy foods, maintaining a healthy body weight, drinking alcohol, smoking, getting enough sleep, spending time with family and friends, and participating in breast cancer awareness events., Results: On average, women were 3.7 years from their breast cancer diagnosis. Overall, 20-36% reported positive changes in exercise, eating healthy foods, maintaining a healthy weight, or alcohol consumption. However, 17% exercised less. With each 5-year increase in diagnosis age, women were 11-16% less likely to report positive change in each of these behaviors (OR = 0.84-0.89; p < 0.05), except alcohol consumption (OR = 0.97; CI: 0.81, 1.17). Women who underwent chemotherapy were more likely to report eating more healthy foods (OR = 1.47; 95% CI 1.16-1.86), drinking less alcohol (OR = 2.01; 95% CI: 1.01, 4.06), and sleeping enough (OR = 1.41; 95% CI: 1.04, 1.91). The majority of women (50-84%) reported no change in exercise, eating healthy foods, efforts to maintain a healthy weight, alcohol consumption, sleep patterns, or time spent with family or friends., Conclusions: Many women reported no change in cancer survivorship guideline-supported behaviors after diagnosis. Positive changes were more common among younger women or those who underwent chemotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Though randomized clinical trials have demonstrated a reduction in second breast events with endocrine therapy among women with ductal carcinoma in situ (DCIS), use of these therapies remains highly variable. The purpose of this study was to evaluate patient and treatment-related factors associated with endocrine therapy initiation and medical oncology specialty utilization after DCIS., Materials and Methods: We identified women with a DCIS diagnosis during 2006-2010 in the North Carolina Central Cancer Registry with linked public and private insurance claims in the University of North Carolina Integrated Cancer Information Surveillance System data resource. Multivariable generalized linear regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for endocrine therapy initiation in the year following DCIS diagnosis., Results: Among 2,090 women with a DCIS diagnosis, 37% initiated endocrine therapy. Initiation was less common among women aged 75+ at diagnosis (RR = 0.79; 95% CI: 0.64-0.97 vs. age 45-54) and women treated with breast-conserving surgery (BCS) who did not receive radiation (RR = 0.63; 95% CI: 0.50-0.78 vs. BCS plus radiation). Consultation with a medical oncologist was strongly associated with endocrine therapy initiation (RR = 1.40; 95% CI: 1.23-1.61). Women who saw a medical oncologist more often had private insurance, higher census tract-level income, hormone receptor positive disease, and treatment with BCS and radiation., Conclusion: Treatment strategies for DCIS remain controversial. Our data suggest that endocrine therapy is more often used in addition to standard therapies such as BCS plus radiation, rather than as an alternative to radiation. The Oncologist 2017;22:535-541 IMPLICATIONS FOR PRACTICE: Randomized trials have demonstrated a reduction in second breast cancer events with use of endocrine therapy for ductal carcinoma in situ (DCIS). However, notable variation exists in the uptake of these therapies among DCIS patients. In this study, factors associated with endocrine therapy initiation in the year following a DCIS diagnosis included consultation with a medical oncologist and treatment with breast-conserving surgery with radiation. Our findings help to explain the wide variation in endocrine therapy initiation and suggest the need for clear guidelines in the treatment of DCIS., (© AlphaMed Press 2017.)

Background: Black-white disparities in breast cancer incidence rates and birth outcomes raise concerns about potential disparities in the reproductive health of premenopausal breast cancer survivors. We examined the prevalence of preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) by breast cancer history and effect modification by race., Methods: We analyzed linked North Carolina birth records and Central Cancer Registry files from 1990 to 2009 (n = 2,325,229). We used multivariable negative log-binomial regression to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between breast cancer history and PTB, LBW, and SGA., Results: Of 1,912,269 eligible births, 512 births were to mothers with a previous breast cancer diagnosis history. Average age at breast cancer diagnosis was 31.8 years (SD = 4.7). Mean time from diagnosis to delivery was 3.3 years (SD = 2.8). After multivariable adjustment, the PR was 1.67 (95% CI, 1.42-1.97) for PTB, 1.50 (95% CI, 1.23-1.84) for LBW, and 1.30 (95% CI, 1.05-1.61) for SGA comparing women with a breast cancer history to the general population. Among black mothers, the PRs associated with breast cancer history for PTB, LBW, and SGA were 1.31 (95% CI, 1.00-1.72), 1.49 (95% CI, 1.14-1.94), and 1.44 (95% CI, 1.11-1.87), respectively. The corresponding PRs among white mothers were 2.06 (95% CI, 1.67-2.54), 1.53 (95% CI, 1.12-2.08), and 1.10 (95% CI, 0.77-1.58), respectively. The interaction between breast cancer history and race was statistically significant for associations with PTB, but not for LBW or SGA., Conclusions: In our data, women with a breast cancer history were at higher risk of delivering a PTB, LBW, or SGA infant, especially if they received chemotherapy or gave birth within 2 years of their breast cancer diagnosis date.

Background: Although treatment of ductal carcinoma in situ (DCIS) is controversial, national guidelines recommend considering endocrine therapy for women with estrogen receptor- (ER-) positive DCIS or those undergoing breast conserving surgery (BCS) without radiation. We evaluated uptake and predictors of endocrine therapy use among older women with DCIS., Methods: In the SEER-Medicare database, we identified women aged 65+ years diagnosed with DCIS during 2007-2011. We evaluated demographic, tumor, and treatment characteristics associated with endocrine therapy initiation., Results: Among 2,945 women with DCIS, 41% initiated endocrine therapy (66% tamoxifen, 34% aromatase inhibitors). Initiation was more common among women with ER-positive than ER-negative DCIS (48% versus 16%; HR = 3.75, 95% CI: 2.91-4.83); 28% of women with unknown ER status initiated endocrine therapy. Initiation was less common after BCS alone compared to BCS with radiation (32% versus 50%; HR = 0.69, 95% CI: 0.59-0.80)., Conclusions: Less than half of older women with DCIS initiate endocrine therapy to prevent second breast cancers. Our findings suggest use was more common, but not exclusive, among women with ER-positive DCIS, but not among women who underwent BCS alone. Endocrine therapy should be targeted toward patients most likely to benefit from its use.