Assessing the Health and Economic Impact of a Potential Menthol Cigarette Ban in New York City: a Modeling Study.

Menthol in cigarettes increases nicotine dependence and decreases the chances of successful smoking cessation. In New York City (NYC), nearly half of current smokers usually smoke menthol cigarettes. Female and non-Latino Black individuals were more likely to smoke menthol-flavored cigarettes compared to males and other races and ethnicities. Although the US Food and Drug Administration recently announced that it will ban menthol cigarettes, it is unclear how the policy would affect population health and health disparities in NYC. To inform potential policymaking, we used a microsimulation model of cardiovascular disease (CVD) to project the long-term health and economic impact of a potential menthol ban in NYC. Our model projected that there could be 57,232 (95% CI: 51,967-62,497) myocardial infarction (MI) cases and 52,195 (95% CI: 47,446-56,945) stroke cases per 1 million adult smokers in NYC over a 20-year period without the menthol ban policy. With the menthol ban policy, 2,862 MI cases and 1,983 stroke cases per 1 million adults could be averted over a 20-year period. The model also projected that an average of $1,836 in healthcare costs per person, or $1.62 billion among all adult smokers, could be saved over a 20-year period due to the implementation of a menthol ban policy. Results from subgroup analyses showed that women, particularly Black women, would have more reductions in adverse CVD outcomes from the potential implementation of the menthol ban policy compared to males and other racial and ethnic subgroups, which implies that the policy could reduce sex and racial and ethnic CVD disparities. Findings from our study provide policymakers with evidence to support policies that limit access to menthol cigarettes and potentially address racial and ethnic disparities in smoking-related disease burden.

Examining Trends in Beverage Sales in New York City During Comprehensive Efforts to Reduce Sugary Drink Consumption, 2010-2015.

Since 2006, New York City (NYC) has attempted to reduce sugary drink consumption through several population-based initiatives, media campaigns and policy proposals. We estimated trends in the relative market share of sugary drinks and other beverage categories in NYC, using over 5 years of weekly, point-of-sale data from a retailer sample. We used an interrupted time series approach to assess whether changes in NYC beverage purchasing patterns occurred following the announcement of a proposed portion cap rule for consumer purchases of sugary drinks. Overall, market share of sugary drinks declined in NYC between 2010 and 2015. While the proportion of beverage volume sold that was sugary drinks was stable prior to the May 2012 portion cap rule announcement, decreases of 1.25% per year were observed in the period following the announcement compared to the period before (95% confidence interval (CI) - 1.60, - 0.90). Water/seltzer market share was increasing prior to the announcement and increased by an additional 1.03% per year in the post-announcement period (95% CI 0.48, 1.57). City-led efforts to increase public awareness about sugary drink-associated health risks in NYC may have led to reductions in consumer purchases of these beverages. Though never implemented, the portion cap proposal and accompanying media coverage may have contributed to decreases in sugary drink sales.

Flavored Tobacco Sales Prohibition (2009) and Noncigarette Tobacco Products in Retail Stores (2017), New York City.

Objectives. To assess explicit- (products clearly labeled flavored) and emergent concept- (products implying flavoring but not clearly labeled) flavored tobacco product availability following New York City's flavor restriction.Methods. We examined explicit- and concept-flavored tobacco product availability, with 2017 New York City Retailer Advertising of Tobacco Survey data (n = 1557 retailers). We assessed associations between block group-level demographic characteristics and product availability by using logistic regression.Results. Most retailers sold explicit-flavored (70.9%) or concept-flavored (69.3%) products. The proportion of non-Hispanic Black neighborhood residents predicted explicit- and concept-flavored product availability, as did having a high school within a retailer's block group for concept-flavored products.Conclusions. Explicit- and concept-flavored other tobacco products persisted throughout New York City, despite 2009 legislation restricting sales.Public Health Implications. Making local sales restrictions or federal production bans inclusive of all explicit and concept flavors would reduce retailer and industry evasion opportunities and protect the health of youths and others.

Parity, breastfeeding, and breast cancer risk by hormone receptor status and molecular phenotype: results from the Nurses' Health Studies.

BACKGROUND: Epidemiologic data suggest that parity increases risk of hormone receptor-negative breast cancer and that breastfeeding attenuates this association. Prospective data, particularly on the joint effects of higher parity and breastfeeding, are limited. METHODS: We investigated parity, breastfeeding, and breast cancer risk by hormone-receptor (estrogen (ER) and progesterone receptor (PR)) and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) in the Nurses' Health Study (NHS; 1976-2012) and NHSII (1989-2013). A total of 12,452 (ER+ n = 8235; ER- n = 1978) breast cancers were diagnosed among 199,514 women. We used Cox proportional hazards models, adjusted for breast cancer risk factors, to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Parous women had lower risk of ER+ breast cancer (vs. nulliparous, HR = 0.82 [0.77-0.88]); no association was observed for ER- disease (0.98 [0.84-1.13]; Phet = 0.03). Among parous women, breastfeeding was associated with lower risk of ER- (vs. never 0.82 [0.74-0.91]), but not ER+, disease (0.99 [0.94-1.05]; Phet < 0.001). Compared to nulliparous women, higher parity was inversely associated with luminal B breast cancer regardless of breastfeeding (≥ 3 children: ever breastfed, 0.78 [0.62-0.98]; never breastfed, 0.76 [0.58-1.00]) and luminal A disease only among women who had breastfed (≥ 3 children, 0.84 [0.71-0.99]). Basal-like breast cancer risk was suggestively higher among women with higher parity who never breastfed; associations were null among those who ever breastfed. CONCLUSIONS: This study provides evidence that breastfeeding is inversely associated with hormone receptor-negative breast cancers, representing an accessible and cost-effective risk-reduction strategy for aggressive disease subtypes.

Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population.

BACKGROUND: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history. METHODS: The Women's Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutations. RESULTS: Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0-1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC (RR = 1.4, 95% CI 1.1-1.7). Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype (RR = 5.4, 95% CI 3.0-9.5), and risk remained elevated in multiple subgroups: BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen. CONCLUSIONS: Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC.

Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies.

Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow-up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2-enriched, 378 basal-like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (p(heterogeneity) = 0.65) and menopause (p(heterogeneity) = 0.05), and current HT use (p(heterogeneity) = 0.33). Increasing parity was not associated with any subtype (p(heterogeneity) = 0.76), though age at first birth was associated with luminal A tumors only (per 1-year increase HR = 1.03 95%CI (1.02-1.05), p(heterogeneity) = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal-like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49-0.87), ptrend = 0.02), p(heterogeneity) = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non-luminal subtypes (e.g. 22-year interval vs. nulliparous HR = 1.80, 95%CI (1.08-3.00) for basal-like tumors; p(heterogeneity) = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal-like tumors, representing a potential modifiable risk factor for this aggressive subtype.

Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses' health studies.

High levels of circulating carotenoids are hypothesized to reduce breast cancer risk, potentially due to their antioxidant properties. However, little is known about the relationship between carotenoid exposure earlier in life and risk. We examined associations of premenopausal plasma carotenoids and markers of oxidative stress and risk of breast cancer among 1179 case-control pairs in the Nurses' Health Study (NHS) and NHSII. Levels of α- and ß-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin were quantified by high-performance liquid chromatography. Three fluorescent oxidation products (FlOP_360, FlOP_320, FlOP_400) were measured in a subset of participants by spectrofluoroscopy. Multivariate conditional logistic regression was used to estimate odds ratios and 95 % confidence intervals for breast cancer by quartile, as well as P values for tests of linear trend. We additionally examined whether 45 single-nucleotide polymorphisms (SNPs) in five genes involved in oxidative and antioxidative processes or carotenoid availability were associated with risk. Carotenoid measures were not inversely associated with breast cancer risk. No differences by estrogen receptor status were observed, though some inverse associations were observed among women postmenopausal at diagnosis. Plasma FlOP levels were not positively associated with risk, and suggestive inverse associations with FlOP_320 and FlOP_360 were observed. Several SNPs were associated with carotenoid levels, and a small number were suggestively associated with breast cancer risk. We observed evidence of interactions between some SNPs and carotenoid levels on risk. We did not observe consistent associations between circulating levels of premenopausal carotenoids or FlOP levels and breast cancer risk.

Murine cell line model of proneural glioma for evaluation of anti-tumor therapies.

Molecular subtypes of glioblastoma (GBM) with distinct alterations have been identified. There is need for reproducible, versatile preclinical models that resemble specific GBM phenotypes to facilitate preclinical testing of novel therapies. We present a cell line-based murine proneural GBM model and characterize its response to radiation therapy. Proneural gliomas were generated by injecting PDGF-IRES-Cre retrovirus into the subcortical white matter of adult mice that harbor floxed tumor suppressors (Pten and p53) and stop-floxed reporters. Primary cell cultures were generated from the retrovirus induced tumors and maintained in vitro for multiple passages. RNA sequencing-based expression profiling of the resulting cell lines was performed. The tumorigenic potential of the cells was assessed by intracranial injection into adult naïve mice from different strains. Tumor growth was assessed by bioluminescence imaging (BLI). BLI for tumor cells and brain slices were obtained and compared to in vivo BLI. Response to whole-brain radiation was assessed in glioma-bearing animals. Intracranial injection of Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) glioma cells led to formation of GBM-like tumors with 100 % efficiency (n = 48) and tumorigenesis was retained for more than 3 generations. The cell lines specifically resembled proneural GBM based on expression profiling by RNA-Seq. Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) cell number correlated with BLI signal. Serial BLI measured tumor growth and correlated with size and location by ex vivo imaging. Moreover, BLI predicted tumor-related mortality with a 93 % risk of death within 5 days following a BLI signal between 1 × 10(8) and 5 × 10(8) photons/s cm(2). BLI signal had transient but significant response following radiotherapy, which corresponded to a modest survival benefit for radiated mice (p < 0.05). Intracranial injection of Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) cells constitutes a novel and highly reproducible model, recapitulating key features of human proneural GBM, and can be used to evaluate tumor-growth and response to therapy.

Sodium content of menu items in New York City chain restaurants following enforcement of the sodium warning icon rule, 2015-2017.

In 2016, New York City (NYC) began enforcing a sodium warning regulation at chain restaurants, requiring placement of an icon next to any menu item containing ≥2,300 mg sodium. As menu labeling may improve menu nutritional composition, we investigated whether sodium content of menu items changed following enforcement of the sodium warning icon. All menu offerings at 10 quick-service (QSR) and 3 full-service (FSR) chain restaurants were photographed in 2015 (baseline) and 2017 (follow-up) and matched to nutritional information from restaurant websites; items were categorized as being available at both baseline and follow-up, or at only one timepoint. Linear and logistic regression models, respectively, assessed changes in calculated mean sodium-per-serving per menu item and the odds of an item containing ≥2,300 mg sodium. At baseline, mean per-serving sodium content was 2,160 mg at FSR and 1,070 mg at QSR, and 40.6% of FSR items and 7.2% of QSR items contained ≥2,300 mg sodium per serving. Sodium content did not differ when comparing all items offered at follow-up to all offered at baseline (21 mg, 95% CI: -60,101), or when comparing new versus discontinued items (17 mg, 95% CI: -154, 187). At follow-up, there was no change in the overall likelihood of items requiring a warning icon (OR = 1.32, 95% CI: 0.97,1.79), or when comparing new versus discontinued items (OR = 2.08, 95% CI: 1.02,4.24) (p = 0.04, not significant following Bonferroni correction for multiple analyses). Our findings that the sodium content of menu items did not change following the sodium warning icon regulation underscore difficulties in reducing sodium levels in restaurants; however, our results may be limited by follow-up data collection occurring less than one year post-enforcement. It may take additional time and similar action from other jurisdictions for restaurants to reduce the sodium content of menu items.

Changes in consumer purchasing patterns at New York City chain restaurants following adoption of the sodium warning icon rule, 2015-2017.

In 2016, New York City (NYC) began enforcing a sodium warning regulation at chain restaurants, requiring placement of an icon next to any menu item containing ≥2,300 mg sodium. As shifts in consumer purchases are a potential outcome of menu labeling, we investigated whether high-sodium purchases from NYC chains changed following policy implementation. Using receipts for verification, consumer purchases were assessed at 2 full-service (FSR) and 2 quick-service (QSR) chain restaurants in NYC and Yonkers, NY, which did not implement sodium menu labeling, in 2015 and 2017. Primary outcomes included the proportion of respondents purchasing high-sodium item(s) (containing ≥2,300 mg sodium) and mean sodium content of purchases; changes were assessed by difference-in-difference regression models, adjusted for demographic and location co-variates. At both FSR and QSR, there was not a significant change in the proportion of NYC respondents purchasing 1 or more high-sodium items, relative to Yonkers (FSR difference-in-difference: -4.6%, p = 0.364; QSR difference-in-difference: -8.9%, p = 0.196). Among NYC FSR respondents, mean sodium content of purchases significantly declined compared to Yonkers (difference-in-difference: -524 mg, p = 0.012); no changes in mean sodium were observed among QSR participants (difference-in-difference: 258 mg, p = 0.185). Although there was a reduction in mean sodium content of purchases among NYC FSR patrons following sodium warning icon implementation, the mechanism behind the relatively larger NYC decline is unknown.

What proportion of lung cancer in never-smokers can be attributed to known risk factors?

Though tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime nonsmokers. In this article, we calculate the burden of lung cancer in never-smokers attributable to previously identified risk factors in North America, Europe and China, using population-based estimates of exposure prevalence and estimates of relative risk derived from recently published meta-analyses. Population attributable fractions (PAFs) for individual risk factors ranged from 0.40 to 19.93%. Because of differences in the prevalence of exposures, the PAFs associated with several of the risk factors varied greatly by geographical region. Exposure to the selected risk factors appeared to explain a much larger proportion of lung cancer cases in never-smokers in China than in Europe and North America. Our results demonstrate the geographic variability of the epidemiology of lung cancer in never-smokers and highlight the need for further research in this area, particularly in Europe and North America.

Social distancing and mask-wearing could avoid recurrent stay-at-home restrictions during COVID-19 respiratory pandemic in New York City.

Stay-at-home restrictions such as closure of non-essential businesses were effective at reducing SARS-CoV-2 transmission in New York City (NYC) in the spring of 2020. Relaxation of these restrictions was desirable for resuming economic and social activities, but could only occur in conjunction with measures to mitigate the expected resurgence of new infections, in particular social distancing and mask-wearing. We projected the impact of individuals' adherence to social distancing and mask-wearing on the duration, frequency, and recurrence of stay-at-home restrictions in NYC. We applied a stochastic discrete time-series model to simulate community transmission and household secondary transmission in NYC. The model was calibrated to hospitalizations, ICU admissions, and COVID-attributable deaths over March-July 2020 after accounting for the distribution of age and chronic health conditions in NYC. We projected daily new infections and hospitalizations up to May 31, 2021 under the different levels of adherence to social distancing and mask-wearing after relaxation of stay-at-home restrictions. We assumed that the relaxation of stay-at-home policies would occur in the context of adaptive reopening, where a new hospitalization rate of ≥ 2 per 100,000 residents would trigger reinstatement of stay-at-home restrictions while a new hospitalization rate of ≤ 0.8 per 100,000 residents would trigger relaxation of stay-at-home restrictions. Without social distancing and mask-wearing, simulated relaxation of stay-at-home restrictions led to epidemic resurgence and necessary reinstatement of stay-at-home restrictions within 42 days. NYC would have stayed fully open for 26% of the time until May 31, 2021, alternating reinstatement and relaxation of stay-at-home restrictions in four cycles. At a low (50%) level of adherence to mask-wearing, NYC would have needed to implement stay-at-home restrictions between 8% and 32% of the time depending on individual adherence to social distancing. At moderate to high levels of adherence to mask-wearing without social distancing, NYC would have needed to implement stay-at-home restrictions. In threshold analyses, avoiding reinstatement of stay-at-home restrictions required a minimum of 60% adherence to mask-wearing at 50% adherence to social distancing. With low adherence to mask-wearing and social distancing, reinstatement of stay-at-home restrictions in NYC was inevitable. High levels of adherence to social distancing and mask-wearing could have attributed to avoiding recurrent surges without reinstatement of stay-at-home restrictions.

Heterogeneity in Current Cigarette Smoking among Hispanic/Latino Heritage Groups in New York City, 2003-2016.

Objectives: We assessed differences in trends, prevalence, and sociodemographic correlates of current smoking among several predominant Hispanic/Latino heritage groups (Puerto Ricans, Dominicans, Central and South Americans, and other Hispanic/Latinos) in New York City (NYC). We additionally compared current smoking prevalence between heritage groups and non-Hispanic/Latino Whites. Design and Methods: Data from the Community Health Survey, a representative, dual-frame landline/cellphone survey, were analyzed to assess age-adjusted prevalence of current smoking, separately among heritage groups from 2003-2016. Logistic regression was used to estimate odds ratios and 95% CIs for current smoking by Hispanic/Latino heritage group relative to non-Hispanic/Latino Whites in combined 2012-2016 data. Logistic regression was also used to examine correlates of smoking among each heritage group, separately. Results: Between 2003-2016, current smoking prevalence decreased among all Hispanic/Latinos heritage groups except Puerto Ricans, who had the highest smoking prevalence among all groups examined. Sex-stratified trend analyses showed decreases among all groups except Puerto Rican and other Hispanic/Latino males. In multivariable-adjusted models, relative to non-Hispanic/Latino Whites, there was no association with current smoking among Puerto Ricans, but odds of smoking were lower among all other heritage groups. Female sex was inversely associated with current smoking among all heritage groups, and acculturation was positively associated with smoking among all groups except Central/South Americans. Lower educational attainment was strongly associated with smoking among Puerto Ricans. Conclusions: Lack of progress in reducing smoking among Puerto Ricans in NYC is concerning. Opportunities for cultural, sex-specific, and other targeted outreach to this community should be explored.

Demographic and psychological moderators of the relationship between neighborhood cigarette advertising and current smoking in New York City.

BACKGROUND: Tobacco advertising in retailers influences smoking, but little research has examined how this relationship differs among population subgroups. This study merged data on neighborhood cigarette advertising with geocoded survey data to assess the association between advertising prevalence and current smoking among New York City (NYC) residents, and whether demographic and psychological characteristics moderate this relationship. METHODS: Audit data from a stratified, random sample of 796 NYC tobacco retailers generated neighborhood prevalence estimates of cigarette advertising, which were linked with unweighted 2017 NYC Community Health Survey data (n = 7837 adult respondents with residential geocodes). Multilevel regression estimated adjusted odds ratios (aOR) of current smoking by level of neighborhood cigarette advertising (quartiles). Interactions assessed differences in this relationship by demographic characteristics and current depression (analyses conducted in 2019). RESULTS: There was no main effect of advertising on smoking status or significant interactions with demographic variables, but current depression was an effect modifier (p = 0.045). Cigarette advertising was associated with current smoking among those with current depression (p = 0.023), not those without (p = 0.920). Specifically, respondents with depression who resided in neighborhoods in the highest quartile for cigarette advertising prevalence had higher odds of current smoking, compared to those living in the lowest advertising quartile [aOR: 1.72 (1.04, 2.86)]. CONCLUSION: Retail cigarette advertising may serve as an environmental cue to smoke among adults with depression. Efforts to restrict or counteract this practice, such as the development of community-level public health interventions and counter-marketing programs, may particularly benefit those with depression and, perhaps, other mental health disorders.

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

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

Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study.

Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer.

Alcohol Consumption and Urinary Estrogens and Estrogen Metabolites in Premenopausal Women.

In a cross-sectional analysis, we evaluated the associations of usual total alcohol and wine intake with a comprehensive profile of mid-luteal phase urinary estrogens and estrogen metabolites (referred to jointly as EM) in a sample of 603 premenopausal women participating in the Nurses' Health Study II (NHSII). A total of 15 individual EM (pmol/mg creatinine) were measured by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method with high accuracy and reproducibility. We used linear mixed models to calculate the adjusted geometric means of individual EM, EM grouped by metabolic pathways, and pathway ratios by category of alcohol intake with non-drinkers of alcohol as the referent. Total alcohol intake was not associated with total EM but was positively associated with estradiol (26% higher among women consuming >15 g/day vs. non-drinkers; P trend = 0.03). Wine consumption was positively associated with a number of EM measures including estradiol (22% higher among women consuming ≥ 5 drinks/week vs. non-drinkers, P trend < 0.0001). In conclusion, the total alcohol intake was positively and significantly associated with urinary estradiol levels. Some differences in urinary estrogen metabolites were observed with wine drinking, when compared with non-drinkers. This study strengthens the evidence that alcohol consumption might play a role in breast cancer and other estrogen-related conditions. Additional studies of premenopausal women are needed to further explore the association of alcohol, particularly the specific types of alcohol, on patterns of estrogen metabolism in blood, urine, and tissue.

The effects of sleep and light at night on melatonin in adolescents.

OBJECTIVE: The circadian hormone melatonin has wide-reaching effects on human physiology. In adolescents, the impact of nighttime light exposure and other modifiable behavioral factors on melatonin levels is poorly understood. DESIGN: We cross-sectionally examined the influence of nighttime behaviors on melatonin levels in 100 adolescents (average age: 15.7; 55 female, 45 male), who completed a self-administered questionnaire and provided a first morning urine sample to assay for urinary 6-sulfatoxymelatonin (aMT6s) levels. We used mixed-effects regression models to test for differences in aMT6s levels by categories of covariates. RESULTS: Self-reported sleep duration, ambient light levels during sleep, and use of electronics after turning off lights did not significantly predict aMT6s levels. Compared to those who reported weekend bedtimes before 11 pm, urinary aMT6s levels were significantly lower among participants reporting weekend bedtimes after midnight (52.5 vs. 38.0 ng/mg creatinine, P trend=0.007). Sleep interruption also appeared to be significantly associated with lower urinary aMT6s levels, but only if lights were turned on during sleep interruption (43.0 ng/mg creatinine for participants with sleep interruption but not turning lights on, vs. 24.6 ng/mg creatinine for participants reporting that they turned on the light when their sleep was interrupted P difference=0.032). CONCLUSIONS: Our study suggests that self-reported sleep-related behaviors have little to no effect on adolescent circadian systems, though larger studies are needed to confirm our findings.

Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women.

BACKGROUND: Prior studies have found weak inverse associations between breast cancer and caffeine and coffee intake, possibly mediated through their effects on sex hormones. METHODS: High-performance liquid chromatography/tandem mass spectrometry was used to quantify levels of 15 individual estrogens and estrogen metabolites (EM) among 587 premenopausal women in the Nurses' Health Study II with mid-luteal phase urine samples and caffeine, coffee, and/or tea intakes from self-reported food frequency questionnaires. Multivariate linear mixed models were used to estimate geometric means of individual EM, pathways, and ratios by intake categories, and P values for tests of linear trend. RESULTS: Compared with women in the lowest quartile of caffeine consumption, those in the top quartile had higher urinary concentrations of 16α-hydroxyestrone (28% difference; Ptrend = 0.01) and 16-epiestriol (13% difference; Ptrend = 0.04), and a decreased parent estrogens/2-, 4-, 16-pathway ratio (Ptrend = 0.03). Coffee intake was associated with higher 2-catechols, including 2-hydroxyestradiol (57% difference, ≥4 cups/day vs. ≤6 cups/week; Ptrend = 0.001) and 2-hydroxyestrone (52% difference; Ptrend = 0.001), and several ratio measures. Decaffeinated coffee was not associated with 2-pathway metabolism, but women in the highest (vs. lowest) category of intake (≥2 cups/day vs. ≤1-3 cups/month) had significantly lower levels of two 16-pathway metabolites, estriol (25% difference; Ptrend = 0.01) and 17-epiestriol (48% difference; Ptrend = 0.0004). Tea intake was positively associated with 17-epiestriol (52% difference; Ptrend = 0.01). CONCLUSION: Caffeine and coffee intake were both associated with profiles of estrogen metabolism in premenopausal women. IMPACT: Consumption of caffeine and coffee may alter patterns of premenopausal estrogen metabolism.