Temporal trends in phthalate metabolite exposure of girls in the United States across sociodemographic factors and intersectional social identities: National Health and Nutrition Examination Survey (NHANES) 2001-2018.

BACKGROUND: Exposure to phthalates during the pubertal window is linked to an increased risk of chronic diseases. Understanding temporal trends in exposure can inform public health initiatives. OBJECTIVE: Characterize temporal trends in phthalate metabolite levels in adolescent girls overall and by sociodemographic characteristics. METHODS: We used the cross-sectional data from each cycle of NHANES from years 2001-2018. We included participants aged 8-14 years who had at least one urinary measurement of the selected 12 phthalate metabolites within the study period (n = 2063). We used multivariable linear regression to assess temporal trends for selected individual phthalate metabolite concentrations (ng/ml) and source groupings of parent metabolites (sum low and high molecular weight phthalates; ∑LMW and ∑HMW), overall and by sociodemographic characteristics (race/ethnicity), nativity, socioeconomic status (SES), intersection of race/ethnicity-SES) to assess for modification. RESULTS: Overall, levels of ∑HMW and ∑LMW declined between 2001 and 2018; however, only ∑LMW consistently differed by all sociodemographic characteristics. Trends in ∑LMW concentration were significantly higher across all racial/ethnic groups, ranging from an average of 35% (Other Hispanic) to 65% (Mexican American and non-Hispanic Black) higher than non-Hispanic White (all p-values <0.0001). Compared to non-Hispanic White, a significant decrease in MiBP concentrations was observed for non-Hispanic Black (15% decrease ßSpline = -0.16, p < 0.0001) and Other Hispanic (28% decrease, ßSpline = -0.33, p = 0.01) in 2011-2018 versus 2001-2010. Summary and individual LMW metabolite phthalate concentrations were 11%-49% higher among girls with low vs. high SES. LMW metabolites MBP and MiBP were on average 22% and 35% higher, respectively, among foreign-born vs. U.S.-born girls. Compared to non-Hispanic Whites, all racial/ethnic groups had statistically significant higher trends in ∑LMW concentrations irrespective of SES. SIGNIFICANCE: Girls identifying with a historically disadvantaged racial/ethnic groups exhibited elevated ∑LMW concentrations irrespective of SES; suggesting the need for targeted interventions to mitigate exposure among the most historically disadvantaged strata.

Exposure to polycyclic aromatic hydrocarbons during pregnancy and breast tissue composition in adolescent daughters and their mothers: a prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers. METHODS: We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother-daughter dyads (recruited 1998-2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters (n = 186) and mothers (n = 175) reached ages 11-20 and 29-55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS. RESULTS: No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content (ßdaughters = 0.42, 95% CI = 0.15-0.68; ßmothers = 0.32, 95% CI = 0.05-0.61) and higher optical index (ßdaughters = 0.38, 95% CI = 0.12-0.64; ßmothers = 0.38, 95% CI = 0.12-0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05). CONCLUSIONS: Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations.

Identifying environmental exposure profiles associated with timing of menarche: A two-step machine learning approach to examine multiple environmental exposures.

BACKGROUND: Variation in the timing of menarche has been linked with adverse health outcomes in later life. There is evidence that exposure to hormonally active agents (or endocrine disrupting chemicals; EDCs) during childhood may play a role in accelerating or delaying menarche. The goal of this study was to generate hypotheses on the relationship between exposure to multiple EDCs and timing of menarche by applying a two-stage machine learning approach. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) for years 2005-2008. Data were analyzed for 229 female participants 12-16 years of age who had blood and urine biomarker measures of 41 environmental exposures, all with >70% above limit of detection, in seven classes of chemicals. We modeled risk for earlier menarche (<12 years of age vs older) with exposure biomarkers. We applied a two-stage approach consisting of a random forest (RF) to identify important exposure combinations associated with timing of menarche followed by multivariable modified Poisson regression to quantify associations between exposure profiles ("combinations") and timing of menarche. RESULTS: RF identified urinary concentrations of monoethylhexyl phthalate (MEHP) as the most important feature in partitioning girls into homogenous subgroups followed by bisphenol A (BPA) and 2,4-dichlorophenol (2,4-DCP). In this first stage, we identified 11 distinct exposure biomarker profiles, containing five different classes of EDCs associated with earlier menarche. MEHP appeared in all 11 exposure biomarker profiles and phenols appeared in five. Using these profiles in the second-stage of analysis, we found a relationship between lower MEHP and earlier menarche (MEHP ≤ 2.36 ng/mL vs >2.36 ng/mL: adjusted PR = 1.36, 95% CI: 1.02, 1.80). Combinations of lower MEHP with benzophenone-3, 2,4-DCP, and BPA had similar associations with earlier menarche, though slightly weaker in those smaller subgroups. For girls not having lower MEHP, exposure profiles included other biomarkers (BPA, enterodiol, monobenzyl phthalate, triclosan, and 1-hydroxypyrene); these showed largely null associations in the second-stage analysis. Adjustment for covariates did not materially change the estimates or CIs of these models. We observed weak or null effect estimates for some exposure biomarker profiles and relevant profiles consisted of no more than two EDCs, possibly due to small sample sizes in subgroups. CONCLUSION: A two-stage approach incorporating machine learning was able to identify interpretable combinations of biomarkers in relation to timing of menarche; these should be further explored in prospective studies. Machine learning methods can serve as a valuable tool to identify patterns within data and generate hypotheses that can be investigated within future, targeted analyses.

Associations of prenatal exposure to polycyclic aromatic hydrocarbons with pubertal timing and body composition in adolescent girls: Implications for breast cancer risk.

BACKGROUND: While animal data support an association between prenatal exposure to endocrine disrupting chemicals (EDCs) and altered mammary gland development and tumorigenesis, epidemiologic studies have only considered a few classes of EDCs in association with pubertal growth and development in girls. Polycyclic aromatic hydrocarbons (PAH) are a class of EDCs that have not been rigorously evaluated in terms of prenatal exposure and pubertal growth and development in girls. OBJECTIVE: In a New York City birth cohort of Black and Hispanic girls (n = 196; recruited 1998-2006), we examined associations of prenatal PAH exposure with self-reported age at growth spurt onset, breast development onset and menarche, and clinical measures of adolescent body composition including body mass index, waist-to-hip ratio, and body fat measured at ages 11-20 years. METHODS: We measured prenatal exposure to PAH using personal air monitoring data collected from backpacks worn by mothers during the third trimester of pregnancy (data available for all 196 girls) and biomarkers of benzo[α]pyrene-DNA adducts in umbilical cord blood (data available for 106 girls). We examined associations of prenatal PAH with the timing of pubertal milestones and adolescent body composition (11-20 years) using multivariable linear regression models adjusted for race/ethnicity, household public assistance status at birth, and age at outcome assessment. We also fit models further adjusted for potential mediators, including birthweight and childhood body size (BMI-for-age z-score measured at 6-8 years). RESULTS: Girls in the highest versus lowest tertile of ambient exposure to PAH, based on a summary measure of eight carcinogenic higher-molecular weight non-volatile PAH compounds (Σ8 PAH), had a 0.90 year delay in growth spurt onset (95% confidence interval (CI) = 0.25, 1.55; n = 196), a 0.35 year delay in breast development onset (95% CI = -0.26, 0.95; n = 193), and a 0.59 year delay in menarche (95% CI = 0.06, 1.11; n = 191) in models adjusted for race/ethnicity and household public assistance at birth. The statistically significant associations for age at growth spurt onset and menarche were not impacted by adjustment for birthweight or childhood body size. No differences in BMI-for-age z-score, waist-to-hip ratio, or percent body fat were found between girls in the highest versus lowest tertile of ambient Σ8 PAH. Results were similar when we evaluated benzo[α]pyrene-DNA adduct levels. DISCUSSION: Our results suggest that prenatal exposure to PAH might delay pubertal milestones in girls, but findings need to be replicated in other cohorts using prospectively collected data on pubertal outcomes.

Environmental exposures and breast cancer risk in the context of underlying susceptibility: A systematic review of the epidemiological literature.

BACKGROUND: The evidence evaluating environmental chemical exposures (ECE) and breast cancer (BC) risk is heterogeneous which may stem in part as few studies measure ECE during key BC windows of susceptibility (WOS). Another possibility may be that most BC studies are skewed towards individuals at average risk, which may limit the ability to detect signals from ECE. OBJECTIVES: We reviewed the literature on ECE and BC focusing on three types of studies or subgroup analyses based on higher absolute BC risk: BC family history (Type 1); early onset BC (Type 2); and/or genetic susceptibility (Type 3). METHODS: We systematically searched the PubMed database to identify epidemiologic studies examining ECE and BC risk published through June 1, 2019. RESULTS: We identified 100 publications in 56 unique epidemiologic studies. Of these 56 studies, only 2 (3.6%) were enriched with BC family history and only 11% of studies (6/56) were specifically enriched with early onset cases. 80% of the publications from these 8 enriched studies (Type 1: 8/10 publications; Type 2: 8/10 publications) supported a statistically significant association between ECE and BC risk including studies of PAH, indoor cooking, NO2, DDT; PCBs, PFOSA; metals; personal care products; and occupational exposure to industrial dyes. 74% of Type 3 publications (20/27) supported statistically significant associations for PAHs, traffic-related air pollution, PCBs, phthalates, and PFOSAs in subgroups of women with greater genetic susceptibility due to variants in carcinogen metabolism, DNA repair, oxidative stress, cellular apoptosis and tumor suppressor genes. DISCUSSION: Studies enriched for women at higher BC risk through family history, younger age of onset and/or genetic susceptibility consistently support an association between an ECE and BC risk. In addition to measuring exposures during WOS, designing studies that are enriched with women at higher absolute risk are necessary to robustly measure the role of ECE on BC risk.

Gestational diabetes, type II diabetes, and mammographic breast density in a U.S. racially diverse population screened for breast cancer.

PURPOSE: Type II diabetes mellitus (T2DM) has consistently been associated with an increased risk of breast cancer, but the association of gestational diabetes mellitus (GDM) with breast cancer is less clear. T2DM and GDM may influence breast cancer risk through mammographic breast density, a strong risk factor for breast cancer. We examined whether T2DM and GDM are associated with higher mammographic breast density in a largely racial/ethnic minority sample. METHODS: We collected digital mammograms, anthropometric measures, and interview data from 511 racially diverse women recruited during screening mammography appointments between 2012 and 2016 (mean age 51 years; 70% Hispanic). We examined the associations of self-reported GDM, T2DM, and medication use (metformin and insulin) with mammographic breast density, measured as percent and area of dense tissue using Cumulus software. RESULTS: In multivariable linear regression models, history of T2DM and/or GDM and length of time since diagnosis were not associated with percent density or dense breast area, either before or after adjustment for current BMI. Use of metformin in diabetic women was associated with lower percent density (ß = - 5.73, 95% CI - 10.27, - 1.19), only before adjusting for BMI. These associations were not modified by menopausal status. CONCLUSIONS: Our results do not support associations between T2DM and/or GDM and higher amount of mammographically dense breast tissue, suggesting that the mechanism linking diabetes with breast cancer risk may not include mammographic breast density in midlife.

The metabolic syndrome and mammographic breast density in a racially diverse and predominantly immigrant sample of women.

PURPOSE: The metabolic syndrome [MetS, clustering of elevated blood pressure, triglycerides and glucose, reduced high-density lipoprotein cholesterol (HDL-C), abdominal obesity] has been associated with increased breast cancer risk, but less is known about its association with mammographic breast density, a strong risk factor for breast cancer. METHODS: We collected data on risk factors, body size, and blood pressure via in-person interviews and examinations and measured glucose, triglycerides, and HDL-C from dried blood spots from women recruited through a mammography screening clinic (n = 373; 68 % Hispanic, 17 % African-American, 63 % foreign born). We performed linear regression models to examine the associations of each MetS component and the MetS cluster (≥3 components) with percent density and dense breast area, measured using a computer-assisted technique and Cumulus software. RESULTS: About 45 % of women had the MetS, with the prevalence of the individual components ranging from 68 % for abdominal obesity to 33 % for elevated triglycerides. The prevalence of the MetS increased with higher body mass index (BMI) and postmenopausal status, but did not vary substantially by ethnicity, immigrant generational status, parity, age at menarche, or alcohol consumption. Low HDL-C (<50 mg/dL), but not the MetS cluster or the other MetS components, was associated with larger dense breast area after adjusting for age, BMI, fasting time, and educational attainment (ß = 8.77, 95 % CI 2.39, 15.14). The MetS and its individual components were not associated with BMI-adjusted percent density. CONCLUSIONS: HDL-C alone may have an influence on dense breast tissue that is independent of BMI, and may be in the same direction as its association with breast cancer risk.

Identifying critical windows of prenatal phenol, paraben, and pesticide exposure and child neurodevelopment: Findings from a prospective cohort study.

BACKGROUND: This study aimed to investigate how exposure to a mixture of endocrine disrupting chemicals (EDCs) during two points in pregnancy affects early childhood neurodevelopment. METHODS: We analyzed publicly-available data from a high-risk cohort of mothers and their children (2007-2014) that measured six EDCs including methyl-, ethyl- and propyl parabens (MEPB, ETPB, PRPB), Bisphenol-A (BPA), 3,5,6-trichloro-2-pyridinol (TCPy), 3-phenoxybenzoic acid (3-PBA) in prenatal urine samples during the second and third trimesters. Neurodevelopmental scores were assessed using Mullen Scales of Early Learning (MSEL) at age 3. We used mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR) to investigate the association between trimester-specific co-exposure to the six EDCs and MSEL scores at age 3, stratified by sex. RESULTS: The analysis included 130 children. For females, the relationship between BPA and 3PBA with MSEL score varied between the two trimesters. In the second trimester, effect estimates for BPA were null but inversely correlated with MSEL score in the third trimester. 3PBA had a negative relationship with MSEL in the second trimester and positive correlation in the third trimester. For males, effect estimates for all EDCs were in opposing directions across trimesters. MFVB-LKMR analysis identified significant two-way interaction between EDCs for MSEL scores in both trimesters. For example, in females, the MSEL scores associated with increased exposure to TCPy were 1.75 units (95%credible interval -0.04, -3.47) lower in the 2nd trimester and 4.61 (95%CI -3.39, -5.84) lower in the third trimester when PRPB was fixed at the 75th percentile compared to when PRPB was fixed at the 25th percentile. CONCLUSION: Our study provides evidence that timing of EDC exposure within the prenatal period may impact neurodevelopmental outcomes in children. More of these varying effects were identified among females. Future research is needed to explore EDC mixtures and the timing of exposure during pregnancy to enhance our understanding of how these chemicals impact child health.

Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.

The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.

Is there a role for routine screening MRI in women with LCIS?

Women with lobular carcinoma in situ (LCIS) have an elevated breast cancer risk, yet the benefit of MRI screening is unclear. We examined cancer detection rates with mammography alone versus mammography plus MRI in this high-risk population. From a prospectively maintained, single-institution database, we identified 776 patients diagnosed with LCIS after the adoption of screening MRI in April 1999. In addition to annual mammography and breast exam, MRI was used at the discretion of the physician and patient. Kaplan-Meier methods and landmark analyses at 1, 2, and 3 years following LCIS diagnosis were performed to compare rates of cancer detection with or without MRI. MRI screening was performed in 455 (59 %) patients (median, 3/patient). Median time from LCIS diagnosis to first MRI was 9 months (range 0.3-137 months). Patients undergoing MRI were younger (p < 0.0001), premenopausal (p < 0.0001), and more likely to have ≥1 first-degree relative with breast cancer (p = 0.009). At a median follow-up of 58 months, 98/776 (13 %) patients developed cancer. The crude cancer detection rate in both screening groups was 13 %. MRI was not associated with earlier stage, smaller size, or node negativity. Landmark analyses at 1, 2, and 3 years after LCIS diagnosis failed to demonstrate increased cancer detection rates among women having MRI (p = 0.23, 0.26, and 0.13, respectively). Although a diagnosis of LCIS remains a significant risk factor for breast cancer, the routine use of MRI does not result in increased cancer detection rates (short-term), nor does it result in earlier stage at diagnosis, illustrating the importance of defining optimal screening strategies for high-risk patients based on tumor biology rather than numerical risk.

Real-World Treatment Patterns and Outcomes of First-Line Immunotherapy Among Patients With Advanced Nonsquamous NSCLC Harboring BRAF, MET, or HER2 Alterations.

Introduction: Data on utilization and clinical outcomes of programmed cell death protein or programmed death-ligand 1 (PD-[L]1) inhibitors in NSCLC with uncommon oncogenic alterations is limited. Methods: This retrospective study used a deidentified U.S. nationwide clinicogenomic database to select patients with advanced nonsquamous NSCLC without EGFR, ALK, or ROS1 alterations, diagnosed from January 1, 2016 to September 30, 2020, who initiated first-line therapy. Our objectives were to summarize characteristics and treatment patterns for patients with four little-studied genomic alterations or driver-negative NSCLC. We estimated Kaplan-Meier real-world time on treatment (rwTOT) and time to next treatment for patients receiving PD-(L)1 inhibitors. The data cutoff was September 30, 2021. Results: Of the 3971 eligible patients, 84 (2%) had NSCLC with BRAF V600E mutation, 117 (3%) had MET exon 14 skipping mutation, 130 (3%) had MET amplification, 91 (2%) had ERBB2 activation mutation, and 691 patients (17%) had driver-negative NSCLC. Patient characteristics differed among cohorts as expected. The most common first-line regimen in each cohort was a PD-(L)1 inhibitor as monotherapy or in combination with chemotherapy. The median rwTOT with anti-PD-(L)1 monotherapy was 4.6 months in the driver-negative cohort and ranged from 2.9 months (ERBB2 mutation) to 7.6 months (BRAF V600E mutation). The median rwTOT with anti-PD-(L)1-chemotherapy combination was 5.2 months in the driver-negative cohort and 6 months in all but the BRAF V600E cohort (17.5 mo). The patterns of real-world time to next treatment results were similar. Conclusions: Substantial use of anti-PD-(L)1 therapy and associated clinical outcomes are consistent with previous real-world findings and suggest no detriment from PD-(L)1 inhibitors for advanced nonsquamous NSCLC harboring one of these four genomic alterations relative to driver-negative NSCLC.

The Impact of Race on Perioperative and Patient-Reported Outcomes following Autologous Breast Reconstruction.

BACKGROUND: Racial disparities are evident in multiple aspects of the perioperative care of breast cancer patients, but data examining whether such differences translate to clinical and patient-reported outcomes are limited. This study examined the impact of race on perioperative outcomes in autologous breast reconstruction. METHODS: A retrospective cohort study including all breast cancer patients who underwent immediate autologous breast reconstruction at a single institution from 2010 to 2017 was conducted. Self-reported race was used to classify patients into three groups: white, African American, and other. The primary and secondary endpoints were occurrence of any major complications within 30 days of surgery and patient-reported outcomes (measured with the BREAST-Q), respectively. Regression models were constructed to identify factors associated with the outcomes. RESULTS: Overall, 404 patients, including 259 white (64 percent), 63 African American (16 percent), and 82 patients from other minority groups (20 percent), were included. African American patients had a significantly higher proportion of preoperative comorbidities. Postoperatively, African American patients had a higher incidence of 30-day major complications (p = 0.004) and were more likely to return to the operating room (p = 0.006). Univariable analyses examining complications demonstrated that race was the only factor associated with 30-day major complications (p = 0.001). Patient-reported outcomes were not statistically different at each time point through 3 years postoperatively. CONCLUSIONS: African American patients continue to present with increased comorbidities and may be more likely to experience major complications following immediate autologous breast reconstruction. However, patient-reported satisfaction or physical well-being outcomes may not differ between groups. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

A comparison of various methods for measuring breast density and breast tissue composition in adolescent girls and women.

This study compared different approaches to measuring breast density and breast tissue composition (BTC) in adolescent girls (n = 42, aged 14-16 years) and their mothers (n = 39, aged 36-61 years) from a cohort in Santiago, Chile. Optical spectroscopy (OS) was used to measure collagen, water, and lipid concentrations, which were combined into a percent breast density index (%BDI). A clinical dual-energy X-ray absorptiometry (DXA) system calibrated to measure breast density provided percent fibroglandular volume (%FGV) from manually delineated images. After digitizing mammogram films, the percent mammographic breast density (%MBD) was measured using computer-assisted software. Partial correlation coefficients (rpartial) were used to evaluate associations between breast density measures and BTC from these three different measurement approaches, adjusting for age and body mass index. %BDI from OS was associated with %FGV from DXA in adolescent girls (rpartial = 0.46, p-value = 0.003), but not in mothers (rpartial = 0.17, p-value = 0.32). In mothers, %FGV from DXA was associated with %MBD from mammograms (rpartial = 0.60, p-value < 0.001). These findings suggest that data from OS, DXA, and mammograms provide related but distinct information about breast density and BTC. Future studies should explore how the information provided by these different devices can be used for breast cancer risk prediction in cohorts of adolescent girls and women.

Breast Tissue Composition-Why It Matters and How Can We Measure It More Accurately in Epidemiology Studies.

Early-life body size has been consistently associated with breast cancer risk. The direction of the association changes over time, with high birth weight, smaller adolescent body size, and adult weight gain all increasing breast cancer risk. There is also a clear positive association between larger body size and increased breast adipose tissue measured by mammograms, but less is known about how body size changes across life stages affect stromal and epithelial breast tissue. Using breast tissue slides from women with benign breast disease, Oh and colleagues applied machine learning methods to evaluate body size across the life course and adipose, epithelial, and stromal tissue concentrations in adulthood. They found consistent patterns for higher adipose and lower stromal tissue concentrations with larger childhood and adult body size at age 18 years. They reported lower levels of epithelial tissue with larger body size at 18 years, but not at other time periods. Additional studies examining how body size at different life stages may affect breast tissue composition will be important. Noninvasive methods that can provide measures of breast tissue composition may offer potential ways forward to ensure generalizability, and repeated measurements by life stage.See related article by Oh et al., p. 608.

Goal-directed fluid therapy in autologous breast reconstruction results in less fluid and more vasopressor administration without outcome compromise.

OBJECTIVE: Aggressive or restricted perioperative fluid management has been shown to increase complications in patients undergoing microsurgery. Goal-directed fluid therapy (GDFT) aims to administer fluid, vasoactive agents, and inotropes according to each patient's hemodynamic indices. This study assesses GDFT impact on perioperative outcomes of autologous breast reconstruction (ABR) patients, as there remains a gap in management understanding. We hypothesize that GDFT will have lower fluid administration and equivocal outcomes compared to patients not on GDFT. METHODS: A single-center retrospective review was conducted on ABR patients from January 2010-April 2017. An enhanced recovery after surgery (ERAS) using GDFT was implemented in April 2015. With GDFT, patients were administered intraoperative fluids and vasoactive agents according to hemodynamic indices. Patients prior to April 2015 were included in the pre-ERAS cohort. Primary outcomes included the amount and rate of fluid delivery, urine output (UOP), vasopressor administration, major (i.e., flap failure) and minor (i.e., seroma) complications, and length of stay (LOS). RESULTS: Overall, 777 patients underwent ABR (ERAS: 312 and pre-ERAS: 465). ERAS patients received significantly less total fluid volume (ERAS median: 3750 mL [IQR: 3000-4500 mL]; pre-ERAS median: 5000 mL [IQR 4000-6400 mL]; and p<0.001), had lower UOP, were more likely to receive vasopressor agents (47% vs 35% and p<0.001), and had lower LOS (ERAS: 4 days [4-5]; pre-ERAS: 5 [4-6]; and p<0.001) as compared to pre-ERAS patients. Complications did not differ between cohorts. CONCLUSIONS: GDFT, as part of ERAS, and the prudent use of vasopressors were found to be safe and did not increase morbidity in ABR patients. GDFT provides individualized perioperative care to the ABR patient.

Machine Learning Within Studies of Early-Life Environmental Exposures and Child Health: Review of the Current Literature and Discussion of Next Steps.

PURPOSE OF REVIEW: The goal of this article is to review the use of machine learning (ML) within studies of environmental exposures and children's health, identify common themes across studies, and provide recommendations to advance their use in research and practice. RECENT FINDINGS: We identified 42 articles reporting upon the use of ML within studies of environmental exposures and children's health between 2017 and 2019. The common themes among the articles were analysis of mixture data, exposure prediction, disease prediction and forecasting, analysis of complex data, and causal inference. With the increasing complexity of environmental health data, we anticipate greater use of ML to address the challenges that cannot be handled by traditional analytics. In order for these methods to beneficially impact public health, the ML techniques we use need to be appropriate for our study questions, rigorously evaluated and reported in a way that can be critically assessed by the scientific community.

Predictors of Breast Cancer Worry in a Hispanic and Predominantly Immigrant Mammography Screening Population.

OBJECTIVE: Worry about developing breast cancer (BC) has been associated with participation in screening and genetic testing and with follow-up of abnormal screening results. Little is known about the scope and predictors of BC worry in Hispanic and immigrant populations. METHODS: We collected in-person interview data from 250 self-identified Hispanic women recruited from an urban mammography facility (average age 50.4 years; 82% foreign-born). Women reported whether they worried about developing breast cancer rarely/never (low worry), sometimes (moderate worry), or often/all the time (high worry). We examined whether sociocultural and psychological factors (e.g., acculturation, education, perceived risk), and risk factors and objective risk for BC (e.g., family history, Gail model 5-year risk estimates, parity) predicted BC worry using multinomial and logistic regression. RESULTS: In multivariable models, women who perceived higher absolute BC risk (odds ratio, 1.66 [95% confidence interval, 1.28-2.14] for a one-unit increase in perceived lifetime risk) and comparative BC risk (e.g., odds ratio, 2.73, 95% confidence interval, 1.23-6.06) were more likely to report high BC worry than moderate or low BC worry. There were no associations between BC worry and indicators of objective risk or acculturation. CONCLUSIONS: In Hispanic women undergoing screening mammography, higher perceptions of BC risk, in both absolute and comparative terms, were associated independently with high BC worry, and were stronger predictors of BC worry than indicators of objective BC risk, including family history, mammographic density, and personal BC risk estimates.

Is Enhanced Recovery the New Standard of Care in Microsurgical Breast Reconstruction?

BACKGROUND: At present, there are limited data available regarding the use and feasibility of enhanced recovery pathways for patients undergoing microsurgical breast reconstruction. The authors sought to assess patient outcomes before and after the introduction of an enhanced recovery pathway that was adopted at a single cancer center. METHODS: A multidisciplinary enhanced recovery pathway was developed for patients undergoing deep inferior epigastric perforator or free transverse rectus abdominis myocutaneous flap breast reconstruction. Core elements of the enhanced recovery pathway included substituting intravenous patient-controlled analgesia with ketorolac and transversus abdominis plane blocks using liposomal bupivacaine, as well as intraoperative goal-directed fluid management. Patients who underwent surgery between April and August of 2015 using the enhanced recovery pathway were compared with a historical control cohort. The primary endpoints were hospital length of stay and total postoperative opioid consumption. RESULTS: In total, 91 consecutive patients were analyzed (enhanced recovery pathway, n = 42; pre-enhanced recovery pathway, n = 49). Mean hospital length of stay was significantly shorter in the enhanced recovery pathway group than in the pre-enhanced recovery pathway group (4.0 days versus 5.0 days; p < 0.0001). Total postoperative morphine equivalent consumption was also lower in the enhanced recovery pathway group (46.0 mg versus 70.5 mg; p = 0.003). There was no difference in the incidence of 30-day complications between the groups (p = 0.6). CONCLUSION: The adoption of an enhanced recovery pathway for deep inferior epigastric perforator and transverse rectus abdominis myocutaneous flap reconstruction by multiple surgeons significantly decreased opioid consumption and reduced length of stay by 1 day. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Does Checklist Implementation Improve Quantity of Data Transfer: An Observation in Postanesthesia Care Unit (PACU).

BACKGROUND: Omission of patient information in perioperative communication is closely linked to adverse events. Use of checklists to standardize the handoff in the post anesthesia care unit (PACU) has been shown to effectively reduce medical errors. OBJECTIVE: Our study investigates the use of a checklist to improve quantity of data transfer during handoffs in the PACU. DESIGN: A cross-sectional observational study. SETTING: PACU at Memorial Sloan Kettering Cancer Center (MSKCC); June 13, 2016 through July 15, 2016. PATIENTS OTHER PARTICIPANTS: We observed the handoff reports between the nurses, PACU midlevel providers, anesthesia staff, and surgical staff. INTERVENTION: A physical checklist was provided to all anesthesia staff and recommended to adhere to the list at all observed PACU handoffs. MAIN OUTCOME MEASURE: Quantity of reported handoff items during 60 pre- and 60 post-implementation of a checklist. RESULTS: Composite value from both surgical and anesthesia reports showed an increase in the mean report of 8.7 items from pre-implementation period to 10.9 post-implementation. Given that surgical staff reported the mean of 5.9 items pre-implementation and 5.5 items post-implementation without intervention, improvements in anesthesia staff report with intervention improved the overall handoff data transfer. CONCLUSIONS: Using a physical 12-item checklist for PACU handoff increased overall data transfer.

Lobular Carcinoma in Situ: A 29-Year Longitudinal Experience Evaluating Clinicopathologic Features and Breast Cancer Risk.

PURPOSE: The increased breast cancer risk conferred by a diagnosis of lobular carcinoma in situ (LCIS) is poorly understood. Here, we review our 29-year longitudinal experience with LCIS to evaluate factors associated with breast cancer risk. PATIENTS AND METHODS: Patients participating in surveillance after an LCIS diagnosis are observed in a prospectively maintained database. Comparisons were made among women choosing surveillance, with or without chemoprevention, and those undergoing bilateral prophylactic mastectomies between 1980 and 2009. RESULTS: One thousand sixty patients with LCIS without concurrent breast cancer were identified. Median age at LCIS diagnosis was 50 years (range, 27 to 83 years). Fifty-six patients (5%) underwent bilateral prophylactic mastectomy; 1,004 chose surveillance with (n = 173) or without (n = 831) chemoprevention. At a median follow-up of 81 months (range, 6 to 368 months), 150 patients developed 168 breast cancers (63% ipsilateral, 25% contralateral, 12% bilateral), with no dominant histology (ductal carcinoma in situ, 35%; infiltrating ductal carcinoma, 29%; infiltrating lobular carcinoma, 27%; other, 9%). Breast cancer incidence was significantly reduced in women taking chemoprevention (10-year cumulative risk: 7% with chemoprevention; 21% with no chemoprevention; P < .001). In multivariable analysis, chemoprevention was the only clinical factor associated with breast cancer risk (hazard ratio, 0.27; 95% CI, 0.15 to 0.50). In a subgroup nested case-control analysis, volume of disease, which was defined as the ratio of slides with LCIS to total number of slides reviewed, was also associated with breast cancer development (P = .008). CONCLUSION: We observed a 2% annual incidence of breast cancer among women with LCIS. Common clinical factors used for risk prediction, including age and family history, were not associated with breast cancer risk. The lower breast cancer incidence in women opting for chemoprevention highlights the potential for risk reduction in this population.