Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system.

PURPOSE: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. METHODS: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. RESULTS: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. CONCLUSION: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.

Financial hardship differences by LGBTQ+ status among assigned female at birth adolescent and young adult cancer survivors: a mixed methods analysis.

BACKGROUND: Adolescent and young adult (AYA) cancer survivors are at an elevated risk of financial hardship. However, financial hardship among LGBTQ+ AYAs has not been widely explored. Thus, we used qualitative and quantitative survey data from the Horizon Study cohort to assess financial hardship of AYAs by LGBTQ+ status. METHODS: Multivariable logit models, predicted probabilities, average marginal effects or differences in predicted probabilities (AME) and 95% confidence intervals (CI) were used to assess the association of LGBTQ+ status and two components of financial hardship: material and psychological. Qualitative content analysis of an open-ended survey question about financial sacrifices was used to describe the third component of financial hardship, behavioral. RESULTS: Among 1,635 participants, 4.3% self-identified as LGBTQ+. Multivariable logit models controlling for demographic factors revealed that LGBTQ+ AYAs had an 18-percentage point higher probability of experiencing material financial hardship (95%CI 6-30%) and a 14-percentage point higher probability of experiencing psychological financial hardship (95%CI 2-26%) than non-LGBTQ+ AYAs. Controlling for economic factors attenuated the association of LGBTQ+ status with psychological financial hardship (AME = 11%; 95%CI - 1-23%), while the material financial hardship association remained statistically significant (AME = 14%; 95%CI 3-25%). In the qualitative analysis, LGBTQ+ AYAs frequently reported educational changes and costs (e.g., quitting school), unpaid bills and debt (e.g., medical debt, taking on credit card debt), as well as changes in housing and poor housing conditions (e.g., moving into less expensive house). CONCLUSIONS: LGBTQ + targeted and tailored interventions are needed to move toward equity for LGBTQ+ AYAs-an overlooked minority population.

Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system.

PURPOSE: To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. METHODS: Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California. RESULTS: A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. CONCLUSION: Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies.

BACKGROUND: Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. METHODS: To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers. RESULTS: We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer. CONCLUSIONS: Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.

Fertility Preservation and Financial Hardship among Adolescent and Young Adult Women with Cancer.

BACKGROUND: Financial hardship among adolescents and young adults (AYA) with cancer who receive gonadotoxic treatments may be exacerbated by the use of fertility services. This study examined whether AYA women with cancer who used fertility preservation had increased financial hardship. METHODS: AYA women with cancer in North Carolina and California completed a survey in 2018-2019. Cancer-related financial hardship was compared between women who cryopreserved oocytes or embryos for fertility preservation after cancer diagnosis (n = 65) and women who received gonadotoxic treatment and reported discussing fertility with their provider, but did not use fertility preservation (n = 491). Multivariable log-binomial regression was used to estimate prevalence ratios and 95% confidence intervals (CI). RESULTS: Women were a median age of 33 years at diagnosis and 7 years from diagnosis at the time of survey. Women who used fertility preservation were primarily ages 25 to 34 years at diagnosis (65%), non-Hispanic White (72%), and had at least a Bachelor's degree (85%). In adjusted analysis, use of fertility preservation was associated with 1.50 times the prevalence of material financial hardship (95% CI: 1.08-2.09). The magnitude of hardship was also substantially higher among women who used fertility preservation: 12% reported debt of ≥$25,000 versus 5% in the referent group. CONCLUSIONS: This study provides new evidence that cryopreserving oocytes or embryos after cancer diagnosis for future family building is associated with increased financial vulnerability. IMPACT: More legislation that mandates insurance coverage to mitigate hardships stemming from iatrogenic infertility could improve access to fertility preservation for young women with cancer.

Impact of the Affordable Care Act on Colorectal Cancer Incidence and Mortality.

INTRODUCTION: The Patient Protection and Affordable Care Act eliminated cost sharing for preventive services, including colorectal cancer screening for individuals aged 50-75 years with private health insurance. This study examines the impact of the Affordable Care Act's removal of cost sharing for colorectal cancer screening on colorectal cancer incidence and mortality. METHODS: Trends in colorectal cancer incidence and colorectal cancer‒related mortality were modeled among 2,113,283 Kaiser Permanente Northern California members aged ≥50 years between 2003 and 2016 using an interrupted time-series design. As a sensitivity analysis, a controlled analysis utilized a comparison group of members covered with pre‒Affordable Care Act zero cost sharing for colorectal cancer screening. Analyses were performed in 2019 and 2020. RESULTS: The colorectal cancer incidence dropped by 17% around the time the Affordable Care Act was enacted (change in level incidence rate ratio; 95% CI=0.77, 0.90, 2-sided p-value <0.0001), followed by a 3% further decrease per year (95% CI=0.93, 1.00, p=0.05). A similar pattern was observed for colorectal cancer‒related mortality. The controlled results indicated that the elimination of cost sharing for screening due to the Affordable Care Act was associated with greater improvements in colorectal cancer outcomes among members previously covered by health plans with out-of-pocket costs for screening than among those with health plans with zero cost sharing for screening before the Affordable Care Act. CONCLUSIONS: The elimination of cost sharing for colorectal cancer screening due to the Affordable Care Act was associated with a decrease in age-, race/ethnicity-, and sex-adjusted colorectal cancer incidence and colorectal cancer‒related mortality, implying that policies that remove barriers to screening, particularly financial burden from cost sharing, can result in improved colorectal cancer outcomes.

The Adolescent and Young Adult (AYA) Horizon Study: An AYA Cancer Survivorship Cohort.

BACKGROUND: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States. METHODS: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data. RESULTS: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall (N = 1,679), and notably lower among minority groups compared with non-Hispanic white women. CONCLUSIONS: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements. IMPACT: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.

Material and psychological financial hardship related to employment disruption among female adolescent and young adult cancer survivors.

BACKGROUND: The importance of addressing adverse financial effects of cancer among adolescents and young adults (AYAs) is paramount as survival improves. In the current study, the authors examined whether cancer-related employment disruption was associated with financial hardship among female AYA cancer survivors in North Carolina and California. METHODS: AYA cancer survivors identified through the North Carolina Central Cancer Registry and the Kaiser Permanente Northern/Southern California tumor registries responded to an online survey. Disrupted employment was defined as reducing hours, taking temporary leave, or stopping work completely because of cancer. Financial hardship was defined as material conditions or psychological distress related to cancer. Descriptive statistics and chi-square tests were used to characterize the invited sample and survey respondents. Marginal structural binomial regression models were used to estimate prevalence differences (PDs) and 95% confidence intervals (95% CIs). RESULTS: Among 1328 women employed at the time of their diagnosis, women were a median age of 34 years at the time of diagnosis and 7 years from diagnosis at the time of the survey and approximately 32% experienced employment disruption. A substantial percentage reported financial hardship related to material conditions (27%) or psychological distress (50%). In adjusted analyses, women with disrupted employment had a 17% higher burden of material conditions (95% CI, 10%-23%) and an 8% higher burden of psychological distress (95% CI, 1%-16%) compared with those without disruption. CONCLUSIONS: Financial hardship related to employment disruption among female AYA cancer survivors can be substantial. Interventions to promote job maintenance and transition back to the workforce after treatment, as well as improved workplace accommodations and benefits, present an opportunity to improve cancer survivorship.

Early life household intactness and timing of pubertal onset in girls: a prospective cohort study.

BACKGROUND: Girls who experience early-life familial stress may have heightened risk of early puberty, which has adverse implications for adolescent and adult health. We assessed the association between household intactness and pubertal onset using a racially/ethnically diverse cohort of girls from Northern California. METHODS: A prospective cohort study of 26,044 girls born in 2003-10. Girls living with both parents from birth up to 6 years were considered to come from "intact" households while others constituted "non-intact" households. Pubertal development was measured using pediatrician-assessed Tanner staging for breast and pubic hair. Pubertal onset was defined as the transition from Tanner Stage 1 to 2+ for breast (thelarche) and pubic hair (pubarche). Menarche data was collected from routine well-child questionnaires. Weibull regression models accommodating left, right, and interval censoring were used to determine risk of earlier thelarche and pubarche, and logistic regressions were used to assess the risk of early menarche (age < 12). RESULTS: Girls exposed to non-intact households before age 2 years were at increased risk for earlier thelarche and pubarche with significant effect modification by race/ethnicity, compared with girls from intact households. The associations were strongest among Black girls (adjusted hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 1.29,1.98; HR: 1.42, 95%CI: 1.15,1.77 for thelarche and pubarche, respectively). There were no significant associations among Asian/Pacific Islanders. Girls who lived in non-intact households before age 2 years were also at increased risk for earlier menarche, but without race/ethnic interaction. Adjustment for prepubertal obesity did not change these associations. Associations between living in non-intact households after age 2 years and early puberty were weaker but still significant. CONCLUSIONS: Exposure to a non-intact household early in life may increase the risk of early puberty in girls. Future psychosocial interventions focused on improving family cohesiveness and efforts to reduce childhood stress among families that are non-intact may mitigate these negative associations, thereby preventing future adverse health effects of early puberty and health disparities.

Impact of the Affordable Care Act on Colorectal Cancer Outcomes: A Systematic Review.

CONTEXT: The Patient Protection and Affordable Care Act increases healthcare access and includes provisions that directly impact access to and cost of evidence-based colorectal cancer screening. The Affordable Care Act's removal of cost sharing for colorectal cancer screening as well as Medicaid expansion have been hypothesized to increase screening and improve other health outcomes. However, since its passage in 2010, there is little consensus on the Affordable Care Act's impact. EVIDENCE ACQUISITION: Data from March 2010 to June 2019 were reviewed and 21 relevant studies were identified; 19 studies examined colorectal cancer screening with most finding increased screening rates. EVIDENCE SYNTHESIS: Eleven studies found significant increases, 5 found nonsignificant increases, 3 found nonsignificant decreases, and 1 study found a significant decrease in colorectal cancer screening. Three studies examined the impact on colorectal cancer incidence and stage of diagnosis, where a significant 2.4% increase in early diagnosis was found in one and a nonsignificant increase in incidence in another. However, survival improved after Medicaid expansion. CONCLUSIONS: Free preventive colorectal cancer screening and Medicaid expansion because of passage of the Affordable Care Act have been, in general, positively associated with modest improvements in screening rates across the country. Future studies are needed that investigate the longer-term impact of the Affordable Care Act on colorectal cancer morbidity and mortality rates, as screening is only the first step in treatment of cancerous and precancerous lesions, preventing them from progressing. Moreover, more studies examining subpopulations are needed to better assess where gaps in care remain.

Environmental Tobacco Smoke Exposure in Relation to Family Characteristics, Stressors and Chemical Co-Exposures in California Girls.

Childhood environmental tobacco smoke (ETS) exposure is a risk factor for adverse health outcomes and may disproportionately burden lower socioeconomic status groups, exacerbating health disparities. We explored associations of demographic factors, stressful life events, and chemical co-exposures, with cotinine levels, among girls in the CYGNET Study. Data were collected from families of girls aged 6-8 years old in Northern California, through clinic exams, questionnaires and biospecimens (n = 421). Linear regression and factor analysis were conducted to explore predictors of urinary cotinine and co-exposure body burdens, respectively. In unadjusted models, geometric mean cotinine concentrations were higher among Black (0.59 ug/g creatinine) than non-Hispanic white (0.27), Asian (0.32), or Hispanic (0.34) participants. Following adjustment, living in a rented home, lower primary caregiver education, and lack of two biologic parents in the home were associated with higher cotinine concentrations. Girls who experienced parental separation or unemployment in the family had higher unadjusted cotinine concentrations. Higher cotinine was also associated with higher polybrominated diphenyl ether and metals concentrations. Our findings have environmental justice implications as Black and socio-economically disadvantaged young girls experienced higher ETS exposure, also associated with higher exposure to other chemicals. Efforts to reduce ETS and co-exposures should account for other disparity-related factors.

Comparing Reported Dietary Supplement Intakes between Two 24-Hour Recall Methods: The Automated Self-Administered 24-Hour Dietary Assessment Tool and the Interview-Administered Automated Multiple Pass Method.

BACKGROUND: The Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24) includes a highly standardized multipass web-based recall that, like the Automated Multiple Pass Method (AMPM), captures detailed information about dietary intake using multiple probes and reminders to enhance recall of intakes. The primary distinction between ASA24 and AMPM is that the ASA24 user interface guides participants, thus removing the need for interviewers. OBJECTIVE: The objective of this study was to compare dietary supplement use reported on self-administered (ASA24-2011) vs interviewer-administered (AMPM) 24-hour recalls. DESIGN: The Food Reporting Comparison Study was an evaluation study designed to compare self-reported intakes captured using the self-administered ASA24 vs data collected via interviewer-administered AMPM recalls. Between 2010 and 2011, 1081 women and men were enrolled from three integrated health care systems that belong to the National Cancer Institute-funded Cancer Research Network: Security Health Plan Marshfield Clinic, Wisconsin; Henry Ford Health System, Michigan; and Kaiser Permanente Northern California, California. Quota sampling was used to ensure a balance of age, sex, and race/ethnicity. Participants were randomly assigned to four groups, and each group was asked to complete two dietary recalls: group 1, two ASA24s; group 2, two AMPMs; group 3, ASA24 first and AMPM second; and group 4, AMPM first and ASA24 second. Dietary supplements were coded using the 2007-2008 National Health and Nutrition Examination Survey Dietary Supplement Database. Analyses used the two one-sided tests, known as TOST, to assess equivalence of reported supplement use between methods. RESULTS: Complete 24-hour dietary recalls that included both dietary and supplement intake data were available for 1076 participants (507 men and 569 women). The proportions reporting supplement use via ASA24 and AMPM were 46% and 43%, respectively. These proportions were equivalent, with a small effect size of less than 20%. There were two exceptions in subgroup analyses: reported use among those 40 to 59 years of age and reported use by non-Hispanic black subjects were higher for ASA24 than AMPM. CONCLUSIONS: This study provides evidence that there is little difference in reported supplement use by mode of administration (ie, interview-administered vs self-administered recall).

Girls' Sleep Trajectories Across the Pubertal Transition: Emerging Racial/Ethnic Differences.

PURPOSE: This study aims to examine the longitudinal association between puberty and sleep in a diverse sample of girls and explore racial/ethnic differences in this association. METHODS: Using latent growth curve modeling, the present study measured pubertal development (timing and rate) and sleep (wake time and bedtime) in 1,239 socioeconomically and ethnically diverse girls starting when they were 6-8 years old and followed longitudinally for up to 8 years. Pubertal assessment was conducted annually in clinic by physical examination, classified by sexual maturation stage for breast and pubic hair development by trained raters. RESULTS: In line with previous research, black girls had the earliest pubertal development, followed by Hispanic, white, and Asian girls. Black girls, on average, reported significantly shorter sleep duration than Hispanic (ß = -.20, p < .001), Asian (ß = -.29, p = .002), and white (ß = -.35, p < .001) girls. In a series of dual-process models, we found that early pubertal timing predicted shorter sleep duration for early-maturing black girls (breast development: ß = .13, p = .005; pubic hair development: ß = .14, p = .012). There was no evidence of any association between pubertal rate and sleep. All models controlled for family socioeconomic status and body mass index. CONCLUSION: Sleep is essential for many aspects of youth development, including emotional, cognitive, and physical functioning. Developmental changes associated with puberty may put some early maturing girls at risk of shorter sleep duration in adolescence and exacerbate racial/ethnic disparities in health and well-being.

Childhood Socioeconomic Position and Pubertal Onset in a Cohort of Multiethnic Girls: Implications for Breast Cancer.

Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear.Methods: We studied the relationship of SEP to pubertal onset in a multiethnic cohort of 1,237 girls ages 6 to 8 years at baseline. Girls in three U.S. cities were followed for 5 to 8 years with annual clinical examinations from 2004 to 2012. SEP measures were examined for associations with pubertal onset, assessed by breast budding (thelarche) and pubic hair development (adrenarche). Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right, and interval censoring.Results: Higher body mass index percentage at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset. An SEP index comprising household family income, mother's education, and home ownership was an independent predictor of thelarche in adjusted models for all girls together and for white and Latina, separately, but not black girls, and the relationship varied by study site. The SEP index was not related to adrenarche in adjusted models. Overall, girls from the lowest quintile of SEP entered puberty on average 6% earlier than girls from the highest quintile (time ratio = 0.94; 95% confidence interval 0.91-0.97) in adjusted models.Conclusions: Our results suggest that early-life SEP may influence the timing of pubertal development.Impact: Factors related to lower SEP in childhood can adversely affect early development in ways that may increase the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1714-21. ©2017 AACR.

Primary care visit use after positive fecal immunochemical test for colorectal cancer screening.

BACKGROUND: For some patients, positive cancer screening test results can be a stressful experience that can affect future screening compliance and increase the use of health care services unrelated to medically indicated follow-up. METHODS: Among 483,216 individuals aged 50 to 75 years who completed a fecal immunochemical test to screen for colorectal cancer at a large integrated health care setting between 2007 and 2011, the authors evaluated whether a positive test was associated with a net change in outpatient primary care visit use within the year after screening. Multivariable regression models were used to evaluate the relationship between test result group and net changes in primary care visits after fecal immunochemical testing. RESULTS: In the year after the fecal immunochemical test, use increased by 0.60 clinic visits for patients with true-positive results. The absolute change in visits was largest (3.00) among individuals with positive test results who were diagnosed with colorectal cancer, but significant small increases also were found for patients treated with polypectomy and who had no neoplasia (0.36) and those with a normal examination and no polypectomy performed (0.17). Groups of patients who demonstrated an increase in net visit use compared with the true-negative group included patients with true-positive results (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.54-1.66), and positive groups with a colorectal cancer diagnosis (OR, 7.19; 95% CI, 6.12-8.44), polypectomy/no neoplasia (OR, 1.37; 95% CI, 1.27-1.48), and normal examination/no polypectomy (OR, 1.24; 95% CI, 1.18-1.30). CONCLUSIONS: Given the large size of outreach programs, these small changes can cumulatively generate thousands of excess visits and have a substantial impact on total health care use. Therefore, these changes should be included in colorectal cancer screening cost models and their causes investigated further. Cancer 2017;123:3744-3753. © 2017 American Cancer Society.

Impact of Social and Built Environment Factors on Body Size among Breast Cancer Survivors: The Pathways Study.

Background: As social and built environment factors have been shown to be associated with physical activity, dietary patterns, and obesity in the general population, they likely also influence these health behaviors among cancer survivors and thereby impact survivorship outcomes.Methods: Enhancing the rich, individual-level survey and medical record data from 4,505 breast cancer survivors in the Pathways Study, a prospective cohort drawn from Kaiser Permanente Northern California, we geocoded baseline residential addresses and appended social and built environment data. With multinomial logistic models, we examined associations between neighborhood characteristics and body mass index and whether neighborhood factors explained racial/ethnic/nativity disparities in overweight/obesity.Results: Low neighborhood socioeconomic status, high minority composition, high traffic density, high prevalence of commuting by car, and a higher number of fast food restaurants were independently associated with higher odds of overweight or obesity. The higher odds of overweight among African Americans, U.S.-born Asian Americans/Pacific Islanders, and foreign-born Hispanics and the higher odds of obesity among African Americans and U.S.-born Hispanics, compared with non-Hispanic whites, remained significant, although somewhat attenuated, when accounting for social and built environment features.Conclusions: Addressing aspects of neighborhood environments may help breast cancer survivors maintain a healthy body weight.Impact: Further research in this area, such as incorporating data on individuals' perceptions and use of their neighborhood environments, is needed to ultimately inform multilevel interventions that would ameliorate such disparities and improve outcomes for breast cancer survivors, regardless of their social status (e.g., race/ethnicity, socioeconomic status, nativity). Cancer Epidemiol Biomarkers Prev; 26(4); 505-15. ©2017 AACRSee all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population Sciences."

Training in the Conduct of Population-Based Multi-Site and Multi-Disciplinary Studies: the Cancer Research Network's Scholars Program.

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.

Neighborhood deprivation, race/ethnicity, and urinary metal concentrations among young girls in California.

BACKGROUND: Although metals can adversely impact children's health, the distribution of exposures to many metals, particularly among vulnerable subpopulations, is not well characterized. OBJECTIVES: We sought to determine whether neighborhood deprivation was associated with urinary concentrations of thirteen metals and whether observed relationships varied by race/ethnicity. METHODS: We obtained neighborhood characteristics from the 2005-2009 American Community Survey. Demographic information and urine samples from 400 healthy young girls in Northern California were obtained during a clinical visit. Urine samples were analyzed for metals using inductively-coupled plasma-mass spectrometry and levels were corrected for creatinine. We ran analysis of variance and generalized linear regression models to estimate associations of urinary metal concentrations with neighborhood deprivation and race/ethnicity and stratified multivariable models to evaluate possible interactions among predictors on metals concentrations. RESULTS: Urinary concentrations of three metals (barium, lead, antimony) varied significantly across neighborhood deprivation quartiles, and four (barium, lead, antimony, tin) varied across race/ethnicity groups. In models adjusted for family income and cotinine, both race/ethnicity (F3,224=4.34, p=0.01) and neighborhood deprivation (F3,224=4.32, p=0.01) were associated with antimony concentrations, but neither were associated with lead, barium, or tin, concentrations. Examining neighborhood deprivation within race/ethnicity groups, barium levels (pinteraction<0.01) decreased with neighborhood deprivation among Hispanic girls (ptrend<0.001) and lead levels (pinteraction=0.06) increased with neighborhood deprivation among Asian girls (ptrend=0.04). CONCLUSIONS: Our results indicate that children's vulnerability to some metals varies by neighborhood deprivation quartile and race/ethnicity. These differential distributions of exposures may contribute to environmental health disparities later in life.

Impact of Chemotherapy Dosing on Ovarian Cancer Survival According to Body Mass Index.

IMPORTANCE: Optimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose. OBJECTIVE: To evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival. DESIGN, SETTING, AND PARTICIPANTS: Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent. MAIN OUTCOMES AND MEASURES: Overall and ovarian cancer-specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis. RESULTS: The strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P < .001 for each agent). They also received lower relative dose intensity (RDI) for each agent and the combined regimen, calculated as average RDI (ARDI). Mean ARDI was 73.7% for obese class III women and 88.2% for normal-weight women (P < .001). Lower ARDI (<70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10-2.37]) and ovarian cancer-specific survival (HR, 1.69 [95% CI, 1.12-2.55]). Women who were obese at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with women with normal weight and no dose reduction, normal-weight women with dose reduction (ARDI < 85%) experienced worse survival (HR, 1.50 [95% CI, 1.02-2.21]). For each BMI category, those with ARDI less than 85% had worse survival than those without dose reduction. The improved survival among obese women was no longer apparent with dose reduction. CONCLUSIONS AND RELEVANCE: Lower RDI was an independent predictor of ovarian cancer mortality. This finding was strongest among normal-weight women but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in women with ovarian cancer.

Breastfeeding versus formula-feeding and girls' pubertal development.

To examine the association of breastfeeding or its duration with timing of girls' pubertal onset, and the role of BMI as a mediator in these associations. A population of 1,237 socio-economically and ethnically diverse girls, ages 6-8 years, was recruited across three geographic locations (New York City, Cincinnati, and the San Francisco Bay Area) in a prospective study of predictors of pubertal maturation. Breastfeeding practices were assessed using self-administered questionnaire/interview with the primary caregiver. Girls were seen on at least annual basis to assess breast and pubic hair development. The association of breastfeeding with pubertal timing was estimated using parametric survival analysis while adjusting for body mass index, ethnicity, birth-weight, mother's education, mother's menarcheal age, and family income. Compared to formula fed girls, those who were mixed-fed or predominantly breastfed showed later onset of breast development [hazard ratios 0.90 (95 % CI 0.75, 1.09) and 0.74 (95 % CI 0.59, 0.94), respectively]. Duration of breastfeeding was also directly associated with age at onset of breast development (p trend = 0.008). Associations between breastfeeding and pubic hair onset were not significant. In stratified analysis, the association of breastfeeding and later breast onset was seen in Cincinnati girls only. The association between breast feeding and pubertal onset varied by study site. More research is needed about the environments within which breastfeeding takes place in order to better understand whether infant feeding practices are a potentially modifiable risk factor that may influence age at onset of breast development and subsequent risk for disease in adulthood.