Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer.

PURPOSE: Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. METHODS: In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015). RESULTS: In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status. CONCLUSION: We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.

Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study.

SCOPE: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. METHODS AND RESULTS: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure. CONCLUSION: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.

Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study.

BACKGROUND: Women with breast cancer are at higher risk of cardiovascular disease (CVD) compared with women without breast cancer. Whether higher diet quality at breast cancer diagnosis lowers this risk remains unknown. We set out to determine if higher diet quality at breast cancer diagnosis was related to lower risk of CVD and CVD-related death. METHODS: This analysis included 3415 participants from the Pathway Study, a prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through December 31, 2021. Scores from 5 diet quality indices consistent with healthy eating were obtained at the time of breast cancer diagnosis. Scores were categorized into ascending quartiles of concordance for each diet quality index, and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. P values were 2-sided. RESULTS: The Dietary Approaches to Stop Hypertension diet quality index was associated with lower risk of heart failure (HR = 0.53, 95% CI = 0.33 to 0.87; Ptrend = .03), arrhythmia (HR = 0.77, 95% CI = 0.62 to 0.94; Ptrend = .008), cardiac arrest (HR = 0.77, 95% CI = 0.61 to 0.96; Ptrend = .02), valvular heart disease (HR = 0.79, 95% CI = 0.64 to 0.98; Ptrend = .046), venous thromboembolic disease (HR = 0.75, 95% CI = 0.60 to 0.93; Ptrend = .01), and CVD-related death (HR = 0.70, 95% CI = 0.50 to 0.99; Ptrend = .04), when comparing the highest with lowest quartiles. Inverse associations were also found between the healthy plant-based dietary index and heart failure (HR = 0.60, 95% CI = 0.39 to 0.94; Ptrend = .02), as well as the alternate Mediterranean dietary index and arrhythmia (HR = 0.74, 95% CI = 0.60 to 0.93; Ptrend = .02). CONCLUSION: Among newly diagnosed breast cancer patients, higher diet quality at diagnosis was associated with lower risk of CVD events and death.

Perspective: Beyond the Mediterranean Diet -- Exploring Latin American, Asian, and African Heritage Diets as Cultural Models of Healthy Eating.

The Mediterranean diet is a well-studied cultural model of healthy eating, yet research on healthy models from other cultures and cuisines has been limited. This perspective article summarizes the components of traditional Latin American, Asian, and African Heritage diets, their association with diet quality and markers of health, and implications for nutrition programs and policy. Though these diets differ in specific foods and flavors, we present a common thread that emphasizes healthful plant foods, and that is consistent with high dietary quality and low rates of major causes of disability and deaths. In this perspective, we propose that nutrition interventions that incorporate these cultural models of healthy eating show promise, though further research is needed to determine health outcomes and best practices for implementation.

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer.

Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.

Differences in Smoking Behavior by Nativity, Race/Ethnicity, and Education Among Women Diagnosed with Breast Cancer.

BACKGROUND: We evaluated smoking differences across nativity and race/ethnicity among women diagnosed with breast cancer. METHODS: In our Northern Californian pooled population of 5,653 [670 Asian, 690 Hispanic, and 4,300 Non-Hispanic White (White)] women diagnosed with breast cancer, we evaluated smoking differences across nativity, race/ethnicity, and acculturation and effect modification of nativity by race/ethnicity and education. RESULTS: Foreign-born women currently smoked less than US-born women [odds ratio (OR) = 0.46, 95% confidence limit (CL): 0.29, 0.72]. Hispanic (OR = 0.50, 95% CL: 0.32, 0.78) women currently smoked less than White women. Among those who ever smoked (n = 2,557), foreign-born women smoked 5.23 fewer pack-years (PY) than US-born women (95% CL: -2.75, -7.70). Furthermore, Asian (-4.60, 95% CL: -0.81, -8.39) and Hispanic (-6.79, 95% CL: -4.14, -9.43) women smoked fewer PY than White women. Associations were generally suggestive of greater smoking with greater acculturation (immigration age, US years, survey language). Finally, associations for nativity differed by education but not race/ethnicity, with a higher likelihood of smoking in US-born women only among those with less than a bachelor's degree (OR = 2.84, 95% CL: 2.15, 3.77) (current smoking: p = 0.01, PY: p = 0.05). CONCLUSIONS: Asian and Hispanic (vs. White) and foreign-born (vs. US-born) breast cancer survivors reported fewer smoking behaviors. Smoking differences across nativity and education were driven by higher rates of smoking in US-born women with lower educational attainment. IMPACT: Smoking behavioral patterns were similar among breast cancer survivors and the general population, informing potential smoking interventions.

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

Background: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine- induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. Methods: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population- level SARS-CoV-2 seroprevalence. EHR and survey data were incorporated to determine spike antibody positivity due to SARS-CoV-2 infection and COVID-19 vaccination. We used sampling and non-response weighting to create population-level estimates. Results: We enrolled 4,319 persons over six recruitment waves. SARS-CoV-2 spike antibody seroprevalence increased from 83.3% (CI 77.0-88.9) in May 2021 to 93.5% (CI 89.5-97.5) in April 2022. By April 2022, 68.5% (CI 61.9-74.3) of the population was seropositive from COVID-19 vaccination only, 13.9% (10.7-17.9) from COVID-19 vaccination and prior diagnosed SARS-CoV-2 infection, 8.2% (CI 4.5- 14.5) from prior diagnosed SARS-CoV-2 infection only and 2.9% (CI 1.1-7.6) from prior undiagnosed SARS-CoV-2 infection only. We found high agreement (≥97%) between EHR and survey data for ascertaining COVID-19 vaccination and SARS-CoV-2 infection status. Conclusions: By April 2022, 93.5% of persons had detectable SARS-CoV-2 spike antibody, predominantly from COVID-19 vaccination. In this highly vaccinated population and over 18 months into the pandemic, SARS-CoV-2 infection without COVID-19 vaccination was a small contributor to overall population-level seroprevalence. Article summary: By April 2022, >93% of people had antibodies to SARS-CoV-2 with COVID-19 vaccination as the main driver of overall population-level seroprevalence in our healthcare system. SARS-CoV-2 infection without vaccination made a small contribution to population-level seroprevalence in our healthcare system.

Use of Cancer-Directed therapy at the end of life among adolescents and young adults.

BACKGROUND: Adolescents and young adults (AYAs) frequently receive chemotherapy near death. We know less about use of targeted agents and immunotherapy or trends over time. METHODS: We conducted a retrospective cohort study of 1,836 AYAs with cancer who died between 2009-2019 after receiving care at one of three sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs. RESULTS: Over the study period, 35% of AYAs received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Fifty-six percent received at least one form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of AYAs receiving targeted therapy (odds ratio (OR) 1.05 per year of death, 95% confidence interval (CI) 1.02-1.10, P = .006), immunotherapy (OR 1.27, 95%CI 1.18-1.38, P<.0001), and any cancer-directed therapy (OR1.04, 95%CI 1.01-1.08, P=.01) in the last 90 days of life increased over time. CONCLUSIONS: More than half of AYAs receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy are increasing over time. While some AYAs may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of AYAs approaching death.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors.

Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.

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.

Evaluation of Algorithms Using Automated Health Plan Data to Identify Breast Cancer Recurrences.

BACKGROUND: We updated algorithms to identify breast cancer recurrences from administrative data, extending previously developed methods. METHODS: In this validation study, we evaluated pairs of breast cancer recurrence algorithms (vs. individual algorithms) to identify recurrences. We generated algorithm combinations that categorized discordant algorithm results as no recurrence [High Specificity and PPV (positive predictive value) Combination] or recurrence (High Sensitivity Combination). We compared individual and combined algorithm results to manually abstracted recurrence outcomes from a sample of 600 people with incident stage I-IIIA breast cancer diagnosed between 2004 and 2015. We used Cox regression to evaluate risk factors associated with age- and stage-adjusted recurrence rates using different recurrence definitions, weighted by inverse sampling probabilities. RESULTS: Among 600 people, we identified 117 recurrences using the High Specificity and PPV Combination, 505 using the High Sensitivity Combination, and 118 using manual abstraction. The High Specificity and PPV Combination had good specificity [98%, 95% confidence interval (CI): 97-99] and PPV (72%, 95% CI: 63-80) but modest sensitivity (64%, 95% CI: 44-80). The High Sensitivity Combination had good sensitivity (80%, 95% CI: 49-94) and specificity (83%, 95% CI: 80-86) but low PPV (29%, 95% CI: 25-34). Recurrence rates using combined algorithms were similar in magnitude for most risk factors. CONCLUSIONS: By combining algorithms, we identified breast cancer recurrences with greater PPV than individual algorithms, without additional review of discordant records. IMPACT: Researchers should consider tradeoffs between accuracy and manual chart abstraction resources when using previously developed algorithms. We provided guidance for future studies that use breast cancer recurrence algorithms with or without supplemental manual chart abstraction.

Risk of adverse birth outcomes after adolescent and young adult cancer.

BACKGROUND: Many women diagnosed with cancer as adolescents and young adults (AYAs, age 15-39 years) want biological children after cancer but lack information on the potential impact of their cancer history on future reproductive outcomes. We investigated the risk of adverse birth outcomes among AYA cancer survivors. METHODS: We identified insured women diagnosed with AYA breast cancer, thyroid cancer, gynecologic cancers, lymphoma, or melanoma from 2003 to 2016 in the state of North Carolina or the Kaiser Permanente health care systems in northern and southern California. Post-diagnosis births to cancer survivors were each matched with up to 5 births to women without cancer. Risk ratios for preterm birth (<37 completed weeks), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and small for gestational age (SGA, <10th percentile of weight for gestational age) were estimated using modified Poisson regression. RESULTS: Analyses included 1648 births to 1268 AYA cancer survivors and 7879 births to 6066 women without cancer. Overall, risk of preterm birth, very preterm birth, low birth weight, and SGA did not significantly differ between births to women with and without cancer. However, births to women with gynecologic cancers had a significantly increased risk of low birth weight (risk ratio = 1.82; 95% confidence interval: 1.03 to 3.21) and suggested increased risk of preterm birth (risk ratio = 1.59; 95% confidence interval: 0.99 to 2.54). Chemotherapy exposure was not associated with increased risk of adverse birth outcomes. CONCLUSIONS: Women with gynecologic cancers, but not other cancers, had an increased risk of adverse birth outcomes compared to women without cancer.

Environmental and Occupational Exposures and Prognosis in Patients with Non-Muscle Invasive Bladder Cancer in the Be-Well Study.

Bladder cancer is primarily diagnosed as non-muscle invasive bladder cancer (NMIBC) with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1,472 patient with newly diagnosed NMIBC from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (HR = 1.79; 95% CI: 1.04, 3.09), specifically increased progression into muscle-invasive disease (HR = 2.28; 95% CI: 1.16, 4.50). Exposure to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: OR = 1.43; 95% CI: 1.11, 1.84; arsenic, OR = 1.27; 95% CI: 1.01, 1.63), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI: 1.12, 1.69). Our findings suggest that history of these exposures may benefit current risk stratification systems to tailor clinical care and improve prognosis in patients with NMIBC.

What Constitutes Quality of Life? Perspectives of Adolescents and Young Adults With Advanced Cancer.

BACKGROUND: Adolescents and young adults (AYAs) with advanced cancer identify maintaining a good quality of life (QoL) as a central goal of end-of-life care. QoL is a dynamic and subjective overarching concept that refers to an individual's relative satisfaction with their own life. Despite its importance to AYAs with advanced cancer, a patient-centered definition of QoL is lacking in this population. PATIENTS AND METHODS: This qualitative secondary analysis of semistructured interviews was conducted across 3 institutions and 1 online support community among AYA patients with advanced cancer, family caregivers, and health care providers who cared for living or recently deceased AYAs. Interviewees were asked about priorities in receipt of care. Interviews were transcribed using NVivo software for primary analysis, and previously coded excerpts were screened for references to QoL. Relevant excerpts were sorted into organizing domains. RESULTS: Participants included 23 AYA patients, 28 family caregivers, and 29 health care providers (including physicians, nurses, nurse practitioners, social workers, and psychologists). Four domains of QoL were identified: psychosocial and physical well-being, dignity, normalcy, and personal and family relationships. Within each domain there was agreement across AYAs, caregivers, and health care providers, with nuanced perspectives provided by AYAs of different ages. Personal and family relationships was the most frequently referenced domain of QoL among all participants. A common feature of each domain was that adaptation to current circumstances impacted perspectives on QoL. Patients valued active participation in the development of a care plan that supported these domains. CONCLUSIONS: AYAs with advanced cancer, their caregivers, and health care providers agree on several broad domains of QoL in this population. To provide high-quality, patient-centered care, care plans should integrate these domains to enable AYAs to maximize their QoL throughout their advanced cancer care.

Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults.

There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.

Hypothetical Interventions on Diet Quality and Lifestyle Factors to Improve Breast Cancer Survival: The Pathways Study.

BACKGROUND: The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited. METHODS: This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated. RESULTS: Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced. CONCLUSIONS: Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors. IMPACT: We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors.

Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche. METHODS: In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6-8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging. PFAS concentrations were measured in the first serum sample of 704 girls. In 304 GC girls, estradiol (E2), estrone (E1), testosterone (T), and dihydroepiandrosterone sulfate (DHEAS) were measured in serum at four time points around puberty. Relationships between PFAS and age at thelarche, pubarche, and menarche were analyzed using survival and structural equation models. The association between PFAS and reproductive hormones was assessed using linear regression models. RESULTS: Median PFOA serum concentrations in GC (N=353, 7.3 ng/mL) and the SFBA (N=351, 5.8 ng/mL) were higher than in the U.S. POPULATION: In multivariable Cox proportional hazard models [adjusted for race, body mass index (BMI)], increasing serum log-transformed PFOA was associated with a delay in pubarche [hazard ratio (HR)=0.83; 95% CI: 0.70, 0.99] and menarche (HR=0.04; 95% CI: 0.01, 0.25). Structural equation models indicated a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone. Increased PFOA had a statistically significant direct effect of delay on all three milestones, as did BMI. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) also were associated with later thelarche, and Me-PFOSA-AcOH also with later pubarche. PFOA was inversely associated with DHEAS (p<0.01), E1 (p=0.04), and T (p=0.03) concentrations at 6 months prior to puberty. CONCLUSIONS: PFAS may delay pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEAS and E1 associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty. https://doi.org/10.1289/EHP11811.

Incidence and Survival for Patients Diagnosed With Breast, Colorectal, and Lung Cancer in an Integrated System.

INTRODUCTION: Documenting trends in cancer incidence and survival is a national priority. This study estimated age- and sex-adjusted incidence and 5-year relative survival among patients with cancer diagnosed within Kaiser Permanente compared to Surveillance, Epidemiology, and End Results (SEER) estimates. METHODS: The cohort included Kaiser Permanente health plan members diagnosed with breast (BC), colorectal (CRC), or lung cancer (LC) between January 1, 1999 and December 31, 2018. Incidence was computed as age-adjusted rates per 100,000 member-years. SEER*Stat was used to compute 5-year relative survival. RESULTS: Kaiser Permanente BC incidence rates were persistently higher than SEER from 2004 (126.5 [95% confidence interval (CI) = 123.2-129.9] vs 122.6 [95% CI = 121.3-123.2]) through 2013 (132.06 [95% CI = 129.5-135.7] vs 126.7 [95% CI = 125.9-127.5]). Kaiser Permanente CRC and LC incidence rates were lower than SEER for all years except 2008, showing a spike in CRC incidence (51.5 [95% CI = 49.9-53.0] vs 46.1 [95% CI = 45.7-46.4]). Kaiser Permanente BC, CRC, and LC survival estimates for all stages were higher than SEER. CONCLUSIONS: Incidence rates for all-stage and localized-stage BC were consistently higher for Kaiser Permanente than for SEER. CRC and LC rates were lower. Kaiser Permanente survival rates were consistently higher than for SEER. The strengths of these findings are associated with the ability to capture "gold-standard" cancer registry data on defined Kaiser Permanente populations. However, findings should be interpreted cautiously given differences in the underlying populations and secular and regional differences between Kaiser Permanente and SEER. The Kaiser Permanente population is younger and more racially diverse than SEER aggregate populations, and Kaiser Permanente members are insured with access to preventive care (eg, smoking cessation programs, cancer screening).

Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study.

BACKGROUND: The impact of alcohol consumption on breast cancer (BC) prognosis remains unclear. METHODS: The authors examined short-term alcohol intake in relation to recurrence and mortality in 3659 women who were diagnosed with stage I-IV BC from 2003 to 2013 in the Pathways Study. Alcohol drinking in the past 6 months was assessed at cohort entry (mean, 2 months postdiagnosis) and 6 months later using a food-frequency questionnaire. Study end points were recurrence and death from BC, cardiovascular disease, and all causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS: Over an average follow-up of 11.2 years, 524 recurrences and 834 deaths (369 BC-specific and 314 cardiovascular disease-specific) occurred. Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers. Overall, alcohol consumption was not associated with recurrence or mortality. However, women with higher body mass index (BMI ≥ 30 kg/m2 ) had lower risk of overall mortality with increasing alcohol consumption for occasional drinking (HR, 0.71; 95% CI, 0.54-0.94) and regular drinking (HR, 0.77; 95% CI, 0.56-1.08) around the time of diagnosis, along with 6 months later, in a dose-response manner (p < .05). Women with lower BMI (<30 kg/m2 ) were not at higher risk of mortality but were at possibly higher, yet nonsignificant, risk of recurrence for occasional drinking (HR, 1.29; 95% CI, 0.97-1.71) and regular drinking (HR, 1.19; 95% CI, 0.88-1.62). CONCLUSIONS: Alcohol drinking around the time of and up to 6 months after BC diagnosis was associated with lower risk of all-cause mortality in obese women. A possible higher risk of recurrence was observed in nonobese women.