Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients.

INTRODUCTION: Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. METHODS: We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. RESULTS: We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. CONCLUSIONS: Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Racial disparities in initiation of chemotherapy among breast cancer patients with discretionary treatment indication in the state of Georgia.

PURPOSE: The majority of breast cancer patients are diagnosed with early-stage estrogen receptor (ER) positive disease. Despite effective treatments for these cancers, Black women have higher mortality than White women. We investigated demographic and clinical factors associated with receipt of chemotherapy among those with a discretionary indication who are at risk for overtreatment. METHODS: Using Georgia Cancer Registry data, we identified females diagnosed with ER positive breast cancer who had a discretionary indication for chemotherapy (2010-2017). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associating patient demographic and clinical characteristics with chemotherapy initiation overall, and comparing non-Hispanic Black (NHB) with non-Hispanic White (NHW) women within strata of patient factors. RESULTS: We identified 11,993 ER positive breast cancer patients with a discretionary indication for chemotherapy. NHB patients were more likely to initiate chemotherapy compared with NHW women (OR = 1.41, 95% CI: 1.28, 1.56). Race differences in chemotherapy initiation were pronounced among those who did not receive Oncotype DX testing (OR = 1.47, 95% CI: 1.31, 1.65) and among those residing in high socioeconomic status neighborhoods (OR = 2.48, 95% CI: 1.70, 3.61). However, we observed equitable chemotherapy receipt among patients who received Oncotype DX testing (OR = 0.90, 95% CI: 0.71, 1.14), were diagnosed with grade 1 disease (OR = 1.00, 95% CI: 0.74, 1.37), and those resided in rural areas (OR = 1.01, 95% CI: 0.76, 1.36). CONCLUSION: We observed racial disparities in the initiation of chemotherapy overall and by sociodemographic and clinical factors, and more equitable outcomes when clinical guidelines were followed.

Association of inflammation-related exposures and ovarian cancer survival in a multi-site cohort study of Black women.

BACKGROUND: An association was observed between an inflammation-related risk score (IRRS) and worse overall survival (OS) among a cohort of mostly White women with invasive epithelial ovarian cancer (EOC). Herein, we evaluated the association between the IRRS and OS among Black women with EOC, a population with higher frequencies of pro-inflammatory exposures and worse survival. METHODS: The analysis included 592 Black women diagnosed with EOC from the African American Cancer Epidemiology Study (AACES). Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of the IRRS and OS, adjusting for relevant covariates. Additional inflammation-related exposures, including the energy-adjusted Dietary Inflammatory Index (E-DIITM), were evaluated. RESULTS: A dose-response trend was observed showing higher IRRS was associated with worse OS (per quartile HR: 1.11, 95% CI: 1.01-1.22). Adding the E-DII to the model attenuated the association of IRRS with OS, and increasing E-DII, indicating a more pro-inflammatory diet, was associated with shorter OS (per quartile HR: 1.12, 95% CI: 1.02-1.24). Scoring high on both indices was associated with shorter OS (HR: 1.54, 95% CI: 1.16-2.06). CONCLUSION: Higher levels of inflammation-related exposures were associated with decreased EOC OS among Black women.

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Purpose: Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue. Methods: We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017). Contemporary redlining was derived for census tracts using the Home Mortgage Disclosure Act database. Linear regression models were used to calculate the association between contemporary redlining and methylation in breast tumor tissue. We also examined epigenetic age acceleration for two different metrics, regressing ß values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. We employed multivariable Cox-proportional hazards models and 95% confidence intervals (CI) to estimate the association between aberrant methylation and mortality. Results: Contemporary redlining was associated with 5 CpG sites after adjustment for multiple comparisons (FDR<0.10). All genes were implicated in breast carcinogenesis, including genes related to inflammation, immune function and stress response (ANGPT1, PRG4 and PRG4). Further exploration of the top 25 CpG sites, identified interaction of 2 sites (MRPS28 and cg11092048) by ER status and 1 site (GDP1) was associated with all-cause mortality. Contemporary redlining was associated with epigenetic age acceleration by the Hannum metric (ß=5.35; CI 95%=0.30,10.4) and showed positive but non-significant correlation with the other clock. Conclusion: We identified novel associations between neighborhood contemporary redlining and the breast tumor DNA methylome, suggesting that racist policies leading to inequitable social and environmental exposures, may impact the breast tumor epigenome. Additional research on the potential implications for prognosis is needed.

Associations between health insurance status, neighborhood deprivation, and treatment delays in women with breast cancer living in Georgia.

BACKGROUND: Little is known regarding the association between insurance status and treatment delays in women with breast cancer and whether this association varies by neighborhood socioeconomic deprivation status. METHODS: In this cohort study, we used medical record data of women diagnosed with breast cancer between 2004 and 2022 at two Georgia-based healthcare systems. Treatment delay was defined as >90 days to surgery or >120 days to systemic treatment. Insurance coverage was categorized as private, Medicaid, Medicare, other public, or uninsured. Area deprivation index (ADI) was used as a proxy for neighborhood-level socioeconomic status. Associations between delayed treatment and insurance status were analyzed using logistic regression, with an interaction term assessing effect modification by ADI. RESULTS: Of the 14,195 women with breast cancer, 54% were non-Hispanic Black and 52% were privately insured. Compared with privately insured patients, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 79%, 75%, and 27% higher odds of delayed treatment, respectively (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.32-2.43; OR: 1.75, 95% CI: 1.43-2.13; OR: 1.27, 95% CI: 1.06-1.51). Among patients living in low-deprivation areas, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 100%, 84%, and 26% higher odds of delayed treatment than privately insured patients (OR: 2.00, 95% CI: 1.44-2.78; OR: 1.84, 95% CI: 1.48-2.30; OR: 1.26, 95% CI: 1.05-1.53). No differences in the odds of delayed treatment by insurance status were observed in patients living in high-deprivation areas. DISCUSSION/CONCLUSION: Insurance status was associated with treatment delays for women living in low-deprivation neighborhoods. However, for women living in neighborhoods with high deprivation, treatment delays were observed regardless of insurance status.

Sociodemographic disparities in targeted therapy in ovarian cancer in a national sample.

Background: The treatment landscape for ovarian cancer has changed in recent years with the introduction of targeted therapies to treat patients with advanced disease. We investigated patient demographic and clinical factors associated with use of targeted therapies as a part of the first-line treatment for ovarian cancer. Methods: This study included patients diagnosed with stage I-IV ovarian cancer between 2012 and 2019 from the National Cancer Database. Information on demographic and clinical characteristics were collected and described using frequency and percent across receipt of targeted therapy. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (CI) associating patient demographic and clinical factors with receipt of targeted therapy. Results: Among 99,286 ovarian cancer patients (mean age 62 years), 4.1% received targeted therapy. The rate of targeted therapy receipt across racial and ethnic groups over the study period was fairly similar; however, non-Hispanic Black women were less likely to receive targeted therapy than their non-Hispanic White counterparts (OR=0.87, 95% CI: 0.76-1.00). Patients who received neoadjuvant chemotherapy were more likely to receive targeted therapy than those who received adjuvant chemotherapy (OR=1.26; 95% CI: 1.15-1.38). Moreover, among patients who received targeted therapy, 28% received neoadjuvant targeted therapy, with non-Hispanic Black women being most likely to receive neoadjuvant targeted therapy (34%) compared with other racial and ethnic groups. Conclusions: We observed differences in receipt of targeted therapy by factors such as age at diagnosis, stage, and comorbidities present at diagnosis, as well as factors related to healthcare access-including neighborhood education level and health insurance status. Approximately 28% of patients received targeted therapy in the neoadjuvant setting, which could negatively impact treatment outcomes and survival due to the increased risk of complications associated with targeted therapies that may delay or prevent surgery. These results warrant further evaluation in a cohort of patients with more comprehensive treatment information.

Associations of Post-Diagnosis Lifestyle with Prognosis in Women with Invasive Breast Cancer.

BACKGROUND: Lifestyle habits can impact breast cancer development, but its impact on breast cancer prognosis remains unclear. We investigated associations of post-diagnosis lifestyle with mortality and recurrence in 1,964 women with invasive breast cancer enrolled in the Kaiser Permanente Northern California Pathways Study shortly after diagnosis with lifestyle information at baseline (2005-2013) and the 2-year follow-up. METHODS: We calculated a post-diagnosis lifestyle score (range, 0-18) based on 9 diet, physical activity, and body weight recommendations from the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) using follow-up data (body weight also included baseline data); higher scores indicate greater guideline concordance. Similarly, we calculated a pre-diagnosis lifestyle score using baseline data to investigate pre- to post-diagnosis changes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models, with follow-up through December 2018 (observing 290 deaths and 176 recurrences). RESULTS: The 2-year post-diagnosis lifestyle score was inversely associated with all-cause mortality (ACM; HR per 2-point increase = 0.90; 95% CI, 0.82-0.98), and breast cancer-related mortality (HR, 0.79; 95% CI, 0.67-0.95), but not recurrence. Relative to women who maintained low concordance with recommendations at both time points, women who maintained high concordance had a lower risk of ACM (HR, 0.61, 95% CI, 0.37-1.03). Improved concordance with some specific recommendations (particularly PA) may be associated with a lower hazard of ACM (HRPA, 0.52; 95% CI, 0.35-0.78). CONCLUSIONS: Results suggest that women with breast cancer may benefit from a post-diagnosis lifestyle aligned with ACS/ASCO guidelines. IMPACT: This information may potentially guide lifestyle recommendations for breast cancer survivors to reduce mortality risk.

Role of neighborhood context in ovarian cancer survival disparities: current research and future directions.

Ovarian cancer is the fifth leading cause of cancer-associated mortality among US women with survival disparities seen across race, ethnicity, and socioeconomic status, even after accounting for histology, stage, treatment, and other clinical factors. Neighborhood context can play an important role in ovarian cancer survival, and, to the extent to which minority racial and ethnic groups and populations of lower socioeconomic status are more likely to be segregated into neighborhoods with lower quality social, built, and physical environment, these contextual factors may be a critical component of ovarian cancer survival disparities. Understanding factors associated with ovarian cancer outcome disparities will allow clinicians to identify patients at risk for worse outcomes and point to measures, such as social support programs or transportation aid, that can help to ameliorate such disparities. However, research on the impact of neighborhood contextual factors in ovarian cancer survival and in disparities in ovarian cancer survival is limited. This commentary focuses on the following neighborhood contextual domains: structural and institutional context, social context, physical context represented by environmental exposures, built environment, rurality, and healthcare access. The research conducted to date is presented and clinical implications and recommendations for future interventions and studies to address disparities in ovarian cancer outcomes are proposed.

Neoadjuvant Chemotherapy in Ovarian Cancer: Are There Racial Disparities in Use and Survival?

BACKGROUND: We investigated racial and ethnic disparities in treatment sequence [i.e., neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) versus primary debulking surgery (PDS) plus adjuvant chemotherapy] among patients with ovarian cancer and its contribution to disparities in mortality. METHODS: Study included 37,566 women ages ≥18 years, diagnosed with stage III/IV ovarian cancer from the National Cancer Database (2004-2017). Logistic regression was used to compute ORs and 95% confidence intervals (CI) for racial and ethnic disparities in treatment sequence. Cox proportional hazards regression was used to estimate HRs and 95% CI for racial and ethnic disparities in all-cause mortality. RESULTS: Non-Hispanic Black (NHB) and Asian women were more likely to receive NACT plus IDS relative to PDS plus adjuvant chemotherapy than non-Hispanic White (NHW) women (OR: 1.12; 95% CI: 1.02-1.22 and OR: 1.12; 95% CI: 0.99-1.28, respectively). Compared with NHW women, NHB women had increased hazard of all-cause mortality (HR: 1.14; 95% CI: 1.09-1.20), whereas Asian and Hispanic women had a lower hazard of all-cause mortality (HR: 0.81; 95% CI: 0.74-0.88 and HR: 0.83; 95% CI: 0.77-0.88, respectively), which did not change after accounting for treatment sequence. CONCLUSIONS: NHB women were more likely to receive NACT plus IDS and experience a higher all-cause mortality rates than NHW women. IMPACT: Differences in treatment sequence did not explain racial disparities in all-cause mortality. Further evaluation of racial and ethnic differences in treatment and survival in a cohort of patients with detailed treatment information is warranted.

Association of Race and Area Deprivation With Breast Cancer Survival Among Black and White Women in the State of Georgia.

Importance: Increasing evidence suggests that low socioeconomic status and geographic residence in disadvantaged neighborhoods contribute to disparities in breast cancer outcomes. However, little epidemiological research has sought to better understand these disparities within the context of location. Objective: To examine the association between neighborhood deprivation and racial disparities in mortality among Black and White patients with breast cancer in the state of Georgia. Design, Setting, and Participants: This population-based cohort study collected demographic and geographic data from patients diagnosed with breast cancer between January 1, 2004, and February 11, 2020, in 3 large health care systems in Georgia. A total of 19 580 patients with breast cancer were included: 12 976 from Piedmont Healthcare, 2285 from Grady Health System, and 4319 from Emory Healthcare. Data were analyzed from October 2, 2020, to August 11, 2022. Exposures: Area deprivation index (ADI) scores were assigned to each patient based on their residential census block group. The ADI was categorized into quartile groups, and associations between ADI and race and ADI × race interaction were examined. Main Outcomes and Measures: Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% CIs associating ADI with overall mortality by race. Kaplan-Meier curves were used to visualize mortality stratified across racial and ADI groups. Results: Of the 19 580 patients included in the analysis (mean [SD] age at diagnosis, 58.8 [13.2] years), 3777 (19.3%) died during the course of the study. Area deprivation index contributed differently to breast cancer outcomes for Black and White women. In multivariable-adjusted models, living in a neighborhood with a greater ADI (more deprivation) was associated with increased mortality for White patients with breast cancer; compared with the ADI quartile of less than 25 (least deprived), increased mortality HRs were found in quartiles of 25 to 49 (1.22 [95% CI, 1.07-1.39]), 50 to 74 (1.32 [95% CI, 1.13-1.53]), and 75 or greater (1.33 [95% CI, 1.07-1.65]). However, an increase in the ADI quartile group was not associated with changes in mortality for Black patients with breast cancer (quartile 25 to 49: HR, 0.81 [95% CI, 0.61-1.07]; quartile 50 to 74: HR, 0.91 [95% CI, 0.70-1.18]; and quartile ≥75: HR, 1.05 [95% CI, 0.70-1.36]). In neighborhoods with an ADI of 75 or greater, no racial disparity was observed in mortality (HR, 1.11 [95% CI, 0.92-1.36]). Conclusions and Relevance: Black women with breast cancer had higher mortality than White women in Georgia, but this disparity was not explained by ADI: among Black patients, low ADI was not associated with lower mortality. This lack of association warrants further investigation to inform community-level approaches that may mitigate the existing disparities in breast cancer outcomes in Georgia.

Barriers to breast cancer screening in Atlanta, GA: results from the Pink Panel survey at faith-based institutions.

PURPOSE: Our research sought to describe barriers to mammography screening among a sample of predominantly Black women in metropolitan Atlanta, Georgia. METHODS: The Pink Panel project convened community leaders from faith-based institutions to administer an offline survey to women via convenience sampling at fourteen churches in Atlanta in late 2019 and early 2020. With the COVID-19 pandemic, the research team switched to an online survey. The survey included seven questions about breast cancer awareness, barriers to breast cancer screening, and screening status. We used residence information to attain the 9-digit zip code to link to the Area Deprivation Index at the Census Block Group neighborhood level. We report results as descriptive statistics of the barriers to mammography screening. RESULTS: The 643 women represented 21 counties in Georgia, predominantly from metropolitan Atlanta, and 86% identified as Black. Among women aged 40 and older, 90% have ever had a mammogram. Among all women, 79% have ever had a mammogram, and 86% indicated that they would get a mammogram if offered in their neighborhood. The top barriers to mammography screening were lack of health insurance and high cost. Barriers to mammography screening did not differ substantially by Area Deprivation Index. CONCLUSION: Among metropolitan Atlanta women aged 40+ , nearly all reported ever having a mammogram. However, addressing the barriers, including lack of health insurance and high cost, that women reported may further improve mammography screening rates.

Mortality Patterns of Synchronous Uterine and Ovarian Cancers: A SEER Registry Analysis.

BACKGROUND: The degree to which uterine cancer metastatic to the ovary is misdiagnosed as synchronous stage I uterine and ovarian cancers is unclear. We sought to determine whether patients with synchronous cancers had mortality patterns similar to either stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. METHODS: The Surveillance, Epidemiology, and End Results database was used to compare mortality of patients with synchronous stage I uterine and stage I ovarian cancers versus those with stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. We calculated age-adjusted mortality hazard ratios (HR) and 95% confidence intervals (CI) accounting for calendar year and grade, adjuvant treatment, grade 1 endometrioid cancers, grade 3 endometrioid cancers, and stage IA cancers. RESULTS: Among the 9,321 patients, we observed lower age-adjusted mortality in patients with stage I synchronous cancers (n = 937) compared to those with stage IIIA uterine (n = 531; HR, 0.45 95% CI, 0.35-0.58), stage I uterine (n = 6,919; HR, 0.74; 95% CI, 0.60-0.91), and stage I ovarian cancers (n = 934; HR, 0.52; 95% CI, 0.41-0.67). Results were similar after taking into account diagnosis year and grade, and limiting to those receiving adjuvant therapy, grade 1 or grade 3 endometrioid cancers, or stage IA cancers. CONCLUSIONS: We observed lower mortality for synchronous stage I uterine and ovarian cancers, which was not explained by younger age, earlier stage, lower grade, histology type, or adjuvant therapy. IMPACT: The possible misdiagnosis associated with clinicopathologic of synchronous uterine and ovarian cancers does not appear to worsen survival on a population level.

Drivers of racial, regional, and socioeconomic disparities in late-stage breast cancer mortality.

BACKGROUND: The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area-level socioeconomic status (SES) among women diagnosed with stage IIIB-IV BC in Georgia. METHODS: Using the Georgia Cancer Registry, 3084 patients with stage IIIB-IV primary BC (2013-2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non-Hispanic Black (NHB) versus non-Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low- versus high-SES neighborhoods by tumor, treatment, and patient characteristics. The mediating effects of specific characteristics on the association between race and BC mortality were estimated. RESULTS: Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. The authors observed mortality disparities by race (HR, 1.27; 95% CI, 1.13, 1.41) and rurality (HR, 1.14; 95% CI, 1.00, 1.30), but not by SES (HR, 1.04; 95% CI, 0.91, 1.19). In the stratified analyses, racial disparities were the most pronounced among women with HER2 overexpressing tumors (HR, 2.30; 95% CI, 1.53, 3.45). Residing in a rural county was associated with increased mortality among uninsured women (HR, 2.25; 95% CI, 1.31, 3.86), and the most pronounced SES disparities were among younger women (<40 years: HR, 1.46; 95% CI, 0.88, 2.42). CONCLUSIONS: There is considerable variation in racial, regional, and socioeconomic disparities in late-stage BC mortality by tumor, treatment, and patient characteristics.

Epidemiology beyond its limits.

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Time to Surgical Treatment and Facility Characteristics as Potential Drivers of Racial Disparities in Breast Cancer Mortality.

BACKGROUND: Black women are more likely to die of breast cancer than White women. This study evaluated the contribution of time to primary surgical management and surgical facility characteristics to racial disparities in breast cancer mortality among both Black and White women. METHODS: The study identified 2224 Black and 3787 White women with a diagnosis with stages I to III breast cancer (2010-2014). Outcomes included time to surgical treatment (> 30 days from diagnosis) and breast cancer mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) associating surgical facility characteristics with surgical delay were computed, and Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% CIs associating delay and facility characteristics with breast cancer mortality. RESULTS: Black women were two times more likely to have a surgical delay (OR, 2.15; 95% CI, 1.92-2.41) than White women. Racial disparity in surgical delay was least pronounced among women treated at a non-profit facility (OR, 1.95; 95% CI, 1.70-2.25). The estimated mortality rate for Black women was two times that for White women (HR, 2.00; 95% CI, 1.83-2.46). Racial disparities in breast cancer mortality were least pronounced among women who experienced no surgical delay (HR, 1.81; 95% CI, 1.28-2.56), received surgery at a government facility (HR, 1.31; 95% CI, 0.76-2.27), or underwent treatment at a Commission on Cancer-accredited facility (HR, 1.82; 95% CI, 1.38-2.40). CONCLUSIONS: Black women were more likely to experience a surgical delay and breast cancer death. Persistent racial disparities in breast cancer mortality were observed across facility characteristics except for government facilities.

Sampling Validation Data to Achieve a Planned Precision of the Bias-Adjusted Estimate of Effect.

Data collected from a validation substudy permit calculation of a bias-adjusted estimate of effect that is expected to equal the estimate that would have been observed had the gold standard measurement been available for the entire study population. In this paper, we develop and apply a framework for adaptive validation to determine when sufficient validation data have been collected to yield a bias-adjusted effect estimate with a prespecified level of precision. Prespecified levels of precision are decided a priori by the investigator, based on the precision of the conventional estimate and allowing for wider confidence intervals that would still be substantively meaningful. We further present an applied example of the use of this method to address exposure misclassification in a study of transmasculine/transfeminine youth and self-harm. Our method provides a novel approach to effective and efficient estimation of classification parameters as validation data accrue, with emphasis on the precision of the bias-adjusted estimate. This method can be applied within the context of any parent epidemiologic study design in which validation data will be collected and modified to meet alternative criteria given specific study or validation study objectives.

Understanding gastrointestinal cancer mortality disparities in a racially and geographically diverse population.

BACKGROUND: Gastrointestinal (GI) cancers represent a diverse group of diseases. We assessed differences in geographic and racial disparities in cancer-specific mortality across subtypes, overall and by patient characteristics, in a geographically and racially diverse US population. METHODS: Clinical, sociodemographic, and treatment characteristics for patients diagnosed during 2009-2014 with colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), or gastric cancer in Georgia were obtained from the Surveillance, Epidemiology, and End Results Program database. Patients were classified by geography (rural or urban county) and race and followed for cancer-specific death. Multivariable Cox proportional hazards models were used to calculate stratified hazard ratios (HR) and 95% confidence intervals (CIs) for associations between geography or race and cancer-specific mortality. RESULTS: Overall, 77% of the study population resided in urban counties and 33% were non-Hispanic Black (NHB). For all subtypes, NHB patients were more likely to reside in urban counties than non-Hispanic White patients. Residing in a rural county was associated with an overall increased hazard of cancer-specific mortality for HCC (HR = 1.15, 95% CI = 1.02-1.31), pancreatic (HR = 1.11, 95% CI = 1.03-1.19), and gastric cancer (HR = 1.17, 95% CI = 1.03-1.32) but near-null for CRC. Overall racial disparities were observed for CRC (HR = 1.18, 95% CI = 1.11-1.25) and HCC (HR = 1.12, 95% CI = 1.01-1.24). Geographic disparities were most pronounced among HCC patients receiving surgery. Racial disparities were pronounced among CRC patients receiving any treatment. CONCLUSION: Geographic disparities were observed for the rarer GI cancer subtypes, and racial disparities were pronounced for CRC. Treatment factors appear to largely drive both disparities.

Preexisting stress-related diagnoses and mortality: A Danish cancer cohort study.

BACKGROUND: This study evaluated the association between preexisting stress-related diagnoses and mortality in a Danish population-based cancer cohort. METHODS: This study included Danish patients with cancer diagnosed in 1995-2011 who had a stress-related diagnosis before their cancer diagnosis. Cancer patients without a prior stress-related diagnosis were matched 5:1 to the stress disorder cohort by cancer site, age group, calendar period, and sex. The 5-year cumulative incidence of cancer-specific and all-cause mortality was computed by stress-related diagnosis category. Hazard ratios and 95% confidence intervals (CIs) associating stress-related diagnoses with mortality were computed by follow-up time, stress-related diagnosis category, stage, comorbidity status, and cancer type. RESULTS: This study identified 4437 cancer patients with a preexisting stress-related diagnosis and 22,060 matched cancer cohort members. The 5-year cumulative risk of cancer-specific mortality was 33% (95% CI, 32%-35%) for those with a preexisting stress-related diagnosis and 29% (95% CI, 28%-29%) for those without a prior stress-related diagnosis. Cancer patients with a preexisting stress-related diagnosis had a 1.3 times higher cancer-specific mortality rate than the comparison cohort members (95% CI, 1.2-1.5). This increase persisted across categories of stress-related diagnosis. The association varied by stage and cancer type, with more pronounced associations found among those with a late stage at diagnosis and hematological malignancies. CONCLUSIONS: Cancer patients with preexisting stress-related diagnoses had increased rates of cancer-specific and all-cause mortality. The results suggest that psychiatric comorbidities may be an important consideration for cancer prognosis, and cancer treatment informed by a patient's history may improve outcomes.