Genetic Counseling, Testing, and Family Communication Into Survivorship After Diagnosis of Breast Cancer.

PURPOSE: To examine receipt of genetic testing and communication with relatives about results into survivorship after diagnosis of breast cancer. METHODS: Women age 20-79 years diagnosed with early-stage breast cancer in 2014-2015 and reported to the Georgia and Los Angeles County SEER registries were surveyed approximately 7 months and 6 years after diagnosis (n = 1,412). We asked about genetic counseling, testing, and communication with relatives about results. We categorized women into indications for testing on the basis of clinical guidelines at the time of diagnosis and at the time of the follow-up survey (FUPs). RESULTS: A total of 47.4% had indications for genetic testing at any time: 28.0% at baseline and an additional 19.4% at the time of the FUPs (only); 71.9% (95% CI, 67.4 to 76.4) of those with a baseline indication reported genetic testing versus 53.3% (95% CI, 47.3 to 59.2) with an indication at FUPs only and 35.0% (95% CI, 31.6 to 38.4) with no indication (P < .001). There were no significant racial or ethnic differences in receipt of testing, controlling for age and clinical indications (P = .239); results for genetic counseling were similar. Only 3.4% of survivors had direct-to-consumer genetic testing (DTCt) for cancer. Testers who reported a pathogenic variant (n = 62) were much more likely to have talked to most or all their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n = 49) or a negative finding (n = 419): 62.7% versus 38.8% and 38.0%, respectively (P < .001). CONCLUSION: Many women with indications for genetic counseling and testing into survivorship do not receive it. But those tested reach out to family members on the basis of the clinical relevance of their results. Very few patients obtained DTCt, which suggests that these tests do not substitute for clinical testing in breast cancer survivors.

Neighborhood Deprivation and Breast Cancer Mortality Among Black and White Women.

Importance: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who experience different neighborhood contexts. Accounting for interactions among neighborhood deprivation, race, and other neighborhood characteristics may enhance understanding of the association. Objective: To investigate whether neighborhood deprivation is associated with breast cancer mortality among Black and White women and whether interactions with rurality, residential mobility, and racial composition, which are markers of access, social cohesion, and segregation, respectively, modify the association. Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry (GCR) data on women with breast cancer diagnosed in 2010 to 2017 and followed-up until December 31, 2022. Data were analyzed between January 2023 and October 2023. The study included non-Hispanic Black and White women with invasive early-stage (I-IIIA) breast cancer diagnosed between 2010 and 2017 and identified through the GCR. Exposures: The Neighborhood Deprivation Index (NDI), assessed in quintiles, was derived through principal component analysis of 2011 to 2015 block group-level American Community Survey (ACS) data. Rurality, neighborhood residential mobility, and racial composition were measured using Georgia Public Health Department or ACS data. Main Outcomes and Measures: The primary outcome was breast cancer-specific mortality identified by the GCR through linkage to the Georgia vital statistics registry and National Death Index. Cox proportional hazards regression was used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and 95% CIs for the association between neighborhood deprivation and breast cancer mortality. Results: Among the 36 795 patients with breast cancer (mean [SD] age at diagnosis, 60.3 [13.1] years), 11 044 (30.0%) were non-Hispanic Black, and 25 751 (70.0%) were non-Hispanic White. During follow-up, 2942 breast cancer deaths occurred (1214 [41.3%] non-Hispanic Black women; 1728 [58.7%] non-Hispanic White women). NDI was associated with an increase in breast cancer mortality (quintile 5 vs 1, HR, 1.36; 95% CI, 1.19-1.55) in Cox proportional hazards models. The association was present only among non-Hispanic White women (quintile 5 vs 1, HR, 1.47; 95% CI, 1.21-1.79). Similar race-specific patterns were observed in jointly stratified analyses, such that NDI was associated with increased breast cancer mortality among non-Hispanic White women, but not non-Hispanic Black women, irrespective of the additional neighborhood characteristics considered. Conclusions and Relevance: In this cohort study, neighborhood deprivation was associated with increased breast cancer mortality among non-Hispanic White women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women, suggesting that factors beyond those explored here may contribute to breast cancer mortality in this racial group.

Testing a Population-Based Outreach Intervention for Ovarian Cancer Survivors to Encourage their Close Relatives to Consider Genetic Counseling.

BACKGROUND: Most relatives of women with ovarian cancer are unaware of their increased risk for cancer and their eligibility for genetic counseling. State cancer registries offer a platform to communicate about inherited risk to this population. METHODS: We conducted a two-arm randomized trial to test a theory-based communication intervention - Your Family Connects (YFC) - compared to the standard Georgia Cancer Registry (GCR) contact. A total of 1,938 eligible ovarian cancer survivors were randomly assigned to either the YFC arm (n=969) or the Standard Care arm (n=969). We assessed the number of ovarian cancer survivors and their close relatives who logged on to the study website by arm. RESULTS: Survivor reach was significantly higher in the Standard Care arm than YFC (20.8% vs 15.2%, respectively; p<0.001). However, reach to relatives was limited to listed relatives in the YFC arm (n=20, 13.2%), with little participation from those in the Standard Care arm (n=1, 0.4%). Pooling across arms, minority race, longer time since diagnosis, and older age were all significantly associated with a decreased likelihood that the survivor accessed the website. CONCLUSIONS: The YFC intervention showed lower effectiveness for engaging survivors but was more effective than Standard Care in engaging at-risk relatives. Other factors (e.g., time since diagnosis) associated with lower reach must be considered in refining future outreach approaches. IMPACT: Partnering with a state cancer registry to foster family communication about inherited cancer risk is feasible. The possibility for broad population reach warrants further testing.

Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study.

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50-70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1ß, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

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.

Health Care Access Dimensions and Racial Disparities in End-of-Life Care Quality among Patients with Ovarian Cancer.

This study investigated the association between health care access (HCA) dimensions and racial disparities in end-of-life (EOL) care quality among non-Hispanic Black (NHB), non-Hispanic White (NHW), and Hispanic patients with ovarian cancer. This retrospective cohort study used the Surveillance, Epidemiology, and End Results-linked Medicare data for women diagnosed with ovarian cancer from 2008 to 2015, ages 65 years and older. Health care affordability, accessibility, and availability measures were assessed at the census tract or regional levels, and associations between these measures and quality of EOL care were examined using multivariable-adjusted regression models, as appropriate. The final sample included 4,646 women [mean age (SD), 77.5 (7.0) years]; 87.4% NHW, 6.9% NHB, and 5.7% Hispanic. In the multivariable-adjusted models, affordability was associated with a decreased risk of intensive care unit stay [adjusted relative risk (aRR) 0.90, 95% confidence interval (CI): 0.83-0.98] and in-hospital death (aRR 0.91, 95% CI: 0.84-0.98). After adjustment for HCA dimensions, NHB patients had lower-quality EOL care compared with NHW patients, defined as: increased risk of hospitalization in the last 30 days of life (aRR 1.16, 95% CI: 1.03-1.30), no hospice care (aRR 1.23, 95% CI: 1.04-1.44), in-hospital death (aRR 1.27, 95% CI: 1.03-1.57), and higher counts of poor-quality EOL care outcomes (count ratio:1.19, 95% CI: 1.04-1.36). HCA dimensions were strong predictors of EOL care quality; however, racial disparities persisted, suggesting that additional drivers of these disparities remain to be identified. SIGNIFICANCE: Among patients with ovarian cancer, Black patients had lower-quality EOL care, even after adjusting for three structural barriers to HCA, namely affordability, availability, and accessibility. This suggests an important need to investigate the roles of yet unexplored barriers to HCA such as accommodation and acceptability, as drivers of poor-quality EOL care among Black patients with ovarian cancer.

Historical Redlining, Persistent Mortgage Discrimination, and Race in Breast Cancer Outcomes.

Importance: Inequities created by historical and contemporary mortgage discriminatory policies have implications for health disparities. The role of persistent mortgage discrimination (PMD) in breast cancer (BC) outcomes has not been studied. Objective: To estimate the race-specific association of historical redlining (HRL) with the development of BC subtypes and late-stage disease and a novel measure of PMD in BC mortality. Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry data. A total of 1764 non-Hispanic Black and White women with a BC diagnosis and residing in an area graded by the Home Owners' Loan Corporation (HOLC) in Georgia were included. Patients were excluded if they did not have a known subtype or a derived American Joint Committee on Cancer stage or if diagnosed solely by death certificate or autopsy. Participants were diagnosed with a first primary BC between January 1, 2010, to December 31, 2017, and were followed through December 31, 2019. Data were analyzed between May 1, 2022, and August 31, 2023. Exposures: Scores for HRL were examined dichotomously as less than 2.5 (ie, nonredlined) vs 2.5 or greater (ie, redlined). Contemporary mortgage discrimination (CMD) scores were calculated, and PMD index was created using the combination of HRL and CMD scores. Main Outcomes and Measures: Estrogen receptor (ER) status, late stage at diagnosis, and BC-specific death. Results: This study included 1764 women diagnosed with BC within census tracts that were HOLC graded in Georgia. Of these, 856 women (48.5%) were non-Hispanic Black and 908 (51.5%) were non-Hispanic White; 1148 (65.1%) were diagnosed at 55 years or older; 538 (30.5%) resided in tracts with HRL scores less than 2.5; and 1226 (69.5%) resided in tracts with HRL scores 2.5 or greater. Living in HRL areas with HRL scores 2.5 or greater was associated with a 62% increased odds of ER-negative BC among non-Hispanic Black women (odds ratio [OR], 1.62 [95% CI, 1.01-2.60]), a 97% increased odds of late-stage diagnosis among non-Hispanic White women (OR, 1.97 [95% CI, 1.15-3.36]), and a 60% increase in BC mortality overall (hazard ratio, 1.60 [95% CI, 1.17-2.18]). Similarly, PMD was associated with BC mortality among non-Hispanic White women but not among non-Hispanic Black women. Conclusions and Relevance: The findings of this cohort study suggest that historical racist policies and persistent discrimination have modern-day implications for BC outcomes that differ by race. These findings emphasize the need for a more nuanced investigation of the social and structural drivers of disparate BC outcomes.

Association of Major Adverse Financial Events and Later-Stage Cancer Diagnosis in the United States.

PURPOSE: This study assessed the prevalence of specific major adverse financial events (AFEs)-bankruptcies, liens, and evictions-before a cancer diagnosis and their association with later-stage cancer at diagnosis. METHODS: Patients age 20-69 years diagnosed with cancer during 2014-2015 were identified from the Seattle, Louisiana, and Georgia SEER population-based cancer registries. Registry data were linked with LexisNexis consumer data to identify patients with a history of court-documented AFEs before cancer diagnosis. The association of AFEs and later-stage cancer diagnoses (stages III/IV) was assessed using separate sex-specific multivariable logistic regression. RESULTS: Among 101,649 patients with cancer linked to LexisNexis data, 36,791 (36.2%) had a major AFE reported before diagnosis. The mean and median timing of the AFE closest to diagnosis were 93 and 77 months, respectively. AFEs were most common among non-Hispanic Black, unmarried, and low-income patients. Individuals with previous AFEs were more likely to be diagnosed with later-stage cancer than individuals with no AFE (males-odds ratio [OR], 1.09 [95% CI, 1.03 to 1.14]; P < .001; females-OR, 1.18 [95% CI, 1.13 to 1.24]; P < .0001) after adjusting for age, race, marital status, income, registry, and cancer type. Associations between AFEs prediagnosis and later-stage disease did not vary by AFE timing. CONCLUSION: One third of newly diagnosed patients with cancer had a major AFE before their diagnosis. Patients with AFEs were more likely to have later-stage diagnosis, even accounting for traditional measures of socioeconomic status that influence the stage at diagnosis. The prevalence of prediagnosis AFEs underscores financial vulnerability of patients with cancer before their diagnosis, before any subsequent financial burden associated with cancer treatment.

A Comparison of Three Area-Level Indices of Neighborhood Deprivation and Socioeconomic Status and their Applicability to Breast Cancer Mortality.

Neighborhood deprivation indices are widely used in research, but the performance of these indices has rarely been directly compared in the same analysis. We examined the Area Deprivation Index, Neighborhood Deprivation Index, and Yost index, and compared their associations with breast cancer mortality. Indices were constructed for Georgia census block groups using 2011-2015 American Community Survey data. Pearson correlation coefficients and percent agreement were calculated. Associations between each index and breast cancer mortality were estimated among 36,795 women diagnosed with breast cancer using Cox proportional hazards regression. The indices were strongly correlated (absolute value of correlation coefficients > 0.77), exhibited moderate (41.4%) agreement, and were similarly associated with a 36% increase in breast cancer mortality. The similar associations with breast cancer mortality suggest the indices measure the same underlying construct, despite only moderate agreement. By understanding their correlations, agreement, and associations with health outcomes, researchers can choose the most appropriate index for analysis.

Automated Gas Chromatography Peak Alignment: A Deep Learning Approach using Greedy Optimization and Simulation.

The clinical significance of volatile organic compounds (VOC) in detecting diseases has been established over the past decades. Gas chromatography (GC) devices enable the measurement of these VOCs. Chromatographic peak alignment is one of the important yet challenging steps in analyzing chromatogram signals. Traditional semi-automated alignment algorithms require manual intervention by an operator which is slow, expensive and inconsistent. A pipeline is proposed to train a deep-learning model from artificial chromatograms simulated from a small, annotated dataset, and a postprocessing step based on greedy optimization to align the signals.Clinical Relevance- Breath VOCs have been shown to have a significant diagnostic power for various diseases including asthma, acute respiratory distress syndrome and COVID-19. Automatic analysis of chromatograms can lead to improvements in the diagnosis and management of such diseases.

Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Your Family Connects: A Theory-Based Intervention to Encourage Communication about Possible Inherited Cancer Risk among Ovarian Cancer Survivors and Close Relatives.

INTRODUCTION: Encouraging family communication about possible genetic risk has become among the most important avenues for achieving the full potential of genomic discovery for primary and secondary prevention. Yet, effective family-wide risk communication (i.e., conveying genetic risk status and its meaning for other family members) remains a critical gap in the field. We aim to describe the iterative process of developing a scalable population-based communication outreach intervention, Your Family Connects, to reach ovarian cancer survivors and close relatives to communicate the potential for inherited risk and to consider genetic counseling. METHODS: Relational-level theories (e.g., interdependence theory) suggest that interventions to promote family cancer risk communication will be most effective if they consider the qualities of specific relationships and activate motives to preserve the relationship. Informed by these theories, we collaborated with 14 citizen scientists (survivors of ovarian cancer or relatives) and collected 261 surveys and 39 structured interviews over 12 weeks of citizen science activities in 2020. RESULTS: The citizen science findings and consideration of relational-level theories informed the content and implementation of Your Family Connects (www.yourfamilyconnects.org). CS results showed survivors favor personal contact with close relatives, but relatives were open to alternative contact methods, such as through health professionals. Recognizing the need for varied approaches based on relationship dynamics, we implemented a relative contact menu to enable survivors identify at-risk relatives and provide multiple contact options (i.e., survivor contact, health professional contact, and delayed contact). In line with relational autonomy principles, we included pros and cons for each option, assisting survivors in choosing suitable contact methods for each relative. DISCUSSION: Our developed intervention represents a novel application of relational-level theories and partnership with citizen scientists to expand genetic services reach to increase the likelihood for fair distribution of cancer genomic advances. The Your Family Connects intervention as part of a randomized trial in collaboration with the Georgia Cancer Registry compared with standard outreach.

31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration.

PURPOSE: The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. METHODS: Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score-matched to a cohort of non-31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling. RESULTS: Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients. CONCLUSION: In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.

Germline Genetic Testing After Cancer Diagnosis.

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention. Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019. Design, Setting, and Participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia. Main Outcomes and Measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing. Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type. Conclusions and Relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Environmental, social and behavioral risk factors in association with spatial clustering of childhood cancer incidence.

Childhood cancer incidence is known to vary by age, sex, and race/ethnicity, but evidence is limited regarding external risk factors. We aim to identify harmful combinations of air pollutants and other environmental and social risk factors in association with the incidence of childhood cancer based on 2003-2017 data from the Georgia Cancer Registry. We calculated the standardized incidence ratios (SIR) of Central Nervous System (CNS) tumors, leukemia and lymphomas based on age, gender and ethnic composition in each of the 159 counties in Georgia, USA. County-level information on air pollution, socioeconomic status (SES), tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied two unsupervised learning tools (self-organizing map [SOM] and exposure-continuum mapping [ECM]) to identify pertinent types of multi-exposure combinations. Spatial Bayesian Poisson models (Leroux-CAR) were fit with indicators for each multi-exposure category as exposure and SIR of childhood cancers as outcomes. We identified consistent associations of environmental (pesticide exposure) and social/behavioral stressors (low socioeconomic status, alcohol) with spatial clustering of pediatric cancer class II (lymphomas and reticuloendothelial neoplasms), but not for other cancer classes. More research is needed to identify the causal risk factors for these associations.

Primary care provider attitudes about and tendency to use non-recommended surveillance tests after curative breast cancer treatment.

PURPOSE: Little is known about the factors contributing to the receipt of non-recommended surveillance testing among early-stage breast cancer survivors. We assessed primary care providers (PCP) attitudes about and tendency to order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors post-adjuvant chemotherapy. METHODS: A stratified random sample of PCPs identified by early-stage breast cancer survivors were surveyed (N = 518, 61% response rate). PCPs were asked how likely they would be to order bone scans, imaging and/or tumor marker testing using a clinical vignette of an early-stage asymptomatic patient where these tests are non-recommended. A composite tendency to order score was created and categorized by tertiles (low, moderate, high). PCP-reported factors associated with high and moderate tendency to order non-recommended testing (vs. low) were estimated using multivariable, multinomial logistic regression. RESULTS: In this sample, 26% reported a high tendency to order non-recommended surveillance tests during survivorship for early-stage breast cancer survivors. PCPs who identified as family practice physicians and PCPs reporting more confidence in ordering surveillance testing were more likely to report a high tendency to order non-recommended testing (vs. low) ((aOR family practice 2.09, CI 1.2, 3.8; aOR more confidence 1.9, CI 1.1, 3.3). CONCLUSIONS: In this population-based sample of PCPs caring for breast cancer survivors, over a quarter of PCPs reported they would order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors. Efforts to better support PCPs and disseminate information about appropriate surveillance for cancer survivors are warranted.

Tailoring capture-recapture methods to estimate registry-based case counts based on error-prone diagnostic signals.

Surveillance research is of great importance for effective and efficient epidemiological monitoring of case counts and disease prevalence. Taking specific motivation from ongoing efforts to identify recurrent cases based on the Georgia Cancer Registry, we extend recently proposed "anchor stream" sampling design and estimation methodology. Our approach offers a more efficient and defensible alternative to traditional capture-recapture (CRC) methods by leveraging a relatively small random sample of participants whose recurrence status is obtained through a principled application of medical records abstraction. This sample is combined with one or more existing signaling data streams, which may yield data based on arbitrarily non-representative subsets of the full registry population. The key extension developed here accounts for the common problem of false positive or negative diagnostic signals from the existing data stream(s). In particular, we show that the design only requires documentation of positive signals in these non-anchor surveillance streams, and permits valid estimation of the true case count based on an estimable positive predictive value (PPV) parameter. We borrow ideas from the multiple imputation paradigm to provide accompanying standard errors, and develop an adapted Bayesian credible interval approach that yields favorable frequentist coverage properties. We demonstrate the benefits of the proposed methods through simulation studies, and provide a data example targeting estimation of the breast cancer recurrence case count among Metro Atlanta area patients from the Georgia Cancer Registry-based Cancer Recurrence Information and Surveillance Program (CRISP) database.

Characteristics of prostate cancer patients captured by facility-based versus geography-based cancer registries.

PURPOSE: We determined differences in demographics, tumor factors, and treatment patterns of prostate cancer patients in a geographic-based cancer registry based on eligibility for a facility-based cancer registry system. METHODS: We identified prostate cancer patients captured by the Surveillance, Epidemiology, and End Results (SEER) database from 2018 to 2019. Our exposure was receipt of cancer care at a facility accredited by the American College of Surgeons' Commission on Cancer (CoC) providing eligibility for inclusion in the National Cancer Database (NCDB). Outcomes included patient demographics, tumor factors (e.g., biopsy grade), and treatment with radical prostatectomy. RESULTS: We identified 113,733 prostate cancer patients of whom 65,708 (57%) were NCDB-eligible with an analytic abstract, and 11,010 (10%) were NCDB-eligible without an analytic abstract. NCDB-eligible men were younger (67.0 vs. 68.1 years, P < 0.001), less likely to be Hispanic/Latino (8.7% vs. 13.2%, P < 0.001), and more likely in a county with median income over $75,000 (40.9% vs. 30.0%, P < 0.001). NCDB eligibility varied widely by registry, from 95.9% in Connecticut to 42.6% in Utah. NCDB-ineligible patients were more likely to have unknown stage (17.2% vs. 2.9% NCDB-eligible) and missing PSA (22.9% vs 9.3% NCDB-eligible). NCDB-eligible men were less likely to have Grade Group 1 cancer on biopsy (28.2% vs. 39.2%, P < 0.001). Treatment with prostatectomy was more common among NCDB-eligible patients for low-risk (19.6% vs. 8.8%, adjusted OR 2.30, 95% CI 1.72-6.66) and high-risk tumors (43.5% vs. 26.0%, adjusted OR 1.95, 95% CI 1.33-2.86). CONCLUSION: Compared NCDB-ineligible patients, those eligible for inclusion in the NCDB have important differences in demographics, eligibility for active surveillance, and treatment patterns. Generalizations related to epidemiologic trends, practice patterns, and outcomes for this select population should be interpreted with caution.

Financial Toxicity and Its Association With Health-Related Quality of Life Among Partners of Colorectal Cancer Survivors.

Importance: Partners of colorectal cancer (CRC) survivors play a critical role in diagnosis, treatment, and survivorship. While financial toxicity (FT) is well documented among patients with CRC, little is known about long-term FT and its association with health-related quality of life (HRQoL) among their partners. Objective: To understand long-term FT and its association with HRQoL among partners of CRC survivors. Design, Setting, and Participants: This survey study incorporating a mixed-methods design consisted of a mailed dyadic survey with closed- and open-ended responses. In 2019 and 2020, we surveyed survivors who were 1 to 5 years from a stage III CRC diagnosis and included a separate survey for their partners. Patients were recruited from a rural community oncology practice in Montana, an academic cancer center in Michigan, and the Georgia Cancer Registry. Data analysis was performed from February 2022 to January 2023. Exposures: Three components of FT, including financial burden, debt, and financial worry. Main Outcomes and Measures: Financial burden was assessed with the Personal Financial Burden scale, whereas debt and financial worry were each assessed with a single survey item. We measured HRQoL using the PROMIS-29+2 Profile, version 2.1. We used multivariable regression analysis to assess associations of FT with individual domains of HRQoL. We used thematic analysis to explore partner perspectives on FT, and we merged quantitative and qualitative findings to explain the association between FT and HRQoL. Results: Of the 986 patients eligible for this study, 501 (50.8%) returned surveys. A total of 428 patients (85.4%) reported having a partner, and 311 partners (72.6%) returned surveys. Four partner surveys were returned without a corresponding patient survey, resulting in a total of 307 patient-partner dyads for this analysis. Among the 307 partners, 166 (56.1%) were aged younger than 65 years (mean [SD] age, 63.7 [11.1] years), 189 (62.6%) were women, and 263 (85.7%) were White. Most partners (209 [68.1%]) reported adverse financial outcomes. High financial burden was associated with worse HRQoL in the pain interference domain (mean [SE] score, -0.08 [0.04]; P = .03). Debt was associated with worse HRQoL in the sleep disturbance domain (-0.32 [0.15]; P = .03). High financial worry was associated with worse HRQoL in the social functioning (mean [SE] score, -0.37 [0.13]; P = .005), fatigue (-0.33 [0.15]; P = .03), and pain interference (-0.33 [0.14]; P = .02) domains. Qualitative findings revealed that in addition to systems-level factors, individual-level behavioral factors were associated with partner financial outcomes and HRQoL. Conclusions and Relevance: This survey study found that partners of CRC survivors experienced long-term FT that was associated with worse HRQoL. Multilevel interventions for both patients and partners are needed to address factors at individual and systemic levels and incorporate behavioral approaches.