Comparison of incident breast cancer cases in the largest national US tumor registries.

BACKGROUND: This study compared incident breast cancer cases in the National Cancer Database (NCDB) and Surveillance, Epidemiology, End Results Program (SEER) to a national population cancer registry. METHODS: Patients with malignant or in situ breast cancer (BC) 2010-2019 in the NCDB and SEER were compared to the US Cancer Statistics (USCS). Case coverage was estimated as the number of patients in the NCDB/SEER as a proportion of USCS cases. RESULTS: The USCS reported 3,047,509 patients; 77.5% patients were included in the NCDB and 46.0% in SEER. Case ascertainment varied significantly by patient sex (both registries, p < .001). For males, 84.1% were captured in the NCDB, whereas only 77.5% of females were included. Case coverage in SEER was better for females than males (46.1% vs. 43.5%). Registries varied significantly by race/ethnicity (both p < .001). Case coverage in the NCDB was highest for non-Hispanic White (78.2%), non-Hispanic Black (77.7%), and non-Hispanic Asian or Pacific Islander (72.5%) BC patients, and lowest for Hispanic (56.4%) and non-Hispanic American Indian/Alaska Native (41.1%) patients. In SEER, case coverage was highest for non-Hispanic Asian or Pacific Islander (78.1%) and Hispanic (69.6%) patients and it was significantly lower for all other subgroups (non-Hispanic Black, 44.8%; non-Hispanic White, 42.4%; and non-Hispanic American Indian/Alaska Native, 36.6%). CONCLUSIONS: National US tumor registries provide data for a large sampling of breast cancer patients, yet significant differences in case coverage were observed based on age, sex, and race/ethnicity. These findings suggest that analyses using these data sets and interpretation of findings should account for these meaningful variances.

Insulin Resistance in Women Correlates with Chromatin Histone Lysine Acetylation, Inflammatory Signaling, and Accelerated Aging.

BACKGROUND: Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac. METHODS: Building on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women. RESULTS: ChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women. CONCLUSIONS: This study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Primary Care Use and 90-Day Mortality Among Older Adults Undergoing Cancer Surgery.

Importance: Multimorbidity and postoperative clinical decompensation are common among older surgical patients with cancer, highlighting the importance of primary care to optimize survival. Little is known about the association between primary care use and survivorship among older adults (aged ≥65 years) undergoing cancer surgery. Objective: To examine primary care use among older surgical patients with cancer and its association with mortality. Design, Setting, and Participants: In this retrospective cohort study, data were abstracted from the electronic health record of a single health care system for older adults undergoing cancer surgery between January 1, 2017, and December 31, 2019. There were 3 tiers of stratification: (1) patients who had a primary care practitioner (PCP) (physician, nurse practitioner, or physician assistant) vs no PCP, (2) those who had a PCP and underwent surgery in the same health system (unfragmented care) vs not (fragmented care), and (3) those who had a primary care visit within 90 postoperative days vs not. Data were analyzed between August 2023 and January 2024. Exposure: Primary care use after surgery for colorectal, head and neck, prostate, ovarian, pancreatic, breast, liver, renal cell, non-small cell lung, endometrial, gastric, or esophageal cancer. Main Outcomes and Measures: Postoperative 90-day mortality was analyzed using inverse propensity weighted Kaplan-Meier curves, with log-rank tests adjusted for propensity scores. Results: The study included 2566 older adults (mean [SEM] age, 72.9 [0.1] years; 1321 men [51.5%]). Although 2404 patients (93.7%) had health insurance coverage, 743 (28.9%) had no PCP at the time of surgery. Compared with the PCP group, the no-PCP group had a higher 90-day postoperative mortality rate (2.0% vs 3.6%, respectively; adjusted P = .03). For the 823 patients with unfragmented care, 400 (48.6%) had a primary care visit within 90 postoperative days (median time to visit, 34 days; IQR, 20-57 days). Patients who had a postoperative primary care visit were more likely to be older, have a higher comorbidity burden, have an emergency department visit, and be readmitted. However, they had a significantly lower 90-day postoperative mortality rate than those who did not have a primary care visit (0.3% vs 3.3%, respectively; adjusted P = .001). Conclusions and Relevance: These findings suggest that follow-up with primary care within 90 days after cancer surgery is associated with improved survivorship among older adults.

Prevalence of the cagA Virulence Factor Varies by Race Among Helicobacter pylori -Infected Patients Undergoing Upper Endoscopy.

INTRODUCTION: We designed a race-conscious study to assess the presence of Helicobacter pylori v irulence factor cagA in a retrospective cohort of patients with active H. pylori infection. METHODS: We compared cagA status by race in gastric tissue samples from 473 patients diagnosed with active H. pylori infection from 2015 to 2019. RESULTS: H. pylori + Black patients were 2 times more likely to be cagA + than H. pylori + White patients (82% vs 36%, P < .0001). DISCUSSION: Presence of cagA is common among endoscopy patients with active H. pylori infection; appropriate testing and treatment of H. pylori can both reduce gastric cancer risk and address health disparities.

Understanding mechanisms of racial disparities in breast cancer: an assessment of screening and regular care in the Carolina Breast Cancer Study.

PURPOSE: Screening history influences stage at detection, but regular preventive care may also influence breast tumor diagnostic characteristics. Few studies have evaluated healthcare utilization (both screening and primary care) in racially diverse screening-eligible populations. METHODS: This analysis included 2,058 women age 45-74 (49% Black) from the Carolina Breast Cancer Study, a population-based cohort of women diagnosed with invasive breast cancer between 2008 and 2013. Screening history (threshold 0.5 mammograms per year) and pre-diagnostic healthcare utilization (i.e. regular care, based on responses to "During the past ten years, who did you usually see when you were sick or needed advice about your health?") were assessed as binary exposures. The relationship between healthcare utilization and tumor characteristics were evaluated overall and race-stratified. RESULTS: Among those lacking screening, Black participants had larger tumors (5 + cm) (frequency 19.6% vs 11.5%, relative frequency difference (RFD) = 8.1%, 95% CI 2.8-13.5), but race differences were attenuated among screening-adherent participants (10.2% vs 7.0%, RFD = 3.2%, 0.2-6.2). Similar trends were observed for tumor stage and mode of detection (mammogram vs lump). Among all participants, those lacking both screening and regular care had larger tumors (21% vs 8%, RR = 2.51, 1.76-3.56) and advanced (3B +) stage (19% vs 6%, RR = 3.15, 2.15-4.63) compared to the referent category (screening-adherent and regular care). Under-use of regular care and screening was more prevalent in socioeconomically disadvantaged areas of North Carolina. CONCLUSIONS: Access to regular care is an important safeguard for earlier detection. Our data suggest that health equity interventions should prioritize both primary care and screening.

Disparities in OncotypeDx Testing and Subsequent Chemotherapy Receipt by Geography and Socioeconomic Status.

BACKGROUND: OncotypeDx is a prognostic and predictive genomic assay used in early-stage hormone receptor-positive, HER2- (HR+/HER2-) breast cancer. It is used to inform adjuvant chemotherapy decisions, but not all eligible women receive testing. We aimed to assess variation in testing by demographics and geography, and to determine whether testing was associated with chemotherapy. METHODS: For 1,615 women in the Carolina Breast Cancer Study with HR+/HER2-, Stage I-II tumors, we estimated prevalence differences (PD) and 95% confidence intervals (CI) for receipt of OncotypeDx genomic testing in association with and sociodemographic characteristics. We assessed associations between testing and chemotherapy receipt overall and by race. Finally, we calculated the proportion of eligible women receiving OncotypeDx by county-level rurality, census tract-level socioeconomic status, and Area Health Education Center regions. RESULTS: 38% (N = 609) of potentially eligible women were tested, with lower testing prevalences in Black (31%; PD, -11%; 95% CI, -16%-6%) and low-income women (24%; PD, -20%; 95% CI, -29% to -11%) relative to non-Black and higher income women. Urban participants were less likely to be tested than rural participants, though this association varied by region. Among women with low genomic risk tumors, tested participants were 29% less likely to receive chemotherapy than untested participants (95% CI, -40% to -17%). Racial differences in chemotherapy were restricted to untested women. CONCLUSIONS: Both individual and area-level socioeconomics predict likelihood of OncotypeDx testing. IMPACT: Variable adoption of OncotypeDx by socioeconomics and across geographic settings may contribute to excess chemotherapy among patients with HR+/HER2- cancers. See related In the Spotlight, p. 635.

Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer.

BACKGROUND: Studies have shown improved survival among individuals with cancer with higher levels of social support. Few studies have investigated social support and overall survival (OS) in individuals with advanced prostate cancer in an international cohort. We investigated the associations of marital status and living arrangements with OS among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer (IRONMAN). METHODS: IRONMAN is enrolling participants diagnosed with advanced prostate cancer (metastatic hormone-sensitive prostate cancer, mHSPC; castration-resistant prostate cancer, CRPC) from 16 countries. Participants in this analysis were recruited between July 2017 and January 2023. Adjusting for demographics and tumor characteristics, the associations were estimated using Cox regression and stratified by disease state (mHSPC, CRPC), age (<70, ≥70 years), and continent of enrollment (North America, Europe, Other). RESULTS: We included 2,119 participants with advanced prostate cancer, of whom 427 died during up to 5 years of follow-up (median 6 months). Two-thirds had mHSPC. Most were married/in a civil partnership (79%) and 6% were widowed. Very few married participants were living alone (1%), while most unmarried participants were living alone (70%). Married participants had better OS than unmarried participants [adjusted HR: 1.44; 95% confidence interval (CI): 1.02-2.02]. Widowed participants had the worst survival compared with married individuals (adjusted HR: 1.89; 95% CI: 1.22-2.94). CONCLUSIONS: Among those with advanced prostate cancer, unmarried and widowed participants had worse OS compared with married participants. IMPACT: This research highlighted the importance of social support in OS within this vulnerable population.