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.

Helicobacter pylori testing prior to or at gastric cancer diagnosis and survival in a diverse US patient population.

BACKGROUND: Gastric cancer (GC) accounts for the greatest disparity in cancer mortality between Black and White Americans. Although clinical trials have shown that Helicobacter pylori (Hp) treatment reduces risk of GC, Hp testing and treatment is not consistently performed in the US, and may offer an opportunity to improve survival. METHODS: In a diverse retrospective cohort of 99 GC cases diagnosed at Duke University from 2002-2020 (57% Black; 43% white), we examined the association of Hp testing and treatment prior to or at cancer diagnosis with overall survival using Cox regression analyses to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Overall, 62% of patients were tested for Hp prior to or at GC diagnosis. Of those, 25% tested positive and were treated < 1 year prior to or at diagnosis, 15% tested positive and were treated ≥ 1 year prior to diagnosis, 6% tested positive without evidence of treatment, and 54% tested negative. Compared to never tested, Hp testing and treatment < 1 year prior to or at diagnosis was associated with a significantly reduced likelihood of death (HR 0.21, 95% CI 0.08-0.58). The benefit of any Hp test and treat prior to or at GC diagnosis was significant even among stage IV patients only (HR, 0.22; 95% CI 0.05-0.96). CONCLUSIONS: These findings support Hp testing and treatment for patients at risk of or diagnosed with GC, and suggest Hp treatment may provide an opportunity to reduce GC mortality disparities in the US.

Surveillance Imaging after Primary Diagnosis of Ductal Carcinoma in Situ.

Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To identify uptake and determinants of surveillance imaging in women who underwent treatment for DCIS. Materials and Methods A stratified random sample of women who underwent breast-conserving surgery for primary DCIS between 2008 and 2014 was retrospectively selected from 1330 facilities in the United States. Imaging examinations were recorded from date of diagnosis until first distant recurrence, death, loss to follow-up, or end of study (November 2018). Imaging after treatment was categorized into 10 12-month periods starting 6 months after diagnosis. Primary outcome was per-period receipt of asymptomatic surveillance imaging (mammography, MRI, or US). Secondary outcome was diagnosis of ipsilateral invasive breast cancer. Multivariable logistic regression with repeated measures and generalized estimating equations was used to model receipt of imaging. Rates of diagnosis with ipsilateral invasive breast cancer were compared between women who did and those who did not undergo imaging in the 6-18-month period after diagnosis using inverse probability-weighted Kaplan-Meier estimators. Results A total of 12 559 women (median age, 60 years; IQR, 52-69 years) were evaluated. Uptake of surveillance imaging was 75% in the first period and decreased over time (P < .001). Across the first 5 years after treatment, 52% of women participated in consistent annual surveillance. Surveillance was lower in Black (adjusted odds ratio [OR], 0.80; 95% CI: 0.74, 0.88; P < .001) and Hispanic (OR, 0.82; 95% CI: 0.72, 0.94; P = .004) women than in White women. Women who underwent surveillance in the first period had a higher 6-year rate of diagnosis of invasive cancer (1.6%; 95% CI: 1.3, 1.9) than those who did not (1.1%; 95% CI: 0.7, 1.4; difference: 0.5%; 95% CI: 0.1, 1.0; P = .03). Conclusion Half of women did not consistently adhere to imaging surveillance guidelines across the first 5 years after treatment, with racial disparities in adherence rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rahbar and Dontchos in this issue.

Modifiable Barriers and Facilitators for Breast Cancer Care: A Thematic Analysis of Patient and Provider Perspectives.

INTRODUCTION: We sought to examine patient and provider perspectives regarding modifiable contributors to breast cancer treatment and to assess perceptual alignment between these two groups. MATERIALS: Participants were women≥18 y with stage 0-IV breast cancer who received all oncologic care in a single health system and physicians and advanced practice providers who provided medical, radiation, or surgical oncology care for breast cancer. All completed ∼45-min semistructured interviews that were recorded and transcribed verbatim. A 5-stage approach to thematic analysis was conducted, with emergent themes and exemplar quotes placed into clinical, psychological, social/logistical, financial, and lifestyle categories using a multilevel conceptual framework. RESULTS: Eighteen patients (9 Black, 9 White, and median age 60 y) and 10 providers (6 physicians and 4 advanced practice providers) were interviewed from May to November 2018. Both patients and providers perceived suboptimal communication, parking and transportation, and competing family-caregiving responsibilities as modifiable barriers to care. Treatment costs were cited by patients as barriers that were inadequately addressed even with referrals to financial counselors, but providers did not raise the issue of cost unless prompted by patients and did not feel prepared to discuss the topic when it arose. Providers cited obesity as a barrier to treatment, a view not shared by patients. CONCLUSIONS: Several modifiable factors were recognized by both patients and providers as either promoting or detracting from treatment receipt, but there was also significant incongruence and asymmetry. Alignment of provider and patient perceptions regarding contributors to guideline-concordant care receipt could mitigate disparities in breast cancer treatment and outcomes.

Disease characteristics and mortality among Asian women with breast cancer.

BACKGROUND: Asian women with breast cancer are often studied in aggregate, belying significant intragroup diversity. The authors sought to examine differences in breast cancer characteristics and outcomes among Asian women. METHODS: Asian, non-Hispanic Black, Hispanic, and non-Hispanic White women aged 18 years and older who were diagnosed with breast cancer from 1990 to 2016 were identified in the Surveillance, Epidemiology, and End Results 18 database. Asian patients were subclassified as Chinese, Japanese, Korean, Filipino, Vietnamese, South Asian (Asian Indian or Pakistani), Southeast Asian (SEA, i.e., Cambodian, Laotian, Hmong, or Thai), or other Asian. Unadjusted overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate adjusted OS and CSS. RESULTS: In total, 910,415 women were included (Asian, n = 63,405; Black, n = 92,226; Hispanic, n = 84,451; White, n = 670,333). Asian women had higher rates of human epidermal growth factor receptor 2 (HER2)-positive disease compared with White women (18.7% vs 13.8%) and had the highest 10-year unadjusted OS and CSS among all racial/ethnic groups (all P < .001). SEA women had the highest rates of stage IV disease at presentation, whereas Japanese women had the lowest rates (5.9% vs 2.7%; P < .001). Japanese women had the highest 10-year unadjusted CSS (89.4%; 95% confidence interval, 88.7%-90.1%) of any distinct Asian group, whereas SEA women had the worst unadjusted CSS (78%; 95% confidence interval, 74.1%-81.3%; P < .001). After adjustment, SEA women had the worst OS of any Asian group and were the only Asian group without improved OS compared with White women (reference category; P = .08). CONCLUSIONS: Breast cancer characteristics and outcomes vary significantly among Asian women. Future research should consider disaggregation by country or region of origin to identify subgroups that are at risk for worse outcomes than aggregated data may suggest. LAY SUMMARY: Asian women with breast cancer are frequently studied as a single entity. However, Asian ethnic groups differ greatly by country of origin, genetic ancestry, disease frequency, socioeconomic status, patterns of immigration, as well as dietary and cultural practices. Women of different Asian ethnicities vary significantly with regard to cancer characteristics, such as mortality and tumor subtype. Future research should disaggregate these populations to better understand, treat, and counsel Asian patients with breast cancer.

A Novel Staging System for De Novo Metastatic Breast Cancer Refines Prognostic Estimates.

OBJECTIVE: We aim to identify prognostic groups within a de novo metastatic cohort, incorporating both anatomic and biologic factors. BACKGROUND: Staging for breast cancer now includes anatomic and biologic factors, although the guidelines for stage IV disease do not account for how these factors may influence outcomes. METHODS: Adults with de novo metastatic breast cancer were selected from the National Cancer DataBase (2010-2013). Recursive partitioning analysis was used to group patients with similar overall survival (OS) based on clinical T/N stage, tumor grade, ER, PR, HER2, number of metastatic sites, and presence of bone-only metastases. Categories were created by amalgamating homogeneous groups based on 3-year OS rates (stage IVA: >50%, stage IVB: 30%-50%, stage IVC: <30%). RESULTS: 16,187 patients were identified; median follow-up was 32 months. 65.2% had 1 site of distant metastasis, and 42.9% had bone-only metastases. Recursive partitioning analysis identified the number of metastatic sites (1 vs >1) as the first stratification point, and ER status as the second stratification point for both resulting groups. Additional divisions were made based on HER2 status, PR status, cT stage, tumor grade, and presence of bone-only metastases. After bootstrapping, significant differences in 3-year OS were noted between the 3 groups [stage IVB vs IVA: HR 1.58 (95% confidence interval 1.50-1.67), stage IVC vs IVA: HR 3.54 (95% confidence interval 3.33-3.77)]. CONCLUSIONS: Both anatomic and biologic factors yielded reliable and reproducible prognostic estimates among patients with metastatic disease. These findings support formal stratification of de novo stage IV breast cancer into 3 distinct prognosis groups.

Differential alternative RNA splicing and transcription events between tumors from African American and White patients in The Cancer Genome Atlas.

Individuals of African ancestry suffer disproportionally from higher incidence, aggressiveness, and mortality for particular cancers. This disparity likely results from an interplay among differences in multiple determinants of health, including differences in tumor biology. We used The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA aggregate expression datasets and identified differential alternative RNA splicing and transcription events (ARS/T) in cancers between self-identified African American (AA) and White (W) patients. We found that retained intron events were enriched among race-related ARS/T. In addition, on average, 12% of the most highly ranked race-related ARS/T overlapped between any two analyzed cancers. Moreover, the genes undergoing race-related ARS/T functioned in cancer-promoting pathways, and a number of race-related ARS/T were associated with patient survival. We built a web-application, CanSplice, to mine genomic datasets by self-identified race. The race-related targets have the potential to aid in the development of new biomarkers and therapeutics to mitigate cancer disparity.

Patient-reported causes of distress predict disparities in time to evaluation and time to treatment after breast cancer diagnosis.

BACKGROUND: We examined whether the National Comprehensive Cancer Network distress thermometer (DT), a patient-reported outcome measure, could be used to identify levels and causes of distress associated with racial/ethnic disparities in time to care among patients with breast cancer. METHODS: We identified women aged ≥18 years with stage 0-IV breast cancer who were diagnosed in a single health system between January 2014 and July 2016. The baseline visit was defined as the first postdiagnosis, pretreatment clinical evaluation. Zero-inflated negative binomial (ZINB) regression (modeling non-zero DT scores and DT scores = 0) and logistic regression (modeling DT score ≥ 4, threshold for social services referral) were used to examine associations between baseline score (0 = none to 10 = extreme) and types of stressors (emotional, familial, practical, physical, spiritual) after adjustment for race/ethnicity and other characteristics. Linear regression with log transformation was used to identify predictors of time to evaluation and time to treatment. RESULTS: A total of 1029 women were included (median baseline DT score = 4). Emotional, physical, and practical stressors were associated with distress in both the ZINB and logistic models (all P < .05). Black patients (n = 258) were more likely to report no distress than Whites (n = 675; ZINB zero model odds ratio, 2.72; 95% CI, 1.68-4.40; P < .001) despite reporting a similar number of stressors (P = .07). Higher DT scores were associated with shorter time to evaluation and time to treatment while being Black and having physical or practical stressors were associated with delays in both (all P < .05). CONCLUSIONS: Patient-reported stressors predicted delays in time to care, but patient-reported levels of distress did not, with Black patients having delayed time to care despite reporting low levels of distress. We describe anticipatory, culturally responsive strategies for using patient-reported outcomes to address observed disparities.

Characterizing participants in the North Carolina Breast and Cervical Cancer Control Program: A retrospective review of 90,000 women.

BACKGROUND: The North Carolina Breast and Cervical Cancer Control Program (NC BCCCP) provides breast cancer screening services to underserved women to mitigate disparities in access to care. The authors sought to characterize this understudied population. METHODS: Women 21 years old or older who underwent their first breast cancer screen through NC BCCCP from 2008 to 2018 were included. Demographic factors associated with the timeline of care and odds of a breast cancer diagnosis were identified with negative binomial and logistic regression, respectively. RESULTS: Of the 88,893 women identified, 45.5% were non-Hispanic (NH) White, 30.9% were NH Black, 19.6% were Hispanic, 1.7% were American Indian, and 1.1% were Asian. Breast cancer was diagnosed in 2.5% of the women (n = 2255). Hispanic women were the least likely to be diagnosed with breast cancer (odds ratio vs NH White women, 0.40; 95% confidence interval [CI], 0.34-0.47). Among patients with breast pathology, the median time to diagnosis was 19 days (interquartile range [IQR], 10-33 days), and the time to treatment was 33 days (IQR, 19-54 days). After adjustments, a longer time to diagnosis was significantly associated with age (incidence rate ratio [IRR], 1.01; 95% CI, 1.01-1.02) and being NH Black (vs NH White; IRR, 1.17; 95% CI, 1.06-1.29). A longer time to treatment was significantly associated with age (IRR, 1.01; 95% CI, 1.01-1.01), being NH Black (vs NH White; IRR, 1.20; 95% CI, 1.10-1.31), and being Hispanic (vs NH White; IRR, 1.22; 95% CI, 1.05-1.41). CONCLUSIONS: NC BCCCP participants with breast cancer received treatment within approximately 1 month of presentation, and this finding aligns with quality care benchmarks. Nevertheless, racial/ethnic disparities in timeliness of care persist, and this suggests opportunities for improvement. LAY SUMMARY: This review of approximately 90,000 participants in a breast cancer screening program for uninsured and underinsured women highlights the importance of safety net programs in providing timely care to underserved patients. The authors found that the North Carolina Breast and Cervical Cancer Control Program met timeliness benchmarks from the Centers for Disease Control and Prevention across all racial/ethnic groups. However, non-Hispanic Black women experienced relative delays in the time to diagnosis, and both non-Hispanic Black women and Hispanic women experienced relative delays in the time to treatment. These findings demonstrate how racial/ethnic disparities in the timeliness of care can persist even within a program intended to reduce barriers to access.

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.

Baseline Colonoscopy Findings Associated With 10-Year Outcomes in a Screening Cohort Undergoing Colonoscopy Surveillance.

BACKGROUND & AIMS: Few studies have evaluated long-term outcomes of ongoing colonoscopic screening and surveillance in a screening population. We aimed to determine the 10-year risk for advanced neoplasia (defined as adenomas ≥10mm, adenomas with villous histology or high-grade dysplasia, or colorectal cancer [CRC]) and assessed whether baseline colonoscopy findings were associated with long-term outcomes. METHODS: We collected data from the Department of Veterans Affairs Cooperative Studies Program Study on 3121 asymptomatic veterans (50-75 years old) who underwent a screening colonoscopy from 1994 through 1997 at 13 medical centers and were then followed for 10 years or until death. We included 1915 subjects with at least 1 surveillance colonoscopy and estimated cumulative incidence of advanced neoplasia by Kaplan-Meier curves. We then fit a longitudinal joint model to estimate risk of advanced neoplasia at each subsequent examination after baseline, adjusting for multiple colonoscopies within individuals. RESULTS: Through 10 years of follow-up, there were 146 individuals among all baseline colonoscopy groups found to have at least 1 incident advanced neoplasia. The cumulative 10-year incidence of advanced neoplasia was highest among those with baseline CRC (43.7%; 95% CI 13.0%-74.4%), followed by those with baseline advanced adenoma (AA) (21.9%; 95% CI 15.7-28.1). The cumulative 10-year incidence of advanced neoplasia was 6.3% (95% CI 4.1%-8.5%) and 4.1% (95% CI 2.7%-5.4%) for baseline 1 to 2 small adenomas (<1cm, and without villous histology or high-grade dysplasia) and no neoplasia, respectively (log-rank P = .10). After adjusting for prior surveillance, the risk of advanced neoplasia at each subsequent examination was not significantly increased in veterans with 1 or 2 small adenomas at baseline (odds ratio 0.96; 95% CI 0.67-1.41) compared with veterans with no baseline neoplasia. CONCLUSIONS: Baseline screening colonoscopy findings associate with advanced neoplasia within 10 years. Individuals with only 1 or 2 small adenomas at baseline have a low risk of advanced neoplasia over 10 years. Alternative surveillance strategies, could be considered for these individuals.

Time to surgery among women treated with neoadjuvant systemic therapy and upfront surgery for breast cancer.

PURPOSE: Time to surgery (TTS) is a potentially modifiable factor associated with survival after breast cancer diagnosis and can serve as a proxy for quality of oncologic care coordination. We sought to determine whether factors associated with delays in TTS vary between patients who receive neoadjuvant systemic therapy (NST) vs upfront surgery and whether the impact of these delays on overall survival (OS) varies with treatment sequence. METHODS: Women ≥ 18 years old with Stage I-III breast cancer were identified in the National Cancer Database (2004-2014). Multivariate linear regression stratified by treatment sequence (upfront surgery vs NST [neoadjuvant chemotherapy {NAC}, neoadjuvant endocrine therapy {NAE}, or both {NACE}]) was used to identify factors associated with TTS. Cox proportional hazards models were used to estimate the effect of TTS on overall survival (OS). RESULTS: Of 693,469 patients, 14.8% (n = 102,326) received NST (NAC n = 85,143, NAE n = 10,004, NACE n = 7179). Non-White race/ethnicity, no or government-issued insurance, more extensive surgery (i.e., mastectomy and contralateral prophylactic mastectomy vs breast-conserving surgery), and post-mastectomy reconstruction were associated with significantly longer adjusted TTS for NAC and upfront-surgery recipients, but only upfront-surgery patients had progressively worse OS with increasing TTS (> 180 vs ≤ 30 days: HR = 1.31, all p < 0.001). CONCLUSIONS: Surgery extent, race/ethnicity, and insurance were associated with TTS across treatment groups, but longer TTS was only associated with worse OS in upfront-surgery patients. Our findings can help inform surgeon-patient communication, shared decision making, care coordination, and patients' expectations throughout both NST and in the perioperative period.

Treatment Patterns and Outcomes of Women with Breast Cancer and Supraclavicular Nodal Metastases.

BACKGROUND: In 2002, breast cancer patients with supraclavicular nodal metastases (cN3c) were downstaged from AJCC stage IV to IIIc, prompting management with locoregional treatment. We sought to estimate the impact of multimodal therapy on overall survival (OS) in a contemporary cohort of cN3c patients. METHODS: Women ≥ 18 years with cT1-T4c/cN3c invasive breast cancer who underwent systemic therapy were identified from the 2004-2016 National Cancer Database. We compared three patient cohorts: (a) cN3c + multimodal therapy (systemic therapy, surgery, and radiation); (b) cN3c + non-standard therapy; and, (c) cM1. Logistic regression identified factors associated with receipt of multimodal therapy and Kaplan-Meier was used to estimate unadjusted OS. The Cox proportional hazards model estimated effects of diagnosis and treatment on OS after adjustment. RESULTS: Overall, 1827 (3.7%) patients with cN3c disease and 46,919 (96.3%) cM1 patients were identified. Of cN3c patients, 74.5% (n = 1362) received multimodal therapy and 25.5% (n = 465) received non-standard therapy; receipt of multimodal therapy was associated with improved 5-year OS (multimodal: 59% vs. M1: 28% vs. non-standard: 28%, log-rank p < 0.001). Adjusting for covariates, non-standard therapy was associated with an increased risk of death compared with receipt of multimodal therapy (HR 2.20, 95% CI 1.71-2.83, p < 0.001). Private insurance was the only patient characteristic associated with a greater likelihood of receiving multimodal therapy (OR 2.81; 95% CI, 1.64-4.82; p < 0.001). CONCLUSION: Women with cN3c breast cancer who received multimodal therapy demonstrated improved overall survival when compared with patients undergoing non-standard therapy and those with metastatic (M1) disease. Although selection bias may contribute to worse overall survival among cN3c patients undergoing non-standard therapy, national guidelines should encourage locoregional treatment in carefully selected patients.

Implementation and Impact of a Risk-Stratified Prostate Cancer Screening Algorithm as a Clinical Decision Support Tool in a Primary Care Network.

BACKGROUND: Implementation methods of risk-stratified cancer screening guidance throughout a health care system remains understudied. OBJECTIVE: Conduct a preliminary analysis of the implementation of a risk-stratified prostate cancer screening algorithm in a single health care system. DESIGN: Comparison of men seen pre-implementation (2/1/2016-2/1/2017) vs. post-implementation (2/2/2017-2/21/2018). PARTICIPANTS: Men, aged 40-75 years, without a history of prostate cancer, who were seen by a primary care provider. INTERVENTIONS: The algorithm was integrated into two components in the electronic health record (EHR): in Health Maintenance as a personalized screening reminder and in tailored messages to providers that accompanied prostate-specific antigen (PSA) results. MAIN MEASURES: Primary outcomes: percent of men who met screening algorithm criteria; percent of men with a PSA result. Logistic repeated measures mixed models were used to test for differences in the proportion of individuals that met screening criteria in the pre- and post-implementation periods with age, race, family history, and PSA level included as covariates. KEY RESULTS: During the pre- and post-implementation periods, 49,053 and 49,980 men, respectively, were seen across 26 clinics (20.6% African American). The proportion of men who met screening algorithm criteria increased from 49.3% (pre-implementation) to 68.0% (post-implementation) (p < 0.001); this increase was observed across all races, age groups, and primary care clinics. Importantly, the percent of men who had a PSA did not change: 55.3% pre-implementation, 55.0% post-implementation. The adjusted odds of meeting algorithm-based screening was 6.5-times higher in the post-implementation period than in the pre-implementation period (95% confidence interval, 5.97 to 7.05). CONCLUSIONS: In this preliminary analysis, following implementation of an EHR-based algorithm, we observed a rapid change in practice with an increase in screening in higher-risk groups balanced with a decrease in screening in low-risk groups. Future efforts will evaluate costs and downstream outcomes of this strategy.

Mixed-Methods Study to Predict Upstaging of DCIS to Invasive Disease on Mammography.

BACKGROUND. The incidence of ductal carcinoma in situ (DCIS) has steadily increased, as have concerns regarding overtreatment. Active surveillance is a novel treatment strategy that avoids surgical excision, but identifying patients with occult invasive disease who should be excluded from active surveillance is challenging. Radiologists are not typically expected to predict the upstaging of DCIS to invasive disease, though they might be trained to perform this task. OBJECTIVE. The purpose of this study was to determine whether a mixed-methods two-stage observer study can improve radiologists' ability to predict upstaging of DCIS to invasive disease on mammography. METHODS. All cases of DCIS calcifications that underwent stereotactic biopsy between 2010 and 2015 were identified. Two cohorts were randomly generated, each containing 150 cases (120 pure DCIS cases and 30 DCIS cases upstaged to invasive disease at surgery). Nine breast radiologists reviewed the mammograms in the first cohort in a blinded fashion and scored the probability of upstaging to invasive disease. The radiologists then reviewed the cases and results collectively in a focus group to develop consensus criteria that could improve their ability to predict upstaging. The radiologists reviewed the mammograms from the second cohort in a blinded fashion and again scored the probability of upstaging. Statistical analysis compared the performances between rounds 1 and 2. RESULTS. The mean AUC for reader performance in predicting upstaging in round 1 was 0.623 (range, 0.514-0.684). In the focus group, radiologists agreed that upstaging was better predicted when an associated mass, asymmetry, or architectural distortion was present; when densely packed calcifications extended over a larger area; and when the most suspicious features were focused on rather than the most common features. Additionally, radiologists agreed that BI-RADS descriptors do not adequately characterize risk of invasion, and that microinvasive disease and smaller areas of DCIS will have poor prediction estimates. Reader performance significantly improved in round 2 (mean AUC, 0.765; range, 0.617-0.852; p = .045). CONCLUSION. A mixed-methods two-stage observer study identified factors that helped radiologists significantly improve their ability to predict upstaging of DCIS to invasive disease. CLINICAL IMPACT. Breast radiologists can be trained to better predict upstaging of DCIS to invasive disease, which may facilitate discussions with patients and referring providers.

Low-touch, team-based care for co-morbidity management in cancer patients: the ONE TEAM randomized controlled trial.

BACKGROUND: As treatments for cancer have improved, more people are surviving cancer. However, compared to people without a history of cancer, cancer survivors are more likely to die of cardiovascular disease (CVD). Increased risk for CVD-related mortality among cancer survivors is partially due to lack of medication adherence and problems that exist in care coordination between cancer specialists, primary care physicians, and cardiologists. METHODS/DESIGN: The Onco-primary care networking to support TEAM-based care (ONE TEAM) study is an 18-month cluster-randomized controlled trial with clustering at the primary care clinic level. ONE TEAM compares the provision of the iGuide intervention to patients and primary care providers versus an education-only control. For phase 1, at the patient level, the intervention includes video vignettes and a live webinar; provider-level interventions include electronic health records-based communication and case-based webinars. Participants will be enrolled from across North Carolina one of their first visits with a cancer specialist (e.g., surgeon, radiation or medical oncologist). We use a sequential multiple assignment randomized trial (SMART) design. Outcomes (measured at the patient level) will include Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of management of three CVD comorbidities using laboratory testing (glycated hemoglobin [A1c], lipid profile) and blood pressure measurements; (2) medication adherence assessed pharmacy refill data using Proportion of Days Covered (PDC); and (3) patient-provider communication (Patient-Centered Communication in Cancer Care, PCC-Ca-36). Primary care clinics in the intervention arm will be considered non-responders if 90% or more of their participating patients do not meet the modified HEDIS quality metrics at the 6-month measurement, assessed once the first enrollee from each practice reaches the 12-month mark. Non-responders will be re-randomized to either continue to receive the iGuide 1 intervention, or to receive the iGuide 2 intervention, which includes tailored videos for participants and specialist consults with primary care providers. DISCUSSION: As the population of cancer survivors grows, ONE TEAM will contribute to closing the CVD outcomes gap among cancer survivors by optimizing and integrating cancer care and primary care teams. ONE TEAM is designed so that it will be possible for others to emulate and implement at scale. TRIAL REGISTRATION: This study (NCT04258813) was registered in clinicaltrals.gov on February 6, 2020.

Factors associated with biomedical research participation within community-based samples across 3 National Cancer Institute-designated cancer centers.

BACKGROUND: Engaging diverse populations in biomedical research, including biospecimen donation, remains a national challenge. This study examined factors associated with an invitation to participate in biomedical research, intent to participate in biomedical research in the future, and participation in biomedical research and biospecimen donation among a diverse, multilingual, community-based sample across 3 distinct geographic areas. METHODS: Three National Cancer Institute-designated cancer centers engaged in community partnerships to develop and implement population health assessments, reaching a convenience sample of 4343 participants spanning their respective catchment areas. Data harmonization, multiple imputation, and multivariable logistic modeling were used. RESULTS: African Americans, Hispanic/Latinos, and other racial minority groups were more likely to be offered opportunities to participate in biomedical research compared to whites. Access to care, history of cancer, educational level, survey language, nativity, and rural residence also influenced opportunity, intent, and actual participation in biomedical research. CONCLUSIONS: Traditionally underserved racial and ethnic groups reported heightened opportunity and interest in participating in biomedical research. Well-established community partnerships and long-standing community engagement around biomedical research led to a diverse sample being reached at each site and may in part explain the current study findings. However, this study illustrates an ongoing need to establish trust and diversify biomedical research participation through innovative and tailored approaches. National Cancer Institute-designated cancer centers have the potential to increase opportunities for diverse participation in biomedical research through community partnerships and engagement. Additional work remains to identify and address system-level and individual-level barriers to participation in both clinical trials and biospecimen donation for research.

Implications for Breast Cancer Restaging Based on the 8th Edition AJCC Staging Manual.

OBJECTIVE: We assessed the changes that have resulted from the latest breast cancer staging guidelines and the potential impact on prognosis. BACKGROUND: Contemporary data suggest that combining anatomic staging and tumor biology yields a predictive synergy for determining breast cancer prognosis. This forms the basis for the American Joint Committee on Cancer's (AJCC) Staging Manual, 8th edition. We assessed the changes that have resulted from the new staging guidelines and the potential impact on prognosis. METHODS: Women with stages I to III breast cancer from 2010 to 2014 in the National Cancer Data Base were pathologically staged according to the 7th and 8th editions of the AJCC Staging Manual. Patient characteristics and restaging outcomes were summarized. Unadjusted overall survival (OS) was estimated, and differences were assessed. Cox proportional-hazards models were utilized to estimate the adjusted association of stage with OS. RESULTS: After restaging the 493,854 women identified, 6.8% were upstaged and 29.7% were downstaged. The stage changes varied by tumor histology, receptor status, tumor grade, and Oncotype DX scores (all P < 0.0001). Applying the 8th edition criteria yielded an incremental reduction in survival for each increase in stage, which was not consistently seen in the 7th edition. In a subgroup analysis based on hormone receptor (HR) status, those with stages II and III, and HR- disease had a worse OS than those with HR+ disease. CONCLUSIONS: Applying the 8th edition staging criteria resulted in a stage change for >35% of patients diagnosed with invasive breast cancer and refined OS estimates. Overall, the transition to the 8th edition is expected to better drive clinical care, treatment recommendations, and future research.

Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States.

BACKGROUND & AIMS: Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States. METHODS: We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression. RESULTS: Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007). CONCLUSIONS: In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.

Breast cancer tumor histopathology, stage at presentation, and treatment in the extremes of age.

BACKGROUND: Given presumed differences in disease severity between young (≤ 45 years) and elderly (≥ 75 years) women with breast cancer, we sought to compare tumor histopathology, stage at presentation, patterns of care, and survival at the extremes of age. METHODS: Adults with stages 0-IV breast cancer in the National Cancer Database (2004-2015) were categorized by age (18-45 years, 46-74 years, ≥ 75 years) and compared. Kaplan-Meier curves were used to visualize unadjusted overall survival (OS). A Cox proportional-hazards model was used to estimate the effect of age group, including adjustment for tumor subtype [hormone receptor [HR]+/HER2-, HER2+, triple-negative (TN)]. RESULTS: Of the 1,201,252 patients identified, 13% were ≤ 45 years and 17.5% were ≥ 75 years. Women ≤ 45 years were more likely to have higher pT/N stages and grade 3 disease compared to older patients; however, rates of de novo cM1 disease were comparable (3.7% vs 3.5%). HER2+ and TN tumors were more common in those ≤ 45 years (HER2+ : 18.6% vs 9.2%; TN: 14.9% vs 8.2%), while HR+/HER2- tumors were more likely in women ≥ 75 years (69.3% vs 51.3%) (all p < 0.001). Younger patients were more likely to undergo mastectomy vs lumpectomy (56% vs 34%), and receive chemotherapy (65.8% vs 10.2%) and radiation (56.2% vs 39.5%). After adjustment, OS was worse in older patients (older HR 2.94, CI 2.86-3.03). CONCLUSIONS: High-risk tumor subtypes and comprehensive multimodal treatment remain significantly more common among younger women (≤ 45 years) with breast cancer, yet, elderly women are similarly diagnosed with incurable de novo metastatic disease. Tailored screening and treatment strategies are critical to prevent age-related disparities in breast cancer care.