The unique risk factor profile of triple negative breast cancer: a comprehensive meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. This systematic review and meta-analysis examines whether known risk factors for breast cancer are also associated with TNBC in adult females. METHODS: EMBASE, Medline, SCOPUS, and grey literature were queried with no limit on the date or language of publication. The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OC) use, duration of OC use, use of menopausal hormone therapy (MHT), family history, body mass index (BMI), alcohol use, smoking and breast density. The main outcome of interest was TNBC. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. We estimated weighted odds ratios from random effects models to study the exposure-outcome associations. Protocol was registered under the number: PROSPERO 2021 CRD42021254594. RESULTS: Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, whereas, later age at menarche, later age at first birth and breastfeeding were protective against TNBC. Parity, MHT, alcohol, smoking, and BMI were not significantly associated with TNBC overall, but higher parity was associated with higher risk among Black women. CONCLUSION: Our findings highlight that TNBC has a distinct risk-factor profile compared to overall breast cancer. This can be the foundational work in identification of actionable TNBC risk factors to improve prevention and early detection of these poor prognosis breast tumors.

Protocol for a pragmatic stepped wedge cluster randomized clinical trial testing behavioral economic implementation strategies to increase supplemental breast MRI screening among patients with extremely dense breasts.

BACKGROUND: Increased breast density augments breast cancer risk and reduces mammography sensitivity. Supplemental breast MRI screening can significantly increase cancer detection among women with dense breasts. However, few women undergo this exam, and screening is consistently lower among racially minoritized populations. Implementation strategies informed by behavioral economics ("nudges") can promote evidence-based practices by improving clinician decision-making under conditions of uncertainty. Nudges directed toward clinicians and patients may facilitate the implementation of supplemental breast MRI. METHODS: Approximately 1600 patients identified as having extremely dense breasts after non-actionable mammograms, along with about 1100 clinicians involved with their care at 32 primary care or OB/GYN clinics across a racially diverse academically based health system, will be enrolled. A 2 × 2 randomized pragmatic trial will test nudges to patients, clinicians, both, or neither to promote supplemental breast MRI screening. Before implementation, rapid cycle approaches informed by clinician and patient experiences and behavioral economics and health equity frameworks guided nudge design. Clinicians will be clustered into clinic groups based on existing administrative departments and care patterns, and these clinic groups will be randomized to have the nudge activated at different times per a stepped wedge design. Clinicians will receive nudges integrated into the routine mammographic report or sent through electronic health record (EHR) in-basket messaging once their clinic group (i.e., wedge) is randomized to receive the intervention. Independently, patients will be randomized to receive text message nudges or not. The primary outcome will be defined as ordering or scheduling supplemental breast MRI. Secondary outcomes include MRI completion, cancer detection rates, and false-positive rates. Patient sociodemographic information and clinic-level variables will be examined as moderators of nudge effectiveness. Qualitative interviews conducted at the trial's conclusion will examine barriers and facilitators to implementation. DISCUSSION: This study will add to the growing literature on the effectiveness of behavioral economics-informed implementation strategies to promote evidence-based interventions. The design will facilitate testing the relative effects of nudges to patients and clinicians and the effects of moderators of nudge effectiveness, including key indicators of health disparities. The results may inform the introduction of low-cost, scalable implementation strategies to promote early breast cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05787249. Registered on March 28, 2023.

Genome-Wide Association Study of Breast Density among Women of African Ancestry.

Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40-85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each mammogram, the publicly available "LIBRA" software was used to quantify dense area and area percent density. We identified 34 significant loci associated with dense area and area percent density, with the strongest signals in GACAT3, CTNNA3, HSD17B6, UGDH, TAAR8, ARHGAP10, BOD1L2, and NR3C2. There was significant overlap between previously identified breast cancer SNPs and SNPs identified as associated with breast density. Our results highlight the importance of breast density GWAS among diverse populations, including African ancestry populations. They may provide novel insights into genetic factors associated with breast density and help in elucidating mechanisms by which density increases breast cancer risk.

Factors associated with shorter-interval cervical cancer screening for young women in three United States healthcare systems.

Frequently changing cervical cancer screening guidelines over the past two decades have been inconsistently adopted in the United States. Current guidelines set the recommended screening interval to three years for average-risk women aged 21-29 years. Few studies have evaluated how patient and provider factors are associated with implementation of cervical cancer screening intervals among younger women. This study evaluated multilevel factors associated with screening interval length among 69,939 women aged 21-29 years with an initial negative Pap screen between 2010 and 2015 across three large health systems in the U.S. Shorter-interval screening was defined as a second screening Pap within 2.5 years of an initial negative Pap. Mixed-effects logistic regression was performed for each site to identify provider and patient characteristics associated with shorter-interval screening. The odds of shorter-interval screening decreased over the study period across all sites, though the proportion of patients screened within 2.5 years remained between 7.5% and 20.7% across sites in 2014-2015. Patient factors including insurance, race/ethnicity, and pregnancy were associated with shorter-interval screening, though the patterns differed across sites. At one site, the variation in shorter-interval screening explained by the provider was 10.6%, whereas at the other two sites, the provider accounted for < 2% of the variation in shorter-interval screening. Our results highlight the heterogeneity in factors driving cervical cancer screening interval across health systems and point to the need for tailored approaches targeted to both providers and patients to improve guideline-concordant screening.

Breast density quantitative measures and breast cancer risk among screened Black women.

Mammographic density is a strong predictor of breast cancer but only slightly increased the discriminatory ability of existing risk prediction models in previous studies with limited racial diversity. We assessed discrimination and calibration of models consisting of the Breast Cancer Risk Assessment Tool (BCRAT), Breast Imaging-Reporting and Data System density and quantitative density measures. Patients were followed up from the date of first screening mammogram until invasive breast cancer diagnosis or 5-year follow-up. Areas under the curve for White women stayed consistently around 0.59 for all models, whereas the area under the curve increased slightly from 0.60 to 0.62 when adding dense area and area percent density to the BCRAT model for Black women. All women saw underprediction in all models, with Black women having less underprediction. Adding quantitative density to the BCRAT did not statistically significantly improve prediction for White or Black women. Future studies should evaluate whether volumetric breast density improves risk prediction.

Racial and Ethnic Disparities in Cervical Cancer Screening From Three U.S. Healthcare Settings.

INTRODUCTION: This study sought to characterize racial and ethnic disparities in cervical cancer screening and follow-up of abnormal findings across 3 U.S. healthcare settings. METHODS: Data were from 2016 to 2019 and were analyzed in 2022, reflecting sites within the Multi-level Optimization of the Cervical Cancer Screening Process in Diverse Settings & Populations Research Center, part of the Population-based Research to Optimize the Screening Process consortium, including a safety-net system in the southwestern U.S., a northwestern mixed-model system, and a northeastern integrated healthcare system. Screening uptake was evaluated among average-risk patients (i.e., no previous abnormalities) by race and ethnicity as captured in the electronic health record, using chi-square tests. Among patients with abnormal findings requiring follow-up, the proportion receiving colposcopy or biopsy within 6 months was reported. Multivariable regression was conducted to assess how clinical, socioeconomic, and structural characteristics mediate observed differences. RESULTS: Among 188,415 eligible patients, 62.8% received cervical cancer screening during the 3-year study period. Screening use was lower among non-Hispanic Black patients (53.2%) and higher among Hispanic (65.4%,) and Asian/Pacific Islander (66.5%) than among non-Hispanic White patients (63.5%, all p<0.001). Most differences were explained by the distribution of patients across sites and differences in insurance. Hispanic patients remained more likely to screen after controlling for a variety of clinical and sociodemographic factors (risk ratio=1.14, CI=1.12, 1.16). Among those receiving any screening test, Black and Hispanic patients were more likely to receive Pap-only testing (versus receiving co-testing). Follow-up from abnormal results was low for all groups (72.5%) but highest among Hispanic participants (78.8%, p<0.001). CONCLUSIONS: In a large cohort receiving care across 3 diverse healthcare settings, cervical cancer screening and follow-up were below 80% coverage targets. Lower screening for Black patients was attenuated by controlling for insurance and site of care, underscoring the role of systemic inequity. In addition, it is crucial to improve follow-up after abnormalities are identified, which was low for all populations.

Combining Molecular and Radiomic Features for Risk Assessment in Breast Cancer.

Breast cancer risk is highly variable within the population and current research is leading the shift toward personalized medicine. By accurately assessing an individual woman's risk, we can reduce the risk of over/undertreatment by preventing unnecessary procedures or by elevating screening procedures. Breast density measured from conventional mammography has been established as one of the most dominant risk factors for breast cancer; however, it is currently limited by its ability to characterize more complex breast parenchymal patterns that have been shown to provide additional information to strengthen cancer risk models. Molecular factors ranging from high penetrance, or high likelihood that a mutation will show signs and symptoms of the disease, to combinations of gene mutations with low penetrance have shown promise for augmenting risk assessment. Although imaging biomarkers and molecular biomarkers have both individually demonstrated improved performance in risk assessment, few studies have evaluated them together. This review aims to highlight the current state of the art in breast cancer risk assessment using imaging and genetic biomarkers.

Nationwide Trends and Determinants of Germline BRCA1/2 Testing in Patients With Breast and Ovarian Cancer.

BACKGROUND: Germline genetic testing (GT) for BRCA1/2 is instrumental in identifying patients with breast and ovarian cancers who are eligible for PARP inhibitors (PARPi). Little is known about recent trends and determinants of GT since PARPi were approved for these patients. PATIENTS AND METHODS: We performed a retrospective cohort study of patients in a nationwide electronic health record (EHR)-derived oncology-specific database with the following GT eligibility criteria: breast cancer diagnosed at age ≤45 years, triple-negative breast cancer diagnosed at age ≤60 years, male breast cancer, or ovarian cancer. GT within 1 year of diagnosis was assessed and stratified by tumor type. Multivariable log-binomial regressions estimated adjusted relative risks (RRs) of GT by patient and tumor characteristics. RESULTS: Among 2,982 eligible patients with breast cancer, 56.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.08; 95% CI, 1.05-1.11, for each year), independent of when PARPi were approved for BRCA1/2-mutated metastatic breast cancer in January 2018. In multivariable analyses, older age (RR, 0.93; 95% CI, 0.90-0.96, for every 5 years) and Medicare coverage (RR, 0.69; 95% CI, 0.49-0.96 vs commercial insurance) were associated with less GT. Among 5,563 eligible patients with ovarian cancer, 35.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.11; 95% CI, 1.07-1.14, for each year) that accelerated after approval of PARPi for BRCA1/2-mutated, chemotherapy-refractory ovarian cancer in December 2014 (RR, 1.42; 95% CI, 1.19-1.70). Older age (RR, 0.95; 95% CI, 0.93-0.97, for every 5 years) and Black or African American race (RR, 0.80; 95% CI, 0.65-0.98 vs White race) were associated with less GT. CONCLUSIONS: GT remains underutilized nationwide among patients with breast and ovarian cancers. Although GT has increased over time, significant disparities by age, race, and insurance status persist. Additional work is needed to design, implement, and evaluate strategies to ensure that all eligible patients receive GT.

Changes in mammographic density and risk of breast cancer among a diverse cohort of women undergoing mammography screening.

PURPOSE: Mammographic density (MD) is a strong breast cancer risk factor. MD may change over time, with potential implications for breast cancer risk. Few studies have assessed associations between MD change and breast cancer in racially diverse populations. We investigated the relationships between MD and MD change over time and breast cancer risk in a large, diverse screening cohort. MATERIALS AND METHODS: We retrospectively analyzed data from 8462 women who underwent ≥ 2 screening mammograms from Sept. 2010 to Jan. 2015 (N = 20,766 exams); 185 breast cancers were diagnosed 1-7 years after screening. Breast percent density (PD) and dense area (DA) were estimated from raw digital mammograms (Hologic Inc.) using LIBRA (v1.0.4). For each MD measure, we modeled breast density change between two sequential visits as a function of demographic and risk covariates. We used Cox regression to examine whether varying degrees of breast density change were associated with breast cancer risk, accounting for multiple exams per woman. RESULTS: PD at any screen was significantly associated with breast cancer risk (hazard ratio (HR) for PD = 1.03 (95% CI [1.01, 1.05], p < 0.0005), but neither change in breast density nor more extreme than expected changes in breast density were associated with breast cancer risk. We found no evidence of differences in density change or breast cancer risk due to density change by race. Results using DA were essentially identical. CONCLUSIONS: Using a large racially diverse cohort, we found no evidence of association between short-term change in MD and risk of breast cancer, suggesting that short-term MD change is not a strong predictor for risk.

Combining Breast Cancer Risk Prediction Models.

Accurate risk stratification is key to reducing cancer morbidity through targeted screening and preventative interventions. Multiple breast cancer risk prediction models are used in clinical practice, and often provide a range of different predictions for the same patient. Integrating information from different models may improve the accuracy of predictions, which would be valuable for both clinicians and patients. BRCAPRO is a widely used model that predicts breast cancer risk based on detailed family history information. A major limitation of this model is that it does not consider non-genetic risk factors. To address this limitation, we expand BRCAPRO by combining it with another popular existing model, BCRAT (i.e., Gail), which uses a largely complementary set of risk factors, most of them non-genetic. We consider two approaches for combining BRCAPRO and BCRAT: (1) modifying the penetrance (age-specific probability of developing cancer given genotype) functions in BRCAPRO using relative hazard estimates from BCRAT, and (2) training an ensemble model that takes BRCAPRO and BCRAT predictions as input. Using both simulated data and data from Newton-Wellesley Hospital and the Cancer Genetics Network, we show that the combination models are able to achieve performance gains over both BRCAPRO and BCRAT. In the Cancer Genetics Network cohort, we show that the proposed BRCAPRO + BCRAT penetrance modification model performs comparably to IBIS, an existing model that combines detailed family history with non-genetic risk factors.

Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child-Pugh B cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis are excluded or underrepresented in clinical trials of systemic therapies for hepatocellular carcinoma (HCC) and comparisons of available therapies are lacking. We aimed to compare overall survival for patients with HCC and Child-Pugh B cirrhosis treated with nivolumab or sorafenib as first systemic treatment. METHODS: We performed a retrospective cohort study in patients with HCC and Child-Pugh B cirrhosis treated at Veterans Affairs medical centers to compare overall survival, adverse events, and reason for discontinuation of therapy between patients treated with nivolumab or sorafenib as first systemic treatment. All statistical tests were 2-sided. RESULTS: Of those meeting inclusion criteria, 431 patients were treated with sorafenib and 79 with nivolumab. Median OS was 4.0 months (95% CI 3.5-4.8) in the sorafenib cohort and 5.0 months (95% CI 3.3-6.8) in the nivolumab cohort. In the multivariable Cox proportional hazards model, nivolumab was associated with a significantly reduced hazard of death compared to sorafenib (HR 0.69; 95% CI 0.52-0.91; p = 0.008). In a secondary analysis using propensity score methods, results did not reach statistical significance (HR 0.77; 95% CI 0.55-1.06; p = 0.11). Treatment was discontinued due to toxicity in 12% of patients receiving nivolumab compared to 36% receiving sorafenib (p = 0.001). CONCLUSION: In patients with HCC and Child-Pugh B cirrhosis, nivolumab treatment may be associated with improved overall survival and improved tolerability compared to sorafenib and should be considered for the first systemic treatment in this population.

Provider beliefs in effectiveness and recommendations for primary HPV testing in 3 health-care systems.

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers' beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P < .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care.

Distance to Multidisciplinary Team Clinic in Gaborone, Botswana, and Stage at Cervical Cancer Presentation for Women Living With and Without HIV.

PURPOSE: Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS: Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS: We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION: This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.

External Validation of a Mammography-Derived AI-Based Risk Model in a U.S. Breast Cancer Screening Cohort of White and Black Women.

Despite the demonstrated potential of artificial intelligence (AI) in breast cancer risk assessment for personalizing screening recommendations, further validation is required regarding AI model bias and generalizability. We performed external validation on a U.S. screening cohort of a mammography-derived AI breast cancer risk model originally developed for European screening cohorts. We retrospectively identified 176 breast cancers with exams 3 months to 2 years prior to cancer diagnosis and a random sample of 4963 controls from women with at least one-year negative follow-up. A risk score for each woman was calculated via the AI risk model. Age-adjusted areas under the ROC curves (AUCs) were estimated for the entire cohort and separately for White and Black women. The Gail 5-year risk model was also evaluated for comparison. The overall AUC was 0.68 (95% CIs 0.64−0.72) for all women, 0.67 (0.61−0.72) for White women, and 0.70 (0.65−0.76) for Black women. The AI risk model significantly outperformed the Gail risk model for all women p < 0.01 and for Black women p < 0.01, but not for White women p = 0.38. The performance of the mammography-derived AI risk model was comparable to previously reported European validation results; non-significantly different when comparing White and Black women; and overall, significantly higher than that of the Gail model.

Breast cancer polygenic risk scores are associated with short-term risk of poor prognosis breast cancer.

PURPOSE: Polygenic risk scores (PRS) for breast cancer may help guide screening decisions. However, few studies have examined whether PRS are associated with risk of short-term or poor prognosis breast cancers. The study purpose was to evaluate the association of the 313 SNP breast cancer PRS with 2-year risk of poor prognosis breast cancer. METHODS: We evaluated the association of breast cancer PRS with breast cancer overall, ER + and ER- breast cancer, and poor prognosis breast cancer diagnosed within 2 years of a negative mammogram among a cohort of 3657 women using logistic regression adjusted for age, breast density, race/ethnicity, year of screening, and genetic ancestry principal components. Breast cancers were considered poor prognosis if they were metastatic, positive lymph nodes, ER/PR + HER2- and > 2 cm, ER/PR/HER2-, or HER2 + and > 1 cm. RESULTS: Of the 308 breast cancers, 137 (44%) were poor prognosis. The overall breast cancer PRS was significantly associated with breast cancer diagnosis within 2 years (OR 1.39, 95% CI 1.23-1.57, p < 0.001). The breast cancer PRS was also associated specifically with diagnosis of poor prognosis disease (OR 1.24, 95% CI 1.03-1.49, p = 0.018), but was more strongly associated with good prognosis cancer (OR 1.52 95% CI 1.29-1.80 p = 3.60 × 10-7) The ER + PRS was significantly associated with ER/PR + breast cancer (OR 1.41, 95% CI 1.24-1.61, p < 0.001) and the ER- PRS was significantly associated with ER- breast cancer (OR 1.48, 95% CI 1.08-2.02, p = 0.015). CONCLUSION: Breast cancer PRS was independently and significantly associated with diagnosis of both breast cancer overall and poor prognosis breast cancer within 2 years of a negative mammogram, suggesting PRS may help guide decisions about screening intervals and supplemental screening.

Evaluating the geographic distribution of cervical cancer patients presenting to a multidisciplinary gynecologic oncology clinic in Gaborone, Botswana.

OBJECTIVE: In Botswana, cervical cancer is the leading cause of cancer death for females. With limited resources, Botswana is challenged to ensure equitable access to advanced cancer care. Botswana's capital city, Gaborone, houses the only gynecologic oncology multi-disciplinary team (MDT) and the one chemoradiation facility in the country. We aimed to identify areas where fewer women were presenting to the MDT clinic for care. METHODS: This cross-sectional study examined cervical cancer patients presenting to the MDT clinic between January 2015 and March 2020. Patients were geocoded to residential sub-districts to estimate age-standardized presentation rates. Global Moran's I and Anselin Local Moran's I tested the null hypothesis that presentation rates occurred randomly in Botswana. Community- and individual-level factors of patients living in sub-districts identified with higher (HH) and lower (LL) clusters of presentation rates were examined using ordinary least squares with a spatial weights matrix and multivariable logistic regression, respectively, with α level 0.05. RESULTS: We studied 990 patients aged 22-95 (mean: 50.6). Presentation rates were found to be geographically clustered across the country (p = 0.01). Five sub-districts were identified as clusters, two high (HH) sub-district clusters and three low (LL) sub-district clusters (mean presentation rate: 35.5 and 11.3, respectively). Presentation rates decreased with increased travel distance (p = 0.033). Patients residing in LL sub-districts more often reported abnormal vaginal bleeding (aOR: 5.62, 95% CI: 1.31-24.15) compared to patients not residing in LL sub-districts. Patients in HH sub-districts were less likely to be living with HIV (aOR: 0.59; 95% CI: 0.38-0.90) and more likely to present with late-stage cancer (aOR: 1.78; 95%CI: 1.20-2.63) compared to patients not in HH sub-districts. CONCLUSIONS: This study identified geographic clustering of cervical cancer patients presenting for care in Botswana and highlighted sub-districts with disproportionately lower presentation rates. Identified community- and individual level-factors associated with low presentation rates can inform strategies aimed at improving equitable access to cervical cancer care.

Racial Disparities in 30-Day Outcomes Following Index Admission for COVID-19.

We investigated racial disparities in a 30-day composite outcome of readmission and death among patients admitted across a 5-hospital health system following an index COVID-19 admission. A dataset of 1,174 patients admitted between March 1, 2020 and August 21, 2020 for COVID-19 was retrospectively analyzed for odds of readmission among Black patients compared to all other patients, with sequential adjustment for demographics, index admission characteristics, type of post-acute care, and comorbidities. Tabulated results demonstrated a significantly greater odds of 30-day readmission or death among Black patients (18.0% of Black patients vs. 11.3% of all other patients; Univariate Odds Ratio: 1.71, p = 0.002). Sequential adjustment via logistic regression revealed that the odds of 30-day readmission or death were significantly greater among Black patients after adjustment for demographics, index admission characteristics, and type of post-acute care, but not comorbidities. Stratification by type of post-acute care received on discharge revealed that the same disparity in odds of 30-day readmission or death existed among patients discharged home without home services, but not those discharged to home with home services or to a skilled nursing facility or acute rehab facility. Collectively, the findings suggest that weighing comorbidity burdens in post-acute care decisions may be relevant in addressing racial disparities in 30-day outcomes following discharge from an index COVID-19 admission.

Relationship of established risk factors with breast cancer subtypes.

BACKGROUND: Breast cancer is a heterogeneous disease, divided into subtypes based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Subtypes have different biology and prognosis, with accumulating evidence of different risk factors. The purpose of this study was to compare breast cancer risk factors across tumor subtypes in a large, diverse mammography population. METHODS: Women aged 40-84 without a history of breast cancer with a screening mammogram at three United States health systems from 2006 to 2015 were included. Risk factor questionnaires were completed at mammogram visit, supplemented by electronic health records. Invasive tumor subtype was defined by immunohistochemistry as ER/PR+HER2-, ER/PR+HER2+, ER, and PR-HER2+, or triple-negative breast cancer (TNBC). Cox proportional hazards models were run for each subtype. Associations of race, reproductive history, prior breast problems, family history, breast density, and body mass index (BMI) were assessed. The association of tumor subtypes with screen detection and interval cancer was assessed using logistic regression among invasive cases. RESULTS: The study population included 198,278 women with a median of 6.5 years of follow-up (IQR 4.2-9.0 years). There were 4002 invasive cancers, including 3077 (77%) ER/PR+HER2-, 300 (8%) TNBC, 342 (9%) ER/PR+HER2+, and 126 (3%) ER/PR-HER2+ subtype. In multivariate models, Black women had 2.7 times higher risk of TNBC than white women (HR = 2.67, 95% CI 1.99-3.58). Breast density was associated with increased risk of all subtypes. BMI was more strongly associated with ER/PR+HER2- and HER2+ subtypes among postmenopausal women than premenopausal women. Breast density was more strongly associated with ER/PR+HER2- and TNBC among premenopausal than postmenopausal women. TNBC was more likely to be interval cancer than other subtypes. CONCLUSIONS: These results have implications for risk assessment and understanding of the etiology of breast cancer subtypes. More research is needed to determine what factors explain the higher risk of TNBC for Black women.

Risk factors for breast cancer subtypes among Black women undergoing screening mammography.

PURPOSE: Black women are more likely than non-Hispanic White women to be diagnosed with triple negative breast cancer (TNBC), an aggressive subtype with limited treatment options. The study objective was to evaluate the associations of known breast cancer risk factors, including breast density, with TNBC among Black women. METHODS: This study included Black women who underwent screening mammography between the ages of 40-84 years at a University of Pennsylvania Health System between 2010 and 2015. Cox proportional hazard models using multiple imputation with chained equations were used to estimate hazard ratios and 95% confidence intervals for risk factors for ER/PR+/HER2- and TNBC. RESULTS: Among 25,013 Black women, there were 330 incident breast cancers (1.3%) during a mean follow-up of 5.8 years; 218 (66.1%) ER/PR+ HER- and 61 (18.1%) TNBC. Having dense breasts (heterogeneously dense or extremely dense) vs. non-dense breasts (almost entirely fatty or scattered areas of fibroglandular density) increased risk of ER/PR+/HER2- breast cancer almost 80% (HR 1.79, 95% CI 1.32-2.43) and TNBC more than twofold (HR 2.53, 1.45-4.44). Older age was associated with an increased risk for ER/PR+/HER2- (HR 1.04, 1.03-1.06) and TNBC (HR 1.03, 1.00-1.05). Having a BMI of > 30 kg/m2 was associated with an increased risk (HR 2.77, 1.05-7.30) for TNBC and an increased risk of ERPR+/HER2- breast cancer in postmenopausal but not pre-menopausal women (p-interaction = 0.016). CONCLUSION: Our results suggest that breast density and obesity are strong risk factors for TNBC among Black women. Understanding breast cancer subtype specific risk factors among Black women can help improve risk assessment.

Clinical and sociodemographic factors associated with late stage cervical cancer diagnosis in Botswana.

BACKGROUND: Cervical cancer is the leading cause of female cancer mortality in Botswana with the majority of cervical cancer patients presenting with late-stage disease. The identification of factors associated with late-stage disease could reduce the cervical cancer burden. This study aims to identify potential patient level clinical and sociodemographic factors associated with a late-stage diagnosis of cervical cancer in Botswana in order to help inform future interventions at the community and individual levels to decrease cervical cancer morbidity and mortality. RESULTS: There were 984 women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. Four hundred forty women (44.7%) presented with late-stage cervical cancer, and 674 women (69.7%) were living with HIV. The mean age at diagnosis was 50.5 years. The association between late-stage (III/IV) cervical cancer at diagnosis and patient clinical and sociodemographic factors was evaluated using multivariable logistic regression with multiple imputation. Women who reported undergoing cervical cancer screening had lower odds of late-stage disease at diagnosis (OR: 0.63, 95% CI 0.47-0.84) compared to those who did not report screening. Women who had never been married had increased odds of late-stage disease at diagnosis (OR: 1.35, 95% CI 1.02-1.86) compared to women who had been married. Women with abnormal vaginal bleeding had higher odds of late-stage disease at diagnosis (OR: 2.32, 95% CI 1.70-3.16) compared to those without abnormal vaginal bleeding. HIV was not associated with a diagnosis of late-stage cervical cancer. Rural women who consulted a traditional healer had increased odds of late-stage disease at diagnosis compared to rural women who had never consulted a traditional healer (OR: 1.61, 95% CI 1.02-2.55). CONCLUSION: Increasing education and awareness among women, regardless of their HIV status, and among providers, including traditional healers, about the benefits of cervical cancer screening and about the importance of seeking prompt medical care for abnormal vaginal bleeding, while also developing support systems for unmarried women, may help reduce cervical cancer morbidity and mortality in Botswana.