Late-stage Breast Cancer Research Articles

Examining Geographic Disparity: Variation in Cancer Outcomes within Appalachia.

The Appalachian region of the United States (US) extends from the Mississippi delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed. We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017-2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004-2021 were also calculated. In 2017-2021, all-site cancer incidence (466.6; 95% confidence interval (CI), 465.5-467.6) and mortality rates (165.5; 95% CI, 164.9-166.1) among Appalachian residents were significantly higher (5.6% and 12.8%, respectively) than among non-Appalachian residents. Within Appalachia, the Central subregion-predominantly eastern Kentucky-had the highest rates of all-site cancer incidence (495.9) and mortality (201.9). In addition, the Central subregion had the highest rates of lung and colorectal cancer incidence, and the highest rates of lung, colorectal, and cervical cancer mortality. All-site cancer incidence and mortality rates among Appalachian individuals have decreased significantly since 2004 (-0.33%/year and -1.39%/year, respectively), with site-specific incidence rate decreases for late-stage lung (-2.19%/year), late-stage colorectal (-0.75%/year) and late-stage female breast (-0.35%/year) cancers in Appalachia. While cancer incidence and mortality rates are declining in Appalachia, they remain substantially higher and demonstrate slower progress than elsewhere in the US-particularly in the Central Appalachian subregion-indicating the need for targeted research to delineate and address the factors driving these cancer health disparities.

The association of travel distance and other patient characteristics with breast cancer stage at diagnosis and treatment completion at a rural Rwandan cancer facility

BackgroundButaro Cancer Center of Excellence (BCCOE) was founded to serve Rwanda’s rural low-income population, providing subsidized cancer diagnosis and treatment with transport stipends for the lowest-income patients. We examined whether travel distance to BCCOE was associated with advanced-stage diagnoses and treatment completion.MethodsWe conducted a retrospective cohort study using medical record data from BCCOE patients with pathologically-confirmed breast cancer from 2012–2016. Women with no prior surgery were included in the stage analysis; those with non-metastatic disease were included in the treatment analysis. We calculated travel distances using spatial analytic software and used multivariable logistic regression to examine the association of distance and other patient characteristics with late-stage diagnoses and treatment completion within one year of diagnosis.ResultsThe analytic cohort for stage included 426 patients; 75.1% had late-stage (stage 3 or 4) disease. In univariable analyses, patients residing in BCCOE’s surrounding district had a lower proportion of late-stage diagnoses compared to those residing outside the district (57.9% v 76.8%, p = 0.02). In adjusted analyses, odds of late-stage diagnosis were 2.46 (95% CI:1.21–5.12) times higher among those in distance quartile 4 (> 135.8 km) versus 1 (< 55.7 km); the effect of distance was less strong in sensitivity analyses excluding patients from BCCOE’s surrounding district. Patients from sectors with > 50% poverty had 2.33 times higher odds of late-stage diagnoses (95% CI:1.07–5.26) relative to those with poverty < 30%. In the treatment completion cohort (n = 348), 49.1% of patients completed surgery and chemotherapy within a year. In adjusted analyses, travel distance and poverty were not linearly associated with treatment completion.ConclusionsAt Rwanda’s first public cancer facility, sector-level poverty and longer travel distances were associated with late-stage breast cancer diagnoses, but less clearly associated with treatment completion, perhaps partly due to travel stipends provided to the lowest-income individuals undergoing treatment. Our findings support further investigation into wider use of travel stipends to facilitate early diagnosis and treatment completion.

The Role of Race/Ethnicity on the Association between Neighborhood Deprivation and Breast Cancer Outcomes among Kentucky Breast Cancer Patients years 2010-2022.

Kentucky is within the top five leading states for breast mortality nationwide. This study investigates the association between neighborhood socioeconomic disadvantage and breast cancer outcomes, including surgical treatment, radiation therapy, chemotherapy, and survival, and how associations vary by race and ethnicity in Kentucky. We conducted a retrospective cohort analysis using data from the Kentucky Cancer Registry (KCR) for breast cancer patients diagnosed between 2010 and 2017, with follow-up through December 31, 2022. We linked KCR data with census tract data to examine the relationship of Area Deprivation Index (ADI) on breast cancer outcomes. Logistic regression and Cox Proportional Hazards models analyzed binary outcomes and time-to-event data, respectively. Women in the most disadvantaged (ADI 4th quartile) neighborhoods were more likely to be diagnosed at later stages (OR: 1.26, 95% CI: 1.12-1.41) and 34% more likely to die from breast cancer (HR: 1.34, 95% CI: 1.14-1.57) after adjusting for age, race, tobacco use, tobacco pack years, marital status, insurance status, family history, stage at diagnosis, breast cancer subtype, and residence in Appalachia when compared to women living in the least disadvantaged neighborhoods (ADI 1st quartile). Women in disadvantaged neighborhoods had significantly higher odds of late-stage diagnosis and breast cancer death, regardless of race, indicating that neighborhood factors contribute to breast cancer disparities. Socioeconomic and neighborhood factors may contribute to breast cancer outcomes, suggesting the necessity for targeted interventions. Future research should explore the effectiveness of such interventions and investigate additional social determinants contributing to disparities.

Modelling the health, financial protection and equity impacts of upscaling the ACT NOW early intervention breast cancer pilot program in the Philippines: an extended cost-effectiveness analysis

IntroductionWomen in the Philippines experience significant health and economic burdens of breast cancer. The Philippines has reformed financial protection for breast cancer but does not have a national early detection...

BREAST CANCER SCREENING IN WOMEN AGED 45-65 IN SAMARKAND REGION, UZBEKISTAN: A CROSS-SECTIONAL ANALYSIS OF DATA FROM 2023

Objective: Breast cancer is a leading cause of cancer-related mortality among women globally, and early detection through screening significantly reduces morbidity and mortality. This study evaluates the outcomes of breast cancer screening programs in the Samarkand region of Uzbekistan in 2023, focusing on participation rates, detection rates, and stage distribution across 17 districts and cities. Methods: Data were collected on women aged 45–65, including annual screening targets, the number of screenings performed, diagnosed cases, and cancer stage distribution (early stages 1–2 vs. late stages 3–4). Statistical analysis was conducted to determine completion and detection rates, as well as regional disparities in screening outcomes. Results: The screening program achieved promising outcomes in participation and early-stage cancer detection, with substantial variability among districts. A higher proportion of cases were detected at stages 1–2, indicating effective early diagnosis in some areas. However, significant regional disparities in screening completion and detection highlight inequitable access to services. Novelty: This study provides a comprehensive regional analysis of breast cancer screening outcomes in Uzbekistan, emphasizing the importance of addressing disparities to improve equitable access to early diagnosis and treatment. These findings underscore the need for targeted public health interventions to enhance program effectiveness and reduce the burden of late-stage breast cancer

Evaluating Outcomes for Women with Metastatic Breast Cancer: Palliative Care Consultations, Hospital Charges, and Length of Stay.

Introduction: Women with late-stage metastatic breast cancer are at an increased risk of pain and distress from symptoms and often struggle with associated emotional and financial burden of their disease. Palliative care is known to alleviate symptom burden in patients with end-stage, terminal diseases but is often underutilized in both inpatient and outpatient settings. The current study aims to investigate the prevalence of palliative care consultation on inpatients with metastatic breast cancer and examine the association between palliative care consultation and length of hospital stay and total hospital charges. Methods: Patients diagnosed with metastatic breast cancer between 1998-2017 were abstracted from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Database (NIS). The primary outcome was the presence of a palliative care consultation (PCC) during the inpatient stay. Secondary outcomes were hospital length of stay and total hospital charges. Multivariable logistic regression was used to examine factors associated with the presence of a PCC. The relationship between PCC and hospital length of stay and total hospital charges were investigated using linear regression. Results: 513,509 cases of metastatic breast cancer were identified, 5.7% had a documented in-hospital palliative care encounter. Of those who received PCC, total hospital charges were about USD 5452 less than those who did not receive consultation. Women who received PCC had higher odds of a longer hospital stay. Predictors of PCC were older age, non-White race, and residing in a lower-income ZIP code. Conclusions: Palliative care remains to be an underutilized resource among patients with end-stage metastatic breast cancer.

Delivery of IL2RG mRNA via nanoparticles to enhance CD8+ T cell promotes anti-tumor effects against late-stage triple-negative breast cancer

BackgroundThe manipulation of CD8+ T cell functions through genetic modifications presents a novel approach to cancer immunotherapy. This study aimed to explore the effects of IL2RG-overexpressing CD8+ T cells and assess the efficacy of delivering IL2RG mRNA via nanoparticles (NPs) to the tumor microenvironment in triple-negative breast cancer (TNBC).MethodsSingle-cell RNA sequencing (scRNA-seq) was conducted on tissue from early and late-stage TNBC, followed by a meta-analysis of six breast cancer arrays from the GEO database to identify candidate genes. CRISPR/Cas9 was employed for gene knockout and overexpression in CD8+ T cells, which were then analyzed using flow cytometry, ELISA, immunofluorescence, and metabolic assays. A 3D cancer cell spheroid model was used for co-culture experiments. Lipid-coated calcium-phosphate (LCP)@IL2RG NPs were synthesized and injected into TNBC mouse models.ResultsIL2RG was identified as significantly associated with late-stage TNBC. Overexpression of IL2RG in CD8+ T cells led to increased cell activation, cytotoxicity, and glycolysis, while knockout reduced these effects. Overexpressing IL2RG in CD8+ T cells co-cultured with 3D cancer spheroids resulted in enhanced apoptosis and reduced cancer cell invasion. Injection of LCP@IL2RG NPs into TNBC mouse models significantly mitigated tumor growth.ConclusionsOverexpressing IL2RG in CD8+ T cells enhances tumor immunotherapy. Delivering IL2RG mRNA via NPs further amplifies this effect, offering a promising strategy for the treatment of late-stage TNBC.

SMARCD1 is an essential expression-restricted metastasis modifier

Breast cancer is the most frequently diagnosed cancer worldwide, constituting 15% of cases in 2023. The predominant cause of breast cancer-related mortality is metastasis, and a lack of metastasis-targeted therapies perpetuates dismal outcomes for late-stage patients. By using meiotic genetics to study inherited transcriptional network regulation, we have identified, to the best of our knowledge, a new class of “essential expression-restricted” genes as potential candidates for metastasis-targeted therapeutics. Building upon previous work implicating the CCR4-NOT RNA deadenylase complex in metastasis, we demonstrate that RNA-binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using various models and clinical data, we pinpoint Smarcd1 mRNA as a target of all three RNA-BPs. Strikingly, both high and low expression of Smarcd1 correlate with positive clinical outcomes, while intermediate expression significantly reduces the probability of survival. Applying the theory of “essential genes” from evolution, we identify 50 additional genes that require precise expression levels for metastasis to occur. Specifically, small perturbations in Smarcd1 expression significantly reduce metastasis in mouse models and alter splicing programs relevant to the ER+/HER2-enriched breast cancer. Identification subtype-specific essential expression-restricted metastasis modifiers introduces a novel class of genes that, when therapeutically “nudged” in either direction, may significantly improve late-stage breast cancer patients.

Abstract B131: Disparities in late-stage breast cancer: The impact of socioeconomic status across racial groups by healthcare utilization and community healthcare access

Abstract BACKGROUND: Late-stage breast cancer (LSBC, defined as stage 3 or 4) significantly contributes to breast cancer (BC) mortality, underscoring the importance of early detection and intervention. Understanding the individual and community factors contributing to LSBC is crucial for improving LSBC diagnoses and outcomes. OBJECTIVE: To evaluate the association between LSBC and individual demographic/socioeconomic status (SES) characteristics by race, and describe differences in individual healthcare utilization (IHU) and community healthcare access (CHA). Methods: This population-based retrospective study used demographic and SES data (age at diagnosis, marital status, years of education, income, poverty status, health insurance, and body mass index) from the Carolina BC Study Phase 3, a population-based cohort of women diagnosed with invasive BC from 2008-13. We analyzed all cases of LSBC (n=545) and stage 1 (n=1,225). Age-adjusted relative frequency differences (RFDs) and 95% confidence intervals (CIs) assessed the relationship between LSBC and SES for Black (n=835, 47.2%) and non-Black (n=935, 52.8%) women. Analyses were stratified by IHU status (High vs Low: High: Had regular pre-diagnostic care and were adherent to BC screening guidelines, &amp;gt;0.5 mammograms per year; Low: Lacked one or both forms of care); and stratified by CHA status (High vs Low), a census tract-level measure of cancer-specific healthcare infrastructure (e.g., oncologist density) and utilization (e.g., insurance rates). High CHA had either high or low infrastructure and high use; Low CHA had low infrastructure and low use. Results: Compared to non-Black women, Black women had more LSBC diagnoses (38.7% vs 23.7%), were more likely to be unmarried (59.1% vs 28.7%), have an income of &amp;lt;$50k (71.8% vs 38.2%), and be impoverished (27.0% vs 6.1%). Age at diagnosis, years of education, and income were significantly, positively associated with LSBC for all women, but the age-adjusted RFDs were greater among Blacks. After stratifying by IHU, income remained significantly associated with LSBC for Blacks with low IHU. For those with high IHU, the effects of SES on LSBC were not statistically significant. After stratifying by CHA, income and poverty status were significantly positively associated with LSBC for all women with high CHA; Marital status was significantly associated with LSBC for Blacks. Among the low CHA group, income and poverty were significantly associated for Blacks; RFDs were not estimable for non-Blacks due to small sample size (n=66). Notably, 36.5% of Blacks lived in low CHA areas compared to 7.1% of non-Blacks. Conclusion: Healthcare access exacerbates the effects of IHU but does not mitigate the impact of demographic/SES characteristics on LSBC diagnoses. Enhancing CHA alone is insufficient. Targeted interventions addressing individual and community factors are crucial to reduce LSBC diagnoses and improve outcomes, especially for Black women. Citation Format: Joel A. Begay, Brittney A. Gedeon, Matthew R. Dunn, Melissa A. Troester, Marc A. Emerson. Disparities in late-stage breast cancer: The impact of socioeconomic status across racial groups by healthcare utilization and community healthcare access [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B131.

Abstract B048: Qualitative analysis of fieldnote and interview data for planning a food bank- based breast cancer screening intervention

Abstract Among individuals and communities with low-income, the experience of food insecurity is associated with greater delays in recommended mammography screening and late-stage breast cancer at diagnosis. Community-based interventions that address barriers to breast cancer screening in diverse communities of women with food insecurity can increase screening uptake, ultimately improving cancer health equity. In partnership with Sacramento Food Bank and Family Services (SFBFS), the largest non-profit provider of social services in Sacramento County, this study identified barriers and facilitators to implementing a breast cancer screening intervention in a food distribution setting, assessing the preliminary acceptability and logistical feasibility of the proposed intervention. Qualitative data about food bank distribution events and the clients served was collected over 24 weeks using participant observation with semi-structured fieldnotes and interviews, then analyzed via directed content analysis guided by the well-defined domains and determinants in the Consolidated Framework for Implementation Research (CFIR) and coded using Dedoose software. Fieldnotes were completed for 12 community food distribution events, and 20 stakeholder interviews were conducted with purposefully sampled food bank staff (N=10) and female clients (N=10) who regularly attend events. The results of this qualitative analysis identified barriers and facilitators to implementation in all CFIR domains, describing current workflows for food distribution events and existing health education efforts, capacity, client engagement logistics and modes of delivery, and resources available or needed to support implementation. Prominent CFIR determinants included characteristics of individuals, specifically the innovation recipients’ capability and motivation to receive a breast cancer screening intervention in this context. Participants often pointed out their awareness of important preventative behaviors such as nutrition while also acknowledging barriers such as time constraints, accessibility of breast cancer screening services, and culturally-specific health beliefs and practices. Determinants in the outer setting, inner setting, innovation characteristics, and process that relate to the overall theme of sustainability were identified as potential barriers including financing, the availability of resources, internal and external pressure to change, and the process of engaging with clients while they are at the food distribution event. Facilitators included buy-in from SFBFS leadership and staff, and the benefit of collaborating with reputable local partners. Intervention format should include tailored messaging that is culturally appropriate and empowers individuals to obtain recommended screening. Content of the intervention should provide interactive assistance that facilitates local support for screening eligibility and services. Overall, there was consensus that promoting breast cancer screening in the food distribution setting was beneficial and welcomed by all stakeholders. Citation Format: Charlotte L. Kerber, Julie HT Dang, Daniel J. Pasillas-Pablo, Jocelyn T. Canty, Laura Fejerman. Qualitative analysis of fieldnote and interview data for planning a food bank- based breast cancer screening intervention [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B048.

Abstract A046: Disparities in cancer burden and survival rates in persistent poverty communities in Los Angeles County

Abstract Objective: Persistent poverty census tracts (PPT) are those with socioeconomic challenges where prolonged economic disadvantages may significantly influence health outcomes. This study examined the cancer burden and survival patterns in PPTs compared to non-PPTs in Los Angeles County (LAC) considering disparities by race/ethnicity and stage at diagnosis. Methods: A comprehensive analysis of 2012-2021 Cancer Registry data examined age-adjusted incidence rates (AAIRs) and survival rates for lung, colorectal, liver, stomach, breast, and prostate cancers, which are the Norris Comprehensive Cancer Center priority cancers. Cancer-specific data were further stratified by racial/ethnic group and stage at diagnosis, and compared across residents in PPTs, non-PPTs, and LAC overall. Survival rates were calculated using the Kaplan-Meier method and differences between groups were assessed by log-rank tests. Results: PPTs in LAC were characterized by a higher proportion of racial/ethnic minorities, lower education levels, and higher unemployment compared to non-PPTs. In all racial/ethnic groups combined, AAIRs for lung, breast, and prostate cancers were lower in PPTs than non-PPTs, whereas AAIRS for liver and stomach cancers were higher in PPTs, with no differences for colorectal cancer. Disparities emerged when considering race and ethnicity, with higher lung cancer AAIRs among Non-Hispanic White (NHW) and Black/African American (B/AA) PPT residents compared to non-PPT, while AAIRs for lung and colorectal cancers were lower among Hispanic/Latino (H/L) PPT residents compared to non-PPTs. Breast and prostate cancer AAIRs remained lower in PPTs than in non-PPTS regardless of racial/ethnic group. Patients in PPTs exhibit significantly lower five-year survival rates across all studied cancers, except stomach, compared to non-PPTs. B/AA patients showed the lowest five-year survival rates for lung and colorectal cancer, with patients in PPTs experiencing significantly lower rates than patients in non-PPTs regardless of disease stage (p &amp;lt; 0.01 for early- or late-stage). Liver cancer survival rates were notably low, especially for H/L and Asian/Pacific Islander patients in PPTs, with five-year survival for late-stage cancer at 4.9% (95%CI: 2.8-8.5) and 5.4% (95%CI: 2.1-14.0), respectively. Patients in PPTs with late-stage breast or prostate cancer exhibited significantly lower 5-year survival (compared to non-PPTs) across all race/ethnicities, with B/AA patients experiencing the lowest survival rates for breast cancer and NHW patients experiencing the lowest survival rates for prostate cancer. Conclusions: Cancer outcomes for patients in PPTs were significantly poorer compared to those in non-PPT communities. The notably lower AAIRs in PPTs versus non-PPTs for more screen-able cancers, such as breast, prostate, and early-stage colorectal cancer, suggest a need for greater efforts to provide access to routine screening in areas affected by persistent poverty, though other causes cannot be ruled out. Citation Format: Miriam L Gorbatov, Joel S. Mendez, Myles Cockburn, Laura K. Thompson, Lihua Liu, Jennifer Tsui, Kali Zhou, V. Wendy Setiawan, Chanita Hughes-Halbert, Mariana C. Stern. Disparities in cancer burden and survival rates in persistent poverty communities in Los Angeles County [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A046.

Fluorinated N-Heterocyclic Carbene Silver(I) Complexes with High Cancer Cell Selectivity.

This work presents the synthesis of five new functionalized (benz)imidazolium N-heterocyclic (NHC) ligands (L) and four new (benz)imidazole silver(I) NHC (Ag(I)-NHC) complexes of mononuclear [Ag(L)2](PF6) or binuclear [Ag2(L)2](PF6)2 type. The complexes have been fully characterized, including single crystal X-ray diffraction of three new structures. The complexes and their corresponding free NHC ligands have been screened against breast cancer and noncancerous cell lines, showing the mononuclear benzimidazole complex has the highest activity, while the binuclear benzimidazole complex has the highest cancer cell selectivity. The silver uptake was measured by ICP-MS and highlights a strong link between cytotoxicity and cellular uptake. DNA interaction studies, molecular docking, and evaluation of reactive oxygen species (ROS) have been conducted for the most promising complexes to identify modes of action. Overall, the binuclear benzimidazole complex is the most selective and promising candidate against the MDA-MD-231 (breast cancer) cell line and has potential to be developed for treatment of late-stage breast cancers.

Cancer-specific alterations in nuclear matrix proteins determined by multi-omics analyses of ductal carcinoma in situ.

Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC. Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS. Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques. These genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment.

Development of Sub-County Cancer Reporting Zones in Delaware and Example Use Case for Targeted Interventions.

To describe the Delaware Cancer Registry (DCR)'s participation in the National Cancer Institute (NCI)/North American Association of Central Cancer Registries (NAACCR) Zone Design Project to create sub-county geographic areas ("zones") for use in cancer reporting and geospatial analysis. DCR and other stakeholders reviewed up to ten unique zone configurations for each of Delaware's three counties. The zone configurations were created using AZTool and were set to optimize three objectives: create zones that have a minimum and target population of 50,000; are homogenous based on the variables of percent minority, percent below poverty, and percent urban; and are as compact as possible. The DCR sent a survey to stakeholders to provide input on their preferred zone configuration for each county. Following the final selection of zones, the DCR utilized the geographies for calculating overall and late-stage breast cancer incidence statistics and created choropleth maps to visualize the rates by quintiles. The final selections resulted in a total of 15 zones for Delaware, with three in Kent County, nine in New Castle County, and three in Sussex County. The zones ranged in population size from 54,013 to 67,693 people. Zones with higher late-stage breast cancer incidence rates included those near the areas of Wilmington, Middletown, and between Milford and Georgetown. Comparing results of overall breast cancer incidence rates by zone with late-stage rates by zone, there were areas that had lower relative overall breast cancer incidence rates but were relatively higher for late-stage rates by zones or vice versa. Aggregating census tracts into zones allows for reporting reliable cancer rates at sub-county levels, which is instrumental in conveying meaningful information about regional cancer trends to stakeholders and the public. Delaware will be able to utilize zone-level cancer information to provide targeted interventions and outreach initiatives.

Reducing Breast Cancer Disparities with Precision Public Health: A New Strategy to Improve Prevention and Advance Health Equity in Delaware Hotspots.

While Black and White women are diagnosed with breast cancer (BC) at similar rates, Black women die from BC at a 40% higher rate. This disparity is even more pronounced for younger Black women, who die from BC at nearly twice the rate as younger White women. Black-White differences in BC mortality are largely attributable to health care and tumor biology factors. Black women face greater barriers to accessing BC screening and are twice as likely to be diagnosed with the aggressive triple-negative breast cancer (TNBC) subtype. Delaware leads the US for the incidence of late-stage BC diagnosed among younger women and TNBC. This commentary begins with a discussion of precision public health, an emerging framework that builds on and complements recent advances in precision medicine. Next, a new precision public health initiative designed to reduce BC disparities in Delaware by targeting local hotspots with prevention interventions is presented. Finally, next steps are considered for implementation, evaluation, and new research activities.

PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8+ T cell suppression.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by metabolic dysregulation. Tumor cell immune escape plays an indispensable role in the development of TNBC tumors. Furthermore, in the abstract, we explicitly mention the techniques used and enhance the clarity and impact of our findings. "Based on bioinformatics analysis results, we utilized CRISPR/Cas9 technology to knockout the target gene and established a mouse model of breast cancer. Through experiments such as CCK8, scratch assay, and Transwell assay, we further investigated the impact of target gene knockout on the malignant behavior of tumor cells. Subsequently, we conducted immunohistochemistry and Western Blot experiments to study the expression of macrophage polarization and infiltration-related markers and evaluate the effect of the target gene on macrophage polarization. Next, through co-culture experiments, we simulated the tumor microenvironment and used immunohistochemistry staining to observe and analyze the distribution and activation status of M2 macrophages and CD8+ T cells in the co-culture system. We validated in vivo experiments the molecular mechanism by which the target gene regulates immune cell impact on TNBC progression.

Associations Between Perceived Discrimination, Screening Mammography, and Breast Cancer Stage at Diagnosis: A Prospective Cohort Analysis

BackgroundDespite higher breast cancer screening rates, black women still are more likely to have late-stage disease diagnosed. This disparity is influenced in part by structural and interpersonal racism. This prospective study sought to determine how interpersonal factors, including perceived discrimination, influence screening and stage of disease at diagnosis.MethodsA prospective cohort study analyzed adult women with stages I to IV breast cancer from the Miami Breast Cancer Disparities Study. Perceived discrimination and mistrust of providers were assessed using previously validated questionnaires. Multivariable logistic regression was used to evaluate the odds of screening mammography utilization and late-stage breast cancer at diagnosis.ResultsThe study enrolled 342 patients (54.4 % Hispanic, 15.8 % white, and 17.3 % black). Multivariate regression, after control for both individual- and neighborhood-level factors, showed that a higher level of perceived discrimination was associated with greater odds of late-stage disease (adjusted odds ratio [aOR], 1.06; range, 1.01–1.12); p = 0.022) and lower odds of screening mammography (aOR, 0.96; range, 0.92–0.99; p = 0.046). A higher level of perceived discrimination also was negatively correlated with multiple measures of provider trust.DiscussionThis study identified that high perceived level of discrimination is associated with decreased odds of ever having a screening mammogram and increased odds of late-stage disease. Efforts are needed to reach women who experience perceived discrimination and to improve the patient–provider trust relationship because these may be modifiable risk factors for barriers to screening and late-stage disease presentation, which ultimately have an impact on breast cancer survival.

Patient-Reported Outcomes Improve Following Mastectomy for Early-Stage Breast Cancer in Nigeria: Pilot Experience Using a Translated and Validated BREAST-Q

PURPOSE Mastectomy without reconstruction is recommended for most Nigerian women with non-metastatic breast cancer (BC), but only 43% receive surgery, partly due to psychosocial factors. Patient-reported outcome measures (PROMs) are valuable tools for improving patient-centered care. BREAST-Q is a validated PROM for evaluating satisfaction and health-related quality of life after BC surgery. This research aimed to measure the effect of mastectomy on PROMs across BC stages in Nigeria, using BREAST-Q for the first time in this setting. METHODS A psychometrically validated, Yoruba version of the BREAST-Q mastectomy module was administered pre-operatively and at multiple time-points post-operatively to Nigerian women with non-metastatic BC undergoing mastectomy at three academic institutions. Domains: psychosocial well-being, physical well-being chest, sexual well-being and satisfaction with breasts, had both pre-and post-operative applicability. BREAST-Q scores were transformed into RASCH equivalents (0=worst, 100=best). Differences between scores pre-operatively and at 6-months post-operatively were compared using a paired t-test within early-stage (I/II) and late-stage (III) cohorts. RESULTS 108 patients had a median age of 50 (IQR 43, 59). 102 had documented stage: I–5 (5%), II–42 (41%), and III–55 (54%). 90 (83%) received neoadjuvant chemotherapy. 12 (11%) received post-mastectomy radiation. Mean pre-operative BREAST-Q scores across all domains were lower for early- vs. late-stage disease. Patients with early-stage BC had significantly higher mean BREAST-Q scores at 6-months post-operatively than pre-operatively in three of four domains: psychosocial well-being (pre-op: 60/post-op: 67, p-value=0.024), physical well-being chest (pre-op: 13/post-op: 27, p-value&lt;0.001), and satisfaction with breasts (pre-op: 55/post-op: 65, p-value=0.031). Sexual well-being was not significantly different between time-points (pre-op: 29/post-op: 24, p-value=0.3). In patients with late-stage BC, psychosocial well-being (pre-op: 66/post-op: 67, p-value=0.6), physical well-being chest (pre-op: 22/post-op: 20, p-value=0.5), and satisfaction with breasts (pre-op: 58/post-op: 52, p-value=0.13) scores were similar pre- and 6-months post-operatively. Sexual well-being decreased significantly at 6-months (pre-op: 42/post-op: 25, p-value&lt;0.001). CONCLUSION We report the first-ever use of the BREAST-Q in Nigeria. PROMs following mastectomy were unchanged or better in most domains. Significant improvement was seen in patients with early-stage disease. These results can inform pre-operative patient counseling to guide expectations and reduce fear. Interventions to improve sexual well-being are needed for patients with late-stage disease.

Effects of housing stability and contemporary mortgage lending bias on breast cancer stage at diagnosis among older women in the United States.

Interventions aimed at upstream factors contributing to late-stage diagnoses could reduce disparities and improve breast cancer outcomes. This study examines the association between measures of housing stability and contemporary mortgage lending bias on breast cancer stage at diagnosis among older women in the United States. We studied 67,588 women aged 66-90 from the SEER-Medicare linked database (2010-2015). The primary outcome was breast cancer stage at diagnosis. Multinomial regression models adjusted for individual and neighborhood socio-economic factors were performed using a three-category outcome (stage 0, early stage, and late stage). Key census tract-level independent variables were residence in the same house as the previous year, owner-occupied homes, and an index of contemporary mortgage lending bias. In models adjusted for individual factors, higher levels of mortgage lending bias were associated with later stage diagnosis (RR = 1.10, 95% CI 1.02-1.20; RR = 1.31, 95% CI 1.16-1.49; RR = 1.41, 95% CI 1.24-1.60 for least to high, respectively). In models adjusted for individual and neighborhood socio-economic factors, moderate and high levels of mortgage lending bias were associated with later stage diagnosis (RR = 1.16, 95% CI 1.02-1.33 for moderate and RR = 1.18, 95% CI 1.02-1.37 for high). Owner occupancy and tenure were not associated with later stage diagnosis in adjusted models. Contemporary mortgage lending bias demonstrated a significant gradient relationship with later stage at diagnosis of breast cancer. Policy interventions aimed at reducing place-based mortgage disinvestment and its impacts on local resources and opportunities should be considered as part of an overall strategy to decrease late-stage breast cancer diagnosis and improve prognosis.

Retrospective analysis of factors impacting efficacy of patients with later stage breast cancer receiving neoadjuvant therapy.

e12624 Background: Neoadjuvant treatment is the current standard of care for patients with early breast cancer (EBC), especially for patients with later stage breast cancer (LBC). We conducted this retrospective study to summarize the correlation between pathologic complete response (pCR), disease-free survival (DFS), overall survival (OS) and clinical impacting factors of patients with later stage received neoadjuvant treatment. Methods: We retrospectively analyzed the clinical data of patients receiving neoadjuvant treatment at the Department of Breast Oncology, Peking University Cancer Hospital from Jan. 2013 to Feb. 2022. Statistical analyses were carried out using IBM SPSS Statistics. We calculated pCR rate, DFS and OS. Pearson’s χ2 or Fisher’s exact tests were used for comparison of categorical variables. DFS and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression was used to identify factors impacting on survival. All p values were two sided and p&lt;0.05 was considered to denote statistical significance. Results: Of 198 patients, most of them were in stage II (115/198, 58.1%), followed by stage III (79/198, 39.9%) and stage I (4/198, 2.0%), The pCR rates for different molecular subtypes were 31.6% TNBC, 29.7% for HR-Her2+ BC, 26.1% for HR+Her2+ BC and 1.3% for HR+Her2- BC, respectively (p=0.000). The median DFS of patients with or without pCR was 59.63 months (95%CI: NA-NA) and 29.83 months (95%CI: 21.31-38.35), respectively (p=0.012). DFS of patients who were cT1 [59.63 months (95%CI: 37.95-81.31)] or cT2 [39.56 months (95%CI: 24.19-54.93)] was significantly longer than that of patients who were cT3-4 [25.76 months (95%CI: 14.11-37.41), p=0.041]. Miller Payne (M-P) grade and ypTNM stage were also significantly associated with DFS in univariate analysis and in the multivariate cox regression model after adjusting for molecular subtypes. The 5-year OS were 87.0% for patients who reached pCR and 52.0% for patients who didn’t (p=0.009). Conclusions: The pCR was significantly associated with molecular subtypes. HR negativity and overexpression of Her2 were significantly associated with higher pCR rate. Patients reached pCR had longer DFS and OS. DFS was significantly associated with cT stage (T1 vs T2 vs T 3-4), ypTNM stage and M-P grade.