Breast Cancer Outcomes Research Articles

The EORTC 22922/10925 trial investigating regional nodal irradiation in stage I-III breast cancer: Outcomes according to locoregional and systemic therapies

The EORTC 22922/10925 trial aimed to investigate the impact on overall survival (OS) of elective internal mammary and medial supraclavicular (IM-MS) radiation therapy (RT) in breast cancer stage I–III. Surgery for the primary tumour and axillary lymph nodes, chest wall RT, boost RT after whole breast RT in breast conserving therapy (BCT), RT to operated axilla, and systemic therapy were per physician’s preference. The aim of the current analysis is to assess breast cancer outcomes according to different locoregional and systemic therapy used in the trial. Material/MethodsData with a median follow-up of 15.7 years were extracted from the trial’s case report forms. Kaplan-Meier curves of disease-free and OS and cumulative incidence curves of breast cancer events were produced. An exploratory analysis of the effect of the type of locoregional and systemic therapy on breast cancer outcomes was conducted using the Cox model or the Fine & Gray model accounting for competing risks, both models being adjusted for baseline patient and disease characteristics and treatment. The significance level was set at 5 %, 2-sided. ResultsOf the 4,004 patients included, 625 (16%) did not receive any postoperative systemic therapy, 1,185 (30%) received endocrine therapy only, 994 (25%) chemotherapy only, and 1,200 (30%) both chemotherapy and endocrine therapy, without differences between the randomisation arms.Administration and type of therapy was associated with age, menopausal status, clinical T- and N-stage and ER status (p < 0.0001). Local control was better with mastectomy (with/without postmastectomy RT) as compared to BCT, but mastectomy was associated with more distant metastasis (DM) as first event. Similarly, DM as first event occurred more in the BCT group that received a boost as compared to no boost and in those who received RT to the lower axillary level. IM-MS RT reduced significantly regional recurrences and improved disease-free survival in a sensitivity stratified analysis. OS was worse with mastectomy as compared to BCT and with irradiation of the axilla but better with sentinel node dissection and adjuvant combined chemo and hormonal therapy. ConclusionDifferent components of therapy influenced the site of first event. IM-MS RT improved outcomes in different breast cancer outcomes were most probably related that the group were balanced due to the trial arms and stratification methods.

A SRC-slug-TGFβ2 signaling axis drives poor outcomes in triple-negative breast cancers

SummaryIn our study, we focused on a particular subtype of aggressive breast cancer called Triple-Negative Breast Cancer (TNBC). We investigated a complex series of events that contribute to poor outcomes in this disease and uncovered a crucial signaling cascade driving tumor growth and progression.At the core of this signaling cascade are three key proteins: SRC, AKT, and ERK2. Together, they form a pathway that activates a transcription factor called Slug. Transcription factors act like molecular switches, controlling the expression of genes. Once Slug is activated, it strongly suppresses genes that would normally restrict cell growth and cell spread.One of the genes downregulated by Slug is TGFB2-AS1. This product of the TGFB2-AS1 gene normally controls levels of its target protein called TGF-beta2 (TGFB2), a protein which has roles in cell growth, cell migration and differentiation. Slug downregulation of TGFB2-AS1 results in higher TGFB2 levels, and this in turn contributes to the uncontrolled growth and spread of cancer cells. TGFB2, and other proteins in this pathway (SRC, AKT, ERK2, and a Slug interactor called LSD1) all maintain the stability of Slug, meaning that Slug levels remain high and drive the aggressive features of this subtype of breast cancer.Overall, our research sheds light on the intricate molecular mechanisms driving aggressive TNBC. It also identifies potential targets for future therapies, aimed at disrupting this harmful signaling pathway and potentially improving patient outcomes for this disease.

Breast cancer and cardiovascular health.

Modern cancer therapies greatly improve clinical outcomes for both early and advanced breast cancer patients. However, these advances have raised concerns about potential short- and long-term toxicities, including cardiovascular toxicities. Therefore, understanding the common risk factors and underlying pathophysiological mechanisms contributing to cardiovascular toxicity is essential to ensure best breast cancer outcomes. While cardio-oncology has emerged as a sub-speciality to address these challenges, it is essential that all cardiologists recognize and understand the cardiovascular consequences of cancer therapy. This review aims to provide a comprehensive overview of the potential adverse cardiovascular effects associated with modern breast cancer therapies. A preventive, diagnostic, and therapeutic workflow to minimize the impact of cardiovascular toxicity on patient outcomes is presented. Key aspects of this workflow include regular monitoring of cardiovascular function, early detection and management of cancer therapy-related cardiovascular toxicities, and optimization of cardiovascular risk factor control. By highlighting the gaps in knowledge in some areas, this review aims to emphasize the critical role of cardio-oncology research in ensuring the holistic well-being of patients with breast cancer.

Eating frequency, timing of meals, and sleep duration before and after a randomized controlled weight loss trial for breast cancer survivors.

To examine eating frequency, timing of meals, and sleep duration before and after a weight loss intervention for breast cancer survivors. Female breast cancer survivors (n = 159; 55 ± 9years; 31.4 ± 5.0 kg/m2; stage I-III, median [IQR] 9.5 [5.5] months post-diagnosis) participated in a randomized controlled trial of a 12-month weight loss intervention versus usual care. Eating frequency, proportion of daily calories consumed after 5 PM, eating after 8 PM, nightly fasting duration, and sleep duration were estimated and categorized based on existing associations with factors influencing breast cancer prognosis and breast cancer outcomes. These behaviors at baseline were compared to women from an Australian national survey with similar age and BMI range. Mixed-effects linear regression models were used to examine the changes in health behaviors from baseline to 18months between intervention and usual care groups. Before the trial, eating after 8 PM (67%) was higher, and short nightly fasting duration (< 13h, 83%) and long sleep duration (> 9h/day, 26%) were marginally higher, in breast cancer survivors than women in the national survey (52%, 75%, and 17%, respectively). "Less optimal" eating behaviors and sleep duration tended to co-occur. Behaviors remained unchanged over the 18-month follow-up, irrespective of the study group (p > 0.05; Cohen's effect sizes < 0.3). Later timing of eating and long sleep duration were prevalent in breast cancer survivors and continued following a weight loss intervention. Future multi-behavior interventions in breast cancer survivors should consider specific messages to target eating timing behaviors and sleep.

Abstract A058: Investigating the role of race/ethnicity on the association between neighborhood deprivation and breast cancer outcomes among Kentucky breast cancer patients years 2010-2022

Abstract Background: Despite advances in medical knowledge and treatment, disparities in breast cancer outcomes persist along demographic and socioeconomic lines. To quantify these disparities, the Area Deprivation Index (ADI) emerges as a powerful metric. It offers insights into the interplay between neighborhood socioeconomic status and breast cancer outcomes by encompassing factors pertaining to income, education, employment, and housing quality. There have been limited studies to examine the role of race and neighborhood disadvantage on specific breast cancer outcomes. Kentucky also faces a unique burden as it has the third highest breast cancer mortality rate in the United States. This study aims to examine the association between neighborhood socioeconomic disadvantage, and breast cancer outcomes including receipt of surgical treatment, radiation therapy, chemotherapy, and breast cancer-specific survival. While also examining how any associations are modified by race and ethnicity among Kentucky breast cancer patients. Methods: We conducted a retrospective cohort analysis using data from the Kentucky Cancer Registry (KCR) among breast cancer patients diagnosed between 2010 and 2017 with follow-up data through December 31, 2022. The KCR dataset was then linked with census tract data to examine ADI. We conducted consecutive multilevel logistic regression for binary outcomes and Cox Proportional hazard models using SAS (version 9.4, SAS Institute, Inc., Cary, North Carolina, USA) for time-to-event of breast cancer survival. Results: Women in the most disadvantaged quartile (4th quartile) were more likely to be Non-Hispanic Black (NH-Black), Appalachian residents, current tobacco users, divorced and using government insurance. Compared to women in the least disadvantaged neighborhoods (1st quartile) women living in the most disadvantaged neighborhoods (4th quartile) were 50% more likely to die from breast cancer (HR: 1.50, 95 CI: 1.28-1.76). Women in the most disadvantaged neighborhoods (4th quartile) were also more likely to be diagnosed at later stages (aOR:1.26, 95 CI:1.13-1.42). These associations were all observed after adjusting for age, race, tobacco use, marital status, insurance status, family history, and residence in Appalachia. Conclusions: Women living in areas of greater disadvantage had significantly increased odds of late-stage diagnosis and risk of breast cancer death regardless of race suggesting that neighborhood-level factors contribute to breast cancer disparities. Our findings underscore the need for neighborhood-level interventions to improve cancer outcomes. Citation Format: Breyanna E. Walker, Elinita Pollard, Justin Moore, Sydney Howard, Pamela Hull, Kathleen O'Connor, Samantha Jones, Lovoria Williams, Adebola Adegboyega, Veronica Jones, Eric Durban, Xiaoqin Wang, Wendi Owen. Investigating the role of race/ethnicity on the association between neighborhood deprivation and breast cancer outcomes among Kentucky breast cancer patients years 2010-2022 [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 A058.

Abstract C039: Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study

Abstract Background: Associations of nativity and breast cancer (BC) mortality are mixed in studies using cancer registry data. We examined associations in diverse women with detailed individual-level data on BC treatment and subtype. Methods: The study population included 5,718 Asian (n=722, 71% foreign-born), Hispanic (n=631, 42% foreign-born), and non-Hispanic White (n=4,365, 9% foreign-born) women from the ENCLAVE Study diagnosed with invasive BC from 1996-2013 using pooled, harmonized data from two (of three) cohorts with data on BC subtype. Data on nativity, reproductive and behavioral factors were self-reported from questionnaires; data on disease severity, BC subtype (luminal A, luminal B, Her2 expressing, triple negative breast cancer), treatment, and mortality were obtained from cancer registries and electronic health records. Recurrences were identified by recurrence algorithms and medical record review. We fit Cox proportional hazards regression models to examine associations between self-reported nativity and recurrence, BC-specific mortality, and overall mortality. Covariates included age, sociodemographic factors, disease severity, and treatment, reproductive and behavioral factors. We also examined associations by race, ethnicity, and BC subtype. Results: Compared to US-born women, foreign-born women had lower total mortality (hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.64-0.89); lower risks were suggested for recurrence (HR=0.85, 95% CI: 0.68-1.06) and breast cancer-specific mortality (HR=0.87, 95% CI: 0.66-1.14). Stratified by BC subtype, foreign- (vs. US-) born women had a lower risk of overall mortality among those with luminal A (HR=0.72, 95% CI: 0.56-0.92) and luminal B (HR=0.66, 95% CI: 0.48-0.91) but not other subtypes. Among women with luminal B BC, these associations reached statistical significance for recurrence (HR=0.65, 95% CI: 0.45-0.94) and BC-specific mortality (HR=0.53, 95% CI: 0.33-0.84). We noted no associations in other BC subtypes though analyses of less common subtypes were underpowered. Associations did not differ by race or ethnicity. Conclusion: Foreign-born women with BC had lower risk of overall mortality than US-born women. Risks of recurrence and BC-specific mortality were lower in foreign-born vs. US-born women among those with the luminal B BC subtype. Associations were not explained by behavioral or reproductive factors. Citation Format: Candyce Kroenke, Rhonda Aoki, Stacey Alexeeff, Scarlett Gomez, Bette Caan, Brittany Morey, Jacqueline Torres, Larry Kushi. Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study [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 C039.

Abstract A015: Small area-estimation for low mammography screening: Geographic and racial disparities in mammography screening, 2015 – 2022

Abstract Background: Mammography screening is associated with at least a 20% reduction in breast cancer mortality. However, there are racial/ethnic differences in breast cancer mortality. For example, non-Hispanic Black (NHB) women are significantly more likely to die of breast cancer than non-Hispanic White (NHW) women. Few studies have reported small-area estimates for mammography screening among the entire US population; differences by race were either not examined or resulted in mixed findings. The American Cancer Society (ACS) and the United States Preventive Services Taskforce (USPSTF) recommend regular mammography screening from age 40 through 74 years. The current study aims to identify areas of up-to-date mammography screening and to elucidate whether mammography screening varied by geographical location, race, or ethnicity. Methods: Mammography screening within the past 12 months was retrieved from the 2015-2022 Behavioral Risk Factor Surveillance System data. The study population consisted of adult women aged 40 and older residing within the United States. 2020 US census tract population estimates were used to generate gender (all women), race/ethnicity (NHB, NHW, non-Hispanic Asian, and Hispanic/Latina), income, and age group weights for each US census tract. Synthetic estimates of mammography screening uptake at the census tract were conducted using our novel PARIS model (Probability of mammography screening within the past year, given age, race/ethnicity, income, and state) using a multilevel logistic regression model. Regional differences in mammography screening by US Census Bureau regions and divisions were examined. Results: Up-to-date mammography among all women in the sample was 55.98% (SD = 2.07; F (3, 72429) = 2886.81, p &amp;lt; .0001). Mammography screening examined by race indicated the greatest screening rates among non-Hispanic Black women (M = 60.78, SD = 3.11) and least among Asian women (M = 48.68, SD = 3.15). Among four US Census Bureau regions, the West region had the lowest rates of mammography screening among women (M = 54.74, SD = 1.85) while the South region had the highest rates (M = 56.55, SD = 2.18; F(3, 72429) = 2886.81, p &amp;lt; .0001). After further parsing geographical units, the West Pacific region, among the 9 US Census Bureau divisions, had the lowest mammography screening (M = 54.53, SD = 1.81) while the East South Central division had the highest rates of mammography screening (M = 56.94, SD = 2.10; F(8, 72429) = 1360.60, p &amp;lt; .0001).Conclusion: Using novel geospatial methods, the current study elucidated significant differences in mammography screening by race and place. These results suggest that Black women and women living in the South have higher up-to-date mammography screening compared to other women. Thus, the existing inequities in breast cancer outcomes may be explained by differences in the cancer care continuum (delays in follow-up care, treatment, and breast cancer survival). Further examination of the interplay between screening uptake, late-stage diagnosis, and death is needed. Citation Format: Sydney P. Howard, Justin X. Moore, Elinita Pollard, Ryan Johnson, Lovoria Williams, Adebola Adegboyega, Jie Chen, Jorge Cortes, Aimee James. Small area-estimation for low mammography screening: Geographic and racial disparities in mammography screening, 2015 – 2022 [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 A015.

Abstract B156: Exploring identity-specific stressors among Black women with a family history of cancer

Abstract Background: Compared to women of other racial/ethnic groups, Black women are more likely to be diagnosed with aggressive subtypes of breast cancer (including triple-negative breast cancer), diagnosed at younger ages, diagnosed at more advanced stages, and have higher mortality rates and poorer survival outcomes. Black women also experience higher rates of breast cancer recurrence, which further exacerbates the survival disparities. These disparities are influenced by a complex interplay of genetic, environmental, and social factors, including chronic stress and discrimination. Understanding identity-specific stressors will help identify potential risk factors impacting breast cancer outcomes among Black women.Objective: This study aims to identify common stressors among Black women aged 18 to 49 with a family history of cancer, exploring potential links to breast health risk. Methods: We conducted a grounded theory study, including qualitative interviews from Black women in the Augusta, Georgia, area (N=47) discussing life as a Black woman and sources of stress. Participants with a close family history of cancer (defined as having at least one first- or second-degree relative diagnosed with cancer) were selected for this analysis (n=22). We applied the Sort &amp; Sift, Think &amp; Shift method for analysis. Results: We identified three categories in response to the research question, including healthcare access barriers and medical invalidation (particularly in rural communities), intergenerational trauma, and Strong Black Woman persona (characterized by independence, emotional suppression, and a tendency to care for others while neglecting their own needs). Participants described these categories in reference to themselves and their female family members with cancer. Participants reported stress related to jobs and caregiving responsibilities, lack of adequate social support, lack of time and finances necessary for self-care, and racial discrimination in medical settings. Conclusion: The identified stressors highlight the complex interplay between familial cancer history and daily stress experiences among Black women. These findings suggest the need for targeted interventions to mitigate stress and potentially reduce breast cancer risk. Further research is warranted to explore these themes in relation to breast cancer outcomes. Citation Format: Samantha R. Jones, Debbynie Barsh, Kathleen McIntyre, Christy J.W. Ledford. Exploring identity-specific stressors among Black women with a family history of cancer [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 B156.

Abstract C062: Racial and ethnic disparities in risk of second primary non-breast cancer in breast cancer survivors

Abstract Purpose: Disparities in cancer outcomes are multifactorial and are attributed to differences in access to care, socioeconomic status, tumor characteristics, treatment, family history, and comorbidity burden. Studies evaluating disparities in breast cancer outcomes have mostly been restricted to Black and White patients. Additionally, whether racial and ethnic disparities affect the risk of second primary cancer in breast cancer survivors, remains under-studied. We evaluated disparities in risk of second primary non-breast cancer in a racially and ethnically diverse cohort of breast cancer survivors treated at an integrated healthcare system. Methods: This retrospective cohort study included 37,222 breast cancer patients (aged ≥18 years) diagnosed between 2008-2020 at Kaiser Permanente Southern California (KPSC). Data on tumor characteristics, cancer treatments and sociodemographic variables were extracted from KPSC’s cancer registry and electronic health records. Patients were followed electronically from breast cancer diagnosis until they developed second primary non-breast cancer, died, disenrolled from the health plan, or reached study’s end (12/31/2021), whichever occurred first. Cox proportional hazards regression was used to report the association [Hazard Ratio (95% Confidence Interval)] between race and ethnicity and second primary non-breast cancer. Results: More than half of the study cohort consisted of non-Hispanic White survivors (51.2%), followed by 20.9% Hispanic survivors, 13.9% Asian/Pacific Islander (API) survivors, 12.7% non-Hispanic Black survivors, and 1.3% survivors of other/mixed races. Overall, 55.7% and 23.9% were diagnosed with local and regional breast cancer, respectively. During a median follow-up of 5.2 years, 4.6% survivors developed second primary non-breast cancers. In the multivariable model adjusted for sociodemographic characteristics, breast tumor characteristics, and breast cancer treatments, Hispanic and API survivors were 25% and 28% less likely to develop second primary cancer compared to White survivors [adjusted HR (95%CI): 0.75 (0.65-0.86)] and 0.72 (0.61-0.86), respectively]. We did not find an increased risk in Black survivors compared to White survivors [adjusted HR (95%CI): 0.91 (0.78-1.04)]. However, factors related to higher risk of second primary non-breast cancers were older age at breast cancer diagnosis, smoking, and higher comorbidity burden. Conclusion: Interestingly, risk of second primary non-breast cancer was lower in Hispanic and API survivors compared to White survivors in this insured cohort. Next steps will include examining which lifestyle factors (e.g. less smoking), or if pharmacological management of modifiable comorbidities might have played a role in the decreased risks seen in these two racial and ethnic groups. Citation Format: Amrita Mukherjee, Zheng Gu, Lie H. Chen, Reina Haque. Racial and ethnic disparities in risk of second primary non-breast cancer in breast cancer survivors [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 C062.

Abstract A151: Examining the influence of health insurance, socioeconomic factors, and rurality on breast cancer screening behaviors in Ohio

Abstract Background: Among Ohio women, breast cancer (BC) is the most common cancer and the second leading cause of cancer death. Inequalities in BC screening are associated with poverty, social injustice, environmental factors, as well as late-state diagnosis, treatment delays, and mortality. The main objective of this study is to examine how BC screening rates differ by rurality and socioeconomic status. Methods: The Ohio State University Comprehensive Cancer Center conducted a population health assessment survey of Ohioans. The Community Initiative Towards Improving Equity and Health Statues (CITIES) project included two waves of data collection 2017-2018 (Wave 1) and 2023-2024 (Wave 2). Participants self-reported various sociodemographic factors (i.e., race, ethnicity, education level, marital status, and insurance coverage), health insurance status, geographic setting, and BC screening adherence. Adherence with BC screening guidelines was defined as having a mammogram every 2 years after age 50. Baseline demographic characteristics were described using counts and percentages stratified by geographic setting. Adherence with BC screening guidelines was summarized with counts and percentages. The relationship between education, marital status[EP1] , insurance status, rurality, and BC screening adherence were assessed with chi-square tests. Results: A total of 300 women were included in this study. Most women (n=210, 70%) resided in urban counties, while 30% (n=90) lived in rural counties. Among rural residents, 96.7% were White, whereas urban residents were 37.6% White, 35.2% African American, 11.9% Hispanic, 9.1% Somali, and 6.2% Asian. Health care coverage was held by 97.8% of rural and 87.6% of urban residents. Over 67.8% of rural residents and over 65.3% of urban residents had at least some post-high school education. Most rural residents (68.7%) were married, compared to 46.7% of urban residents. Among rural residents, 78.9% (n=71) were within mammogram guidelines. Of the women residing in urban areas, 73.8% (n=155) were within mammogram guidelines and 26.2% (n=55) were not. Individuals with health insurance were over 4 times as likely to adhere to BC screening guidelines than those without health insurance (OR: 4.54, p&amp;lt;0.0001). High school graduates were nearly 5 times as likely to adhere to BC screening guidelines compared to those who did not complete high school (OR: 4.88, p&amp;lt;0.0001). White women were twice as likely to be adherent to BC screening guidelines compared to non-White women (OR: 2.07, p=0.007). Marital status (p=0.219) and rurality (p=0.350) were not significantly associated with adherence to BC screening guidelines. Conclusion: Understanding access to cancer care by education, health insurance status, and race, and how these factors influence BC screening is crucial for knowing the challenges that Ohioans may face in BC care. These findings may lead to future development of interventions targeted at population needs, as identified in this study, and improve equity in BC screening access and BC outcomes. Citation Format: Ruvarashe P. Rumano, Chloe M. Hery, Mohamed I Elsaid, Chasity Washington,, Cecilia R. Degraffinreid,, Electra D. Paskett. Examining the influence of health insurance, socioeconomic factors, and rurality on breast cancer screening behaviors in Ohio [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 A151.

Abstract B150: Social determinants of health and comorbidities increasing inflammation cytokines related to breast cancer in African American and Latinx women

Abstract Introduction: Comorbidities such as obesity, Type-2 diabetes (T2D), and hypertension (HTN) are highly prevalent among under-resourced African Americans (AA) and Latinx, and they are associated with breast cancer (BC) risks and outcomes. Social determinants of health (SDOH) also have been found related to BC incidence, stage, and survival. In addition, elevated inflammatory cytokines may be an underlying factor in comorbidities that contribute to tumorigenesis and adverse cancer outcomes. Limited research has been conducted to explore the process and associations among SDOH, comorbidities, and inflammation cytokines related to BC. The purpose of this study was to fill this research gap using a sample recruited from AA and Latinx communities. Methods: This was a cross-sectional study conducted in South LA. A total of 570 AA and Latinx women with or without BC were recruited. A panel of 19 cytokines from serum samples were measured by Luminex assay. Demographic information, body mass index, comorbidities, and diagnosis/stage of BC were collected from patients’ medical records. SDOH factors were selected from the social vulnerability index (e.g., percentage of persons in poverty, unemployed, with no high school diploma) obtained through Geographic Information Systems. Chi-square tests, independent sample Mann-Whitney U tests, and Cox regression were employed to examine the associations between BC diagnosis/stages, comorbidities, and cytokines. Path analyses were adopted to further explore the associations between SDOH, comorbidities, and cytokines. Results: Among the 570 women, 45.79% had a diagnosis of BC. Over half (50.97%) had ER/PR+, HER2-, and 27.80% had triple negative BC. Results from Chi-square tests showed that a higher percentage of women with obesity (p=.001), HTN (p&amp;lt;.0001), and T2D (p=.024) had a BC diagnosis than those without the comorbidity. Women with obesity had significantly higher levels of Leptin, VEGFα, and MIP1b; women with HTN had significantly higher levels of VEGFα and MIP1b; and women with T2D had significantly higher levels of Leptin and TGFβ1/β2. Leptin was found significantly higher in ER/PR+ BC (p&amp;lt;.0001) and VEGFα was significantly higher in triple negative BC (p=.001). Increasing VEGFα and TGFβ1/β2 reduced BC disease-free survival significantly. The path model showed community poverty and education level did not affect TGFβ1/β2 directly but were indirectly associated with them through obesity and T2D status (p&amp;lt;.01). Community poverty level was indirectly associated with the level of MIP1b through HTN status (p&amp;lt;.01). Conclusions: To eliminate breast cancer disparities, effective interventions are needed that account for the social and community contexts in which women live and are treated. Interventions that target comorbidities of T2D, HTN, and obesity are important to reduce the disparities. Citation Format: Weizhou Tang, Yanyuan Wu, Jaydutt Vadgama. Social determinants of health and comorbidities increasing inflammation cytokines related to breast cancer in African American and Latinx women [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 B150.

Abstract C153: Transcriptome-wide study identifies unique pathway functional clusters associated with breast cancer subtypes in population with high indigenous american ancestry

Abstract Purpose: Breast cancer incidence and outcomes differ by US census racial/ethnic category. Since large-scale genetic studies of human disease are predominately focused on populations of European ancestry, little is known about breast cancer molecular biology in Hispanic/Latinos which can widen cancer health disparities due to suboptimal translation of discoveries into clinical practice or public health policy. We aim to identify most relevant pathways in breast cancer subtype differentiation in breast cancer patients from Peru and compared them with those obtained analyzing the Cancer Genome Atlas (TCGA) Breast Cancer (BRCA) dataset and with the published results of the Molecular Profile of Breast Cancer Study (MPBCS), a multi-country Latin American cohort. Patients and Methods: Formalin fixed paraffin embedded tumor tissues samples were whole exome sequenced for a total of 271 patients recruited by the Peruvian Breast Cancer Genomics Study (PEGEN-BC). Quality control was conducted to remove genes with low counts for PEGEN and TCGA-BRCA cohorts, and only female stage II-III breast cancer patients were kept for downstream analysis. Intrinsic tumor subtypes were classified using the estrogen receptor (ER) status-adjusted PAM50 method with genefu package in R. Differential gene expression and pathway analyses between subtypes were performed by the GSEA 4.3.2 software. [LF1] [CX2] Statistical and biological significance was determined using p-values &amp;lt; 0.1 and absolute value of enrichment score &amp;gt; 1.5. Top 20 pathways for each cohort were selected and ranked for comparison. Results: PAM50 classification of the PEGEN-BC cohort defined 20.2% of tumors as Luminal A (LumA), 27.9% as Luminal B (LumB), 27.1% as HER2E, 22.5% as Basal and 2.3% as Normal. Transcriptomic pathway analysis showed that most of the significantly changed pathways were similar to previous findings in the literature, for example, proliferation pathways being upregulated in LumB, HER2E and Basal tumors, compared to the LumA subtype, and a strong dependency on the estrogen pathways for LumA and LumB. Within cohorts, we identified novel clusters of pathways that share related functions. For example, 6 out of the 20 top significant pathways in LumB vs. HER2E comparison for the PEGEN-BC cohort were glycan/glycosylation-related, suggesting the possibility of tumor immune response differences between LumB and HER2E due to glycan related pathway differences among Peruvian patients. Conclusions: We identified novel pathway clusters associated with specific breast cancer subtypes in a population with high Indigenous American ancestry from Peru. Further analyses will be conducted next to explore if the observed patterns were specific to genetic ancestry background or observed independently of genetic ancestry. Citation Format: Chenghuiyun Xu, Valentina A. Zavala, David Rocke, Xiaosong Huang, Sandro Casavilca-Zambrano, Jeannie Navarro-Vásquez, Ruddy Liendo-Picoaga, Monica Calderón, Guillermo Valencia, Patricia Rioja, Carlos A Castañeda, Zaida Morante, Silvia P. Neciosup, Hugo A Fuentes, Julio E. Abugattas, Jose M. Cotrina, Luis A. Salinas, Marco Gálvez-Nino, Jovanny Zabaleta, Andrea S. Llera, Tatiana Vidaurre, Laura Fejerman. Transcriptome-wide study identifies unique pathway functional clusters associated with breast cancer subtypes in population with high indigenous american ancestry [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 C153.

Abstract B117: HT Helper Study: A phone application + patient navigation to improve medication adherence among Latina breast cancer patients experiencing social determinants of health

Abstract Background: Hormone therapy (HT) is highly effective for nearly all breast cancer patients with hormone receptor-positive tumors, which are about 80% of all breast cancer diagnoses. Long-term use of HT reduces cancer recurrence rates and cuts the risk of mortality nearly in half during the second decade after diagnosis. Despite proven benefits, 33% of women who are prescribed HT do not take it as prescribed by their doctor (&amp;lt;80% take their daily dosage). Latina patients are disproportionately affected by Social Determinants of Health (SDoH) that keep them from adhering to HT and are at higher risk of breast cancer recurrence and mortality. Objective: The goal of this 4-year randomized controlled study is to assess the effectiveness of the existing bilingual, culturally tailored, interactive HT Helper App, in combination with patient navigation (PN), on improving adherence to HT among Latina breast cancer patients experiencing SDoH barriers, i.e., income, health insurance, education, health literacy, and language, that impacts their medication adherence. This theory-based intervention will increase patient education, enhance self-efficacy, facilitate communication with the medical team and coordination of resources to address SDoH barriers and help patients develop self-care skills for optimal adherence to HT, ensuring patients the most equitable treatment outcomes possible, including improvement in quality of life, survival, and life expectancy. Study Design. The proposed study involves a parallel 3-group randomized controlled trial with 5-time assessments (baseline, 3, 6, 12, and 18 months) and will enroll 159 breast cancer patients who are prescribed HT and are attending the breast clinic at the Mays Cancer Center at UT Health San Antonio. Intervention components are based on Social Cognitive Theory and elements of Motivational Interviewing. Methods: We will compare the effectiveness of 3 groups on HT adherence: 1) the HT Helper App + PN group vs. the PN alone group vs. the usual care group, and will assess the effect of each study condition on patient self-efficacy to identify side effects, use self-care to manage side effects, and communicate with the medical team. We hypothesize that the HT Helper App + PN and the PN alone groups will have greater rates of HT adherence and higher patient self-efficacy than the usual care group, with the HT Helper App + PN achieving better results than both PN alone and the usual care groups. Conclusion: This proposed multi-level intervention involving a unique combination of mHealth technology + PN has the potential to improve adherence to HT by addressing SDoH and promote equitable breast cancer outcomes, including reduced recurrence and improved quality of life, overall survival and life expectancy among underserved Latina patients. The anticipated outcome is a scalable, evidence-based, and easily disseminated intervention with potentially broad use to patients using oral anticancer medications. Citation Format: Patricia Chalela, Vivian Cortez, Sandra Sivak, Armida Flores, Martha De La Mora, Zully Garcia, Byeongyeob Choi, Edgar Muñoz, Qurathul Ahmed, Audrey Cordova, Maria I Sung-Cuadrado, Asra Aslam, Cliff Despres, Alyssa Gonzales, Virginia G Kaklamani, Kate I. Lathrop, Marcela Mazo Canola, Devasena Inupakutika, David Akopian, Amelie G. Ramirez. HT Helper Study: A phone application + patient navigation to improve medication adherence among Latina breast cancer patients experiencing social determinants of health [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 B117.

Abstract A055: Neighborhood Deprivation and Oncotype DX Recurrence Scores among Black and White Women: the interplay between race, place, and tumor biology

Abstract Background: Breast cancer (BC) mortality disparities have persisted between non-Hispanic Black (NHB) and non-Hispanic White (NHW) women, even those diagnosed with prognostically favorable BC. The Oncotype Dx Recurrence score (ODX) test is a gene expression panel that can be used to identify estrogen receptor (ER)-positive BC with aggressive tumor biology. Previous studies have found that Black women are more likely to have higher ODX scores than White women and socioeconomic factors (e.g., area-level income, urbanicity) are associated with higher ODX scores. We explored race-stratified associations of neighborhood deprivation and ODX to help elucidate the interplay between race, place, and tumor biology. Methods: Neighborhood deprivation was examined in relation to ODX scores among 7,100 NHB and NHW women diagnosed with ER-positive BC (stage I–IIIA and ≤3 lymph nodes) between 2010–2017, followed through 2022, and identified by the Georgia Cancer Registry. The neighborhood deprivation index (NDI) was used to characterize neighborhood deprivation. Principal component analysis of block group-level American Community Survey data representing six domains (poverty, income, occupation, housing, employment, and education) was used to derive the NDI composite score. NDI was assessed in quartiles and linked to patient residence at the time of diagnosis. Three cut-points were used for ODX scores (low &amp;lt;18, intermediate 18–30, high ≥31). Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated to determine the prevalence of ODX scores based on NDI by race/ethnicity. Results: This study included 1651 NHB and 5449 NHW women. There were 4152 (58.5%) with a low ODX Score and 514 (7.2%) with a high ODX score; 2773 (39.1%) resided in the least deprived neighborhoods (NDI quartile 1) and 928 (13.1%) resided in the most deprived neighborhood (NDI quartile 4). Living in the most deprived neighborhood was associated with an increased prevalence of high ODX scores in models adjusted for age, race, and stage (PR=1.23, 95% CI 0.97–1.62). Stratification by race showed associations were stronger among NHW women (PR=1.41, 95% CI 1.02–1.95) but null among NHB women (PR= 0.91, 95% CI 0.59-1.39). Overall, NHB women were more likely to have a high ODX compared to NHW women. The highest prevalence of a high ODX was observed among NHB women living in the least deprived neighborhoods (PR=1.92, 95% CI 1.34–2.77). Conclusions: Findings from this study suggest that living in a deprived neighborhood increases the prevalence of high ODX among NHW women but not NHB women. NHB women in the least deprived neighborhoods had the greatest prevalence of high ODX scores. The intersection between race, neighborhood, and tumor biology needs more nuanced investigation of the social-structural drivers of disparate BC outcomes. Citation Format: Jasmine M. Miller-Kleinhenz, Lauren E. Barber, Lindsay J. Collin, Maret L. Maliniak, Demetria J. Smith-Graziani, Lauren E. McCollough. Neighborhood Deprivation and Oncotype DX Recurrence Scores among Black and White Women: the interplay between race, place, and tumor biology [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 A055.

Abstract A111: Leveraging African American women as change agents to reduce obesity-related breast cancer risk: An evaluation of a network-based pilot intervention promoting the Mediterranean diet

Abstract BACKGROUND: Obesity is a key risk factor for breast cancer (BC) incidence, recurrence, and mortality among post-menopausal African American (AA) women. Many older AA women are likely to report fewer healthy dietary behaviors, and those who are overweight or obese are likely to share similar dietary patterns as their social networks (SNs). AA women are also likely to receive information on BC risk from their SNs. Thus, AA women who share information on healthy dietary behaviors are well-positioned to become change agents toward reducing obesity and improving BC outcomes among their SNs. This presents a novel opportunity to increase the impact of evidence-based (EB) interventions focused on reducing obesity-related BC risk. This study aimed to assess the effects of the MedDiet-SN pilot intervention among participants trained as change agents to improve obesity-related BC risk reduction behaviors for themselves and their SNs through EB information sharing. Methods: MedDiet-SN was a 10-week, pre-/post- pilot intervention promoting the uptake of the Mediterranean diet, with participant training on effective EB information sharing. A community-based participant advisory board informed the pilot. Study procedures were IRB approved. Eligible participants were AA women, ≥60 years old, overweight or obese, Chicago area residents, and with no severe health conditions. Sixteen women participated, and 30 of their SN members (age ≥18 years) were recruited through participant referral. Predictors included time from pre- to post-study and session dosage for participants, and participant EB information sharing on healthy eating for SN members. Outcomes for both groups included BC and diet knowledge, dietary change attitudes (motivation, self-efficacy), dietary behavior change, and BMI. EB information sharing on healthy eating was an additional outcome for participants. Bivariate and multivariate analyses were performed to assess outcomes. Results: In crude and adjusted time models, participants showed improved knowledge, behavior change, BMI, and EB information sharing (p&amp;lt;0.05). In adjusted dosage models, participants showed improved knowledge, attitudes, and EB information sharing (p&amp;lt;0.05). SN members showed improved attitudes and behavior change based on participant EB information sharing on healthy eating (p&amp;lt;0.05). In addition, there was a high concordance between participant EB information sharing and SN EB information learned (&amp;gt;70%). CONCLUSION: This research is innovative in that it 1) shows the effectiveness of a network-based intervention promoting healthy dietary behaviors for obesity-related BC risk reduction among AA women, 2) supports the value of scaling up interventions by leveraging participants as change agents for EB information sharing among SNs, and 3) provides a contribution to emerging research on positive intervention spillover effects to SNs. It is anticipated that results from this study will inform the development of future network-based interventions that aim to reduce obesity-related BC risk and improve health outcomes for AA women. Citation Format: Nyahne Bergeron, Mona Strahan, Patricia Hardmon, Marja Stanford- Leak, Anita Stevens, Annie Young, Devyanne Ward, Lois White, Eunhye Lee, Lisa Tussing-Humphreys, Marian Fitzgibbon, Yamilé Molina. Leveraging African American women as change agents to reduce obesity-related breast cancer risk: An evaluation of a network-based pilot intervention promoting the Mediterranean diet [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 A111.

See Me, Hear Me: Racial Discrimination Among Women Seeking Breast Cancer Care.

Discrimination can contribute to worse health outcomes, but its prevalence in breast cancer is not well studied. We aimed to understand how women with stage I-III breast cancer faced discrimination in health care and everyday settings through a cross-sectional survey. 296 women, 178 (60%) Non-Hispanic White (NHW), 76 (26%) Non-Hispanic Black (NHB), and 42 (14%) Hispanic participated. NHB women reported significantly more discrimination in everyday life compared to NHW women (score 20.1 vs 16.1, p<.001) and Hispanic women (score 20.1 vs 16.0, p<.001). In the health care setting, NHB had statistically more frequent reports of being ignored (23.7% vs. 5.6%), treated with less respect (21.1% vs. 7.3%), and treated with less courtesy (18.7% vs. 6.2%; all P=<.001) when compared to NHW women. NHB women experience a higher degree of discrimination both inside and outside of health care. Further research to understand discrimination on breast cancer outcomes is warranted.

Trajectories in mammographic breast screening participation in middle-age overweight and obese women: A retrospective cohort study using linked data

ObjectivesDespite the established benefits and availability of mammographic breast screening, participation rates remain suboptimal. Women with higher BMIs may not screen regularly, despite being at increased risk of postmenopausal breast cancer and worse outcomes. This study investigated the association between prospective changes in BMI and longitudinal adherence to mammographic screening among women with overweight or obesity. MethodsRetrospective cohort study of women (N = 2822) participating in the Australian Longitudinal Study on Women's Health with an average follow-up of 20 years, with screening participation enumerated via BreastScreen NSW, Australia clinical records over the period 1996–2016. Association between BMI and subsequent adherence to screening was investigated in a series of marginal structural models, incorporating a time variant/invariant socio-demographic, clinical, and health behaviour confounders. Models were also stratified by a proxy measure of socio-economic status (education). ResultsParticipants with overweight/obesity were less adherent to mammography screening, compared to healthy/underweight participants (OR=1.29, 95 % CI=1.07, 1.55). The association between overweight/obesity and non-adherence was higher among those who ever had private health insurance (OR=1.30, 95 % CI=1.05, 1.61) compared to those who never had private health insurance and among those with lower educational background (OR=1.38, 95 % CI=1.08, 1.75) compared to those with higher educational background. ConclusionsLong-term impacts on screening participation exist among women with higher BMI, who are less likely to participate in routinely organised breast screening. Women with a higher BMI should be a focus of efforts to improve breast screening participation, particularly given their increased risk of breast cancer and association of higher BMI with worse breast cancer outcomes among older women.

Meaningful engagement of people living with cancer: Leveraging breast cancer survivors in a stigma reduction intervention in Tanzania.

Cancer-related stigma is a key driver of advanced breast cancer stage in Sub-Saharan Africa (SSA). We developed and tested the impact of a breast cancer survivor-led Stigma reduction intervention (SRI) on stigma and treatment adherence of newly diagnosed patients with breast cancer in Tanzania. Breast cancer survivors were trained on breast cancer knowledge and motivational interviewing. A total of 4 trained survivors delivered a SRI (standardized flipchart breast education talk, personal testimony, and motivational interviewing) to 30 newly diagnosed patients with breast cancer before treatment. Pre- and post-intervention knowledge surveys and stigma scale surveys were analyzed via Fisher's exact test and Wilcoxon rank-sum tests. A discussion was held with a group of survivors after the intervention period to elicit feedback on their intervention experience. Among the 30 patients, breast cancer knowledge (median overall percent correct) increased from 28% (IQR: 18%-45%) to 85% (IQR: 79%-88%) (p<0.001) and stigma (median score) decreased from 75 (IQR: 57-81) to 53 (IQR: 44-66) (p<0.01) following the intervention. All participants were willing to pursue hospital-based treatment after undergoing the intervention. Eighty-seven percent (n=26) initiated treatment at 8-week follow-up after the intervention. All survivors endorsed feeling empowered and valued in their role in this intervention. Breast cancer survivors are a powerful group to combat the lack of knowledge and stigma in community and healthcare settings. Expanding the scope and scale of this intervention holds promise for improving treatment-seeking behavior and ultimately breast cancer outcomes in SSA.

The relationship between tumor budding and survival of patients with breast cancer: A meta-analysis.

Tumor budding has been proposed as a potential prognostic marker in various cancers, but its association with survival outcomes in breast cancer (BC) remains unclear. This meta-analysis aimed to clarify the relationship between tumor budding and survival outcomes in patients with BC. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science. Cohort studies examining the association between tumor budding and overall survival (OS) and progression-free survival (PFS) in BC patients were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for potential heterogeneity. Eleven cohort studies, including 2,828 patients, met the inclusion criteria. High tumor budding was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.37-2.60, P < 0.001) and PFS (HR = 1.89, 95% CI = 1.32-2.71, P < 0.001). Subgroup analyses revealed a stronger association in studies where high tumor budding was defined as ≥ 10 buds / high-power field (HPF) compared to those with lower cutoffs. Sensitivity analyses confirmed the robustness of the findings. This meta-analysis demonstrates that high tumor budding is associated with significantly worse OS and PFS in BC patients, underscoring its prognostic significance. These findings suggest tumor budding could be a valuable marker in clinical assessments, and further research is needed to standardize its evaluation criteria in BC.

Estrogen receptors and extracellular matrix: the critical interplay in cancer development and progression.

Cancer remains a significant global health concern. Breast cancer is a multifaceted and prevalent disease influenced by several factors, among which estrogen receptors (ERs) and the extracellular matrix (ECM) play pivotal roles. ERs, encompassing ERα and ERβ, exert significant diversity on tumor behavior, cell signaling, invasion, and metastatic potential, thus guiding breast cancer prognosis. Understanding the multifunctional connections between ERs and ECM that mediate the dynamics of tumor microenvironment is vital for unraveling the complexity of breast cancer pathobiology and identifying novel therapeutic targets. This critical review delves into the intricate nature of ERs, emphasizing their structural isoforms and the consequential impact on breast cancer outcomes. A detailed examination of ER-mediated cell signaling pathways reveals how differential expression of ERα and ERβ isoforms influence breast cancer cell behavior. The functional ERs-matrix interactions emerge as a pivotal factor in modulating epigenetic mechanisms of breast cancer cells, orchestrating changes in cellular phenotype and expression patterns of matrix modulators. Specifically, ERα isoforms are shown to regulate ECM signaling cascades, while the effects of ECM components on ERα activity highlight a bidirectional regulatory axis. The diversity of ERβ isoforms is also highlighted, illustrating their distinct contribution to ECM-mediated cellular responses. This review underscores the complex interplay between ERα/β isoforms and the ECM, shedding light onto the potential therapeutic strategies targeting these interactions to improve breast cancer management.