Higher Breast Cancer Mortality Research Articles

Young Black Women's Breast Cancer Knowledge and Beliefs: A Sequential Explanatory Mixed MethodsStudy.

Black women under the age of 50 have a 111% higher breast cancer mortality rate than their White counterparts. The breast cancer mortality disparities among young Black women may be due in part to the fact that they are more likely to be diagnosed with late-stage, invasive breast cancer tumors. Psychosocial factors, such as lack of perceived risk for breast cancer, lack of awareness of breast cancer risk factors, and ambiguity about breast cancer screening guidelines are areas that are under investigated among young Black women. The purpose of this study was to identify young Black women's cancer beliefs and level of breast cancer risk knowledge. A sequential explanatory mixed methods study was conducted using quantitative data from the Health Information Trends Survey 6 (HINTS 6) (n = 25) and qualitative data from interviews with young Black female college students (n = 13). The results of the quantitative data analysis were used to guide the development of the qualitative interview guide. Data regarding participants' cancer beliefs, cancer risk factor knowledge, perceived cancer risk, and ambiguity about cancer screening behaviors were analyzed. The findings indicated young Black women have low perceived risk of developing cancer. Most participants were not aware of cancer recommendations that were targeted towards women under the age of 40. In addition, knowledge about lifestyle behavior risk factors for breast cancer was relatively low. Our findings underscore the importance of developing, disseminating, and implementing breast cancer education interventions that are targeted towards young Black women.

Abstract A071: County-level racial and ethnic diversity index and cancer mortality in the U.S.

Abstract Background: The United States is experiencing a demographic trend of increasing racial and ethnic diversity. While persistent racial and ethnic disparities in cancer mortality are well documented, little is known about the impact of racial and ethnic diversity on cancer outcomes in the United States. Purpose: We examined associations between the U.S. county-level racial & ethnic diversity index and age-adjusted cancer mortality rates. We also assessed whether associations differed by geographic region, persistent poverty, and rurality. Methods: We used the U.S. Census Bureau’s 2020 Racial and Ethnic Diversity Index, which estimates the chance that two people chosen at random will be from different racial and ethnic groups. The diversity index was calculated at the county-level and categorized as follows: less than 35% (lowest), 35.0 to 44.9%, 45.0 to 54.9%, 55.0 to 64.9% and 65.0% or more (highest). We described county- level sociodemographic characteristics according to the diversity index categories. We calculated mean and standard errors of the county-level age-adjusted cancer mortality rates per 100,000 from 2016-2020 (overall and by site for the top four sites for cancer mortality) across the diversity index categories. We used multivariable linear regression models to examine associations between racial and ethnic diversity and cancer mortality, overall and by cancer site. We also assessed models stratified by geographic region (U.S. Census regions), persistent poverty and rurality. Results: Counties with more racial and ethnic diversity had a younger median age, a higher proportion of college graduates, and were less likely to be rural. Cancer mortality rates per 100,000 were lower in the most vs. least diverse counties, overall (144.7 vs. 164.6), and for lung (32.5 vs. 44.8), and colorectal cancer (13.0 vs. 15.6). In adjusted models, the highest vs. lowest racial and ethnic diversity was associated with a 7.25 decrease in overall cancer mortality rates (95% CI: -10.5 to -4.0), a 6.55 decrease in lung cancer mortality (95% CI: -8.0 to -5.1) and a 1.49 increase in breast cancer mortality (95% CI: 0.7 to 2.3). The diversity index was not associated with colorectal cancer mortality or pancreatic cancer mortality in adjusted models. Inverse associations of diversity index and overall cancer mortality were strongest in the South Census region (b=-13.0, 95% CI: -17.5 to -8.4), in non-persistent poverty counties (b=-9.0, 95% CI: -12.4 to -5.5), and in rural counties (b=-8.6, 95% CI: -13.2 to -4.1). Conclusions: Greater racial and ethnic diversity was associated with lower overall cancer mortality and lung cancer mortality rates, although it was associated with significantly higher breast cancer mortality rates. Findings help elucidate whether and how social factors may differentially impact subgroups of the population to influence cancer mortality. This study addresses an urgent need to explore contextual factors that may shape racial and ethnic disparities at the population level. Citation Format: Kelly A. Hirko, Breanna Greteman, Sabrina Ford, Sarah H. Nash. County-level racial and ethnic diversity index and cancer mortality in the U.S. [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 A071.

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 A154: Mammograms Across Missouri: A Qualitative Evaluation among Healthcare Providers to Improve Breast Cancer Screening in Rural Communities

Abstract Introduction: Breast cancer is the leading cause of cancer-related deaths among women, with rural communities having the highest rates of breast cancer mortality. Despite this burden, many women begin mammography later than recommended and the mammography screening rate remains low, with a previously reported declining trend, particularly among rural women compared to urban women. This study seeks to identify barriers to breast cancer screening and examine strategies to overcome these barriers in rural Missouri. Methods: In partnership with the Missouri Cancer Consortium and the Missouri Comprehensive Cancer Control Programs, we conducted key informant interviews with mammography health providers at health centers in each of ten counties with the highest breast cancer mortality and lowest screening mammography rates in Missouri. Semi-structured interviews included questions about seeking and delivering breast cancer screening as well as provider experiences with patient navigation, mobile mammography, and the CDC’s National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Data were analyzed using a deductive-inductive thematic approach in NVivo 14. Results: We conducted 14 interviews with health providers across 12 health sites. The majority of these sites used patient navigation (67%), mobile mammography (80%), and the CDC NBCCEDP (67%) as strategies to improve access to breast healthcare. Health providers frequently mentioned “no-shows” as a major challenge to providing breast healthcare, along with limited transportation, cost, fear, and competing work priorities as the major barriers faced by patients in seeking breast healthcare. Patient navigation and mobile mammography were beneficial in bringing breast healthcare closer to the community, while the CDC NBCCEDP covered screening and follow-up costs. The main facilitating factors to implementing these strategies were having dedicated staff and funding for patient navigation, and existing partnerships with other health institutions for mobile mammography. However, health providers identified several implementing challenges for the strategies. This included limited staff capacity and difficulty contacting or following up patients to schedule appointments for patient navigation and mobile mammography. For the CDC NBCCEDP, the challenges included difficulty identifying eligible patients and extensive paperwork in the enrollment process. Providers recommended increasing staff capacity to support patient navigation, using digital technology in identifying and enrolling women for the CDC NBCCEDP, and integrating mobile mammography with the CDC NBCCEDP to improve implementation efficiency. Discussion: The integration of multiple component strategies within breast healthcare may address the multi-level barriers women face in accessing breast cancer screening. This study contributes to the identification of organizational supports and informs development of policies needed to enhance the adoption and implementation of strategies that support the effective delivery of breast healthcare. Citation Format: Thembekile Shato, Carmen Vardeman, Sarah J. Chavez, Ashley C. Holmes, Joann Lee, Xarria Lewis, Katie Manga, Misty Phillips, Keisha Windham, Bettina F. Drake. Mammograms Across Missouri: A Qualitative Evaluation among Healthcare Providers to Improve Breast Cancer Screening in Rural Communities [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 A154.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry.

Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n=20) and WW (n=20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.

Exposure to Pesticides and Breast Cancer in an Agricultural Region in Brazil.

Rural workers are disproportionally exposed to pesticides and might be at an increased risk of developing chronic diseases. Here, we investigated the impact of pesticide exposure on breast cancer (BC) risk and disease profile in rural female workers. This is a case-control study that prospectively included 758 individuals. The study was conducted in the Southwest region of Paraná state in Brazil, a region characterized by family-based agriculture and intensive use of pesticides. We found that this region has a 41% higher BC diagnosis rate and 14% higher BC mortality rate than the mean rates in Brazil, as well as a pesticide trade volume about 6 times higher than the national average. We showed substantial exposure in this population and found that even women who did not work in the fields but performed equipment decontamination and clothes washing of male partners who worked in the fields had urine samples positive for glyphosate, atrazine, and/or 2,4-D. The crude association showed a significantly higher risk of BC among women exposed to pesticides (OR: 1.58, 95% CI 1.18-2.13). Adjusted analyses showed a lower and nonstatistically significant association (OR: 1.30, 95% CI 41 0.87-1.95). Stratification on disease profile showed a significantly higher risk of lymph node metastasis (adjusted OR: 2.19, 95% CI 1.31-3.72) in women exposed to pesticides. Our findings suggest that female populations exposed to pesticides are at a higher risk of developing BC with a more aggressive profile and draw attention to the need to monitor rural populations potentially exposed to pesticides in the field or at home.

Multiplicity of benign breast disease lesions and breast cancer risk in African American women.

The risk of developing subsequent breast cancer is higher in women diagnosed with benign breast disease (BBD) but these studies were primarily performed in non-Hispanic white populations. Still, these estimates have been used to inform breast cancer risk models that are being used clinically across all racial and ethnic groups. Given the high breast cancer mortality rates among African American (AA) women, it is critical to study BBD in this population, to ensure the risk models that include this information perform adequately. This study utilized data from AA women who underwent benign breast biopsies at a hospital served by the University Pathology Group in Detroit, Michigan, from 1998 to 2010. Patients were followed for subsequent breast cancers through the population-based Metropolitan Detroit Cancer Surveillance System (MDCSS). BBD lesion scores were assigned to represent the severity or extent of benign breast lesions, with higher scores indicating a greater number of distinct lesion types. Of 3,461 eligible AA women with BBD in the cohort, 6.88% (n=238) subsequently developed breast cancer. Examined individually, six of the eleven lesions (apocrine metaplasia, ductal hyperplasia, lobular hyperplasia, intraductal papilloma, sclerosing adenosis, columnar alterations and radial scars) were significantly associated with increased risk of breast cancer after adjustment for age and year of biopsy and were further considered in multiple lesion models. For every different type of benign breast lesion, subsequent risk of breast cancer increased by 25% (RR=1.25, 95% CI: 1.10, 1.42) after adjustment for age at biopsy and proliferative versus non-proliferative disease. In summary, this study affirms the increased breast cancer risk in AA women with BBD, particularly in those with multiple lesions. These findings have implications for the management of breast cancer risk in millions of women affected by BBD, a high risk group that could benefit from personalized surveillance and risk reduction strategies.

Breast Cancer Knowledge Among Amish and Mennonite Women.

Breast cancer is the most common cancer diagnosis for women in the USA and ranks second in cancer-related deaths. Disproportionately higher breast cancer rates can be found in rural and Appalachian regions due to several social drivers of health, including poverty, access to healthcare, and lack of culturally sensitive health education. Amish and Mennonite communities, religious groups with distinct cultural practices and beliefs, experience lower mammography screening and higher breast cancer mortality rates (among Amish women). This study focuses on knowledge about breast cancer and causes of cancer among Amish and Mennonite women. A total of 473 women participated in the study at 26 separate women's health clinics throughout Ohio, consisting of 348 Amish and 121 Mennonite women, the largest study conducted on breast cancer knowledge spanning dozens of communities. Statistically significant differences were found in total knowledge scores between Amish and Mennonite women (rpb = .178, n = 466, p = .007), with Amish women having lower scores and stronger beliefs in myths associated with breast cancer cause and symptoms (χ(1) = 7.558, p = .006). Both groups often provided scientifically accurate descriptions of cancer etiology. The majority of participants underestimated breast cancer risk, highlighting the need for culturally appropriate health education programs that consider numeracy and health literacy. By implementing targeted interventions and fostering partnerships with community stakeholders using a multifaceted approach that incorporates cultural sensitivity, community engagement, and collaboration, significant progress can be made towards reducing breast cancer disparities and improving health outcomes.

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p=.03), 53% more deaths after breast cancer (p<.001), and 44% higher breast cancer mortality (p=.03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p<.001), more total breast cancers (p<.001), and more deaths after breast cancer (p<.001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p<.001). MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Abstract PO3-10-11: Mujeres Avanzando a la Sobrevida (MAS: women going forward in survival): Breast Cancer Characteristics and Delays in Care in Honduras

Abstract Introduction: Low and middle-income countries have exceedingly high breast cancer mortality rates primarily due to delays to diagnosis and treatment. The Breast Health Global Initiative (BHGI) recommends a diagnostic interval (time from initial provider visit to receiving a diagnosis) of &amp;lt; 60 days. Honduras is one of the poorest countries in the western hemisphere and has a paucity of published breast cancer research. Our objective was to understand delays in breast cancer diagnosis and treatment in Honduras. Methods: We initiated a prospective cohort study (Mujeres Avanzando a la Sobrevida (MAS: Women Going Forward in Survival)) in 2021 at two hospitals in two major cities in Honduras. All patients with newly diagnosed breast cancer were invited to participate. We prospectively collected demographic, cancer, and treatment data through patient interviews and surveys. We also determined several time intervals including: onset of symptoms to initial provider visit (patient interval), initial provider visit to biopsy (diagnostic interval), and biopsy to first treatment (treatment interval). Patients also completed the Unger-Saldana Delay Survey to assess their perceptions of any delays in cancer care and reasons for these delays. Results: We enrolled 95 patients with an average age of 54 years. 73% of patients reported an income of &amp;lt; 1 minimum wage (&amp;lt; 8,448 lempiras/month). 93% were housewives, and 35% were married. The majority of patients had an elementary school education or no education (61%). The most common first symptom was a breast lump (81%). The majority of patients had advanced stage disease (Stage III and IV: 64%). The mean patient interval was 185 days. The mean diagnostic interval was 153 days, and the mean treatment interval was 139 days. Most patients (61%) thought their symptoms were slightly serious or not serious at all, and 78% did not think their symptoms were due to cancer. Most patients (60%) thought they were able to see a physician immediately or soon after symptoms developed (63%). Patient stated reasons for not seeking care earlier included believing their symptoms would self-improve, being unsure which health service to go to, lack of money, and fear. Similarly, most patients (67%) thought the time between seeing their first provider and visiting the cancer hospital was immediate or soon but not immediately. Reasons for this delay included lack of information, lack of money, wait times to appointment or tests, incorrect initial diagnosis, and fear. Conclusion: In this prospective cohort study, nearly two-thirds of patients in Honduras were diagnosed with stage III/IV breast cancer. We found marked delays in patient, diagnostic, and treatment intervals, even though patients perceived their care to be immediate. Importantly, the diagnostic interval far exceeded 60 days, as recommended by the BHGI. This study provides initial insight into delays in breast cancer care in Honduras and provides an opportunity to target obstacles to early diagnosis and treatment and to improve breast cancer survival. Citation Format: Saranya Prathibha, Alejandra Molina, Jorge Siryi, Kristhel Gaitán, Mildred Raudales, Manuel Maldonado, Todd Tuttle, Suyapa Bejarano. Mujeres Avanzando a la Sobrevida (MAS: women going forward in survival): Breast Cancer Characteristics and Delays in Care in Honduras [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-11.

The VEGF-Hypoxia Signature Is Upregulated in Basal-like Breast Tumors from Women of African Ancestry and Associated with Poor Outcomes in Breast Cancer.

Black women experience the highest breast cancer mortality rate compared with women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry. We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n = 182) and the University of Chicago (Chicago, IL; n = 161). We also analyzed RNA sequencing data from Nigeria (n = 84) and The Cancer Genome Atlas (TCGA) datasets (n = 863). Patient prognosis was analyzed using multiple datasets. The VEGF-hypoxia signature was highest in the basal-like subtype compared with other subtypes, with greater expression in Black women compared with White women. In TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared with non-necrosis tumors (P < 0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation, and necrosis. T-cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in TCGA dataset. Finally, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (P < 0.0001) and SCAN-B datasets (P = 0.002). These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora.

Abstract 6116: Rs2363956, a coding variant of ANKLE1, drives triple-negative breast cancer disparity by altering DNA damage response

Abstract African American women have a 42% higher breast cancer mortality rate than European American women and are over twice as likely to develop triple-negative breast cancer (TNBC). We have previously demonstrated that this higher incidence of TNBC is tied to ancestry-related biological determinants of TNBC tumor biology, including possible novel genetic drivers that may result in reduced treatment efficacy. Within the TCGA BRCA cohort, we have previously found that high ANKLE1 gene expression significantly improves survival in European Americans but not in African Americans. This difference may be attributed to the presence of a polymorphic variant of ANKLE1, rs2363956. The minor G allele of rs2363956 leads to a structural alteration in ANKLE1, potentially changing its functionality. Interestingly, among our International Center for the Study of Breast Cancer Subtypes (ICSBCS) patient cohort, we observed that 41-53% of European Americans with TNBC were homozygous for the G allele as compared to only ~14% of African American patients. These observations suggest that the presence of the rs2363956 polymorphic variant may drive differences between European American and African American patients. ANKLE1 is a conserved gene among eukaryotic organisms and has been reported as an endonuclease implicated in DNA damage repair. Among our patient cohort (n=62) we have observed that patients homozygous for the G allele (n=13) are enriched for COSMIC mutational signatures 2 and 13 (P≤.05 and P≤.001, respectively), that denote overactivity of APOBEC deaminases, as compared to patients homozygous for the T allele (n=19). Therefore, the increased mutational burden present in those patients caused by APOBEC overactivity may sensitize those cancer cells to chemotherapeutics or other therapies. Alternatively, the patients homozygous for the T allele may have an increased capacity for DNA damage repair that does not involve APOBEC activity. Using the MDA-MB-231 cell line, which is homozygous for the T allele, we performed an ANKLE1 knockdown with siRNA in order to examine the impact of ANKLE1 loss on DNA damage repair. Upon treatment with 25 μM, 10 μM, and 5 μM of Cisplatin we observe increased γ-H2AX and cell shrinkage in the ANKLE1 knockdowns as compared to cells treated with control siRNA, denoting increased DNA damage and apoptosis. Additionally, after knocking down ANKLE1 we observed decreased proliferation. Based on these observations, ANKLE1 is critical for DNA damage response in TNBC cells and may be implicated in the genomic stability of TNBC. The polymorphic variants observed may impact this function and in part explain why European American patients have improved survival, as compared to African American patients. Citation Format: Yanira Guerra, Rachel Martini, Olivier Elemento, Melissa B. Davis. Rs2363956, a coding variant of ANKLE1, drives triple-negative breast cancer disparity by altering DNA damage response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6116.

Income Segregation, Conditional Cash Transfers, and Breast Cancer Mortality Among Women in Brazil

Women living in income-segregated areas are less likely to receive adequate breast cancer care and access community resources, which may heighten breast cancer mortality risk. To investigate the association between income segregation and breast cancer mortality and whether this association is attenuated by receipt of the Bolsa Família program (BFP), the world's largest conditional cash-transfer program. This cohort study was conducted using data from the 100 Million Brazilian Cohort, which were linked with nationwide mortality registries (2004-2015). Data were analyzed from December 2021 to June 2023. Study participants were women aged 18 to 100 years. Women's income segregation (high, medium, or low) at the municipality level was obtained using income data from the 2010 Brazilian census and assessed using dissimilarity index values in tertiles (low [0.01-0.25], medium [0.26-0.32], and high [0.33-0.73]). The main outcome was breast cancer mortality. Mortality rate ratios (MRRs) for the association of segregation with breast cancer deaths were estimated using Poisson regression adjusted for age, race, education, municipality area size, population density, area of residence (rural or urban), and year of enrollment. Multiplicative interactions of segregation and BFP receipt (yes or no) in the association with mortality (2004-2015) were assessed. Data on 21 680 930 women (mean [SD] age, 36.1 [15.3] years) were analyzed. Breast cancer mortality was greater among women living in municipalities with high (adjusted MRR [aMRR], 1.18; 95% CI, 1.13-1.24) and medium (aMRR, 1.08; 95% CI, 1.03-1.12) compared with low segregation. Women who did not receive BFP had higher breast cancer mortality than BFP recipients (aMRR, 1.17; 95% CI, 1.12-1.22). By BFP strata, women who did not receive BFP and lived in municipalities with high income segregation had a 24% greater risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.24: 95% CI, 1.14-1.34); women who received BFP and were living in areas with high income segregation had a 13% higher risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.13; 95% CI, 1.07-1.19; P for interaction = .008). Stratified by the amount of time receiving the benefit, segregation (high vs low) was associated with an increase in mortality risk for women receiving BFP for less time but not for those receiving it for more time (<4 years: aMRR, 1.16; 95% CI, 1.07-1.27; 4-11 years: aMRR, 1.09; 95% CI, 1.00-1.17; P for interaction <.001). These findings suggest that place-based inequities in breast cancer mortality associated with income segregation may be mitigated with BFP receipt, possibly via improved income and access to preventive cancer care services among women, which may be associated with early detection and treatment and ultimately reduced mortality.

Late-stage diagnosis: The driving force behind high breast cancer mortality in Ethiopia: A systematic review and meta-analysis.

Breast cancer continues to be the most common malignancy and the leading cause of cancer-related deaths in Ethiopia. The poor prognosis and high mortality rate of breast cancer patients in the country are largely caused by late-stage diagnosis. Hence, understanding the epidemiology of late-stage diagnosis is essential to address this important problem. However, previous reports in Ethiopia indicated inconsistent findings. Therefore, this literature review was conducted to generate dependable evidence by summarizing the prevalence and determinants of late-stage diagnosis among breast cancer patients in Ethiopia. Pertinent articles were retrieved by systematically searching on major electronic databases and gray literature. Data were extracted into an Excel spreadsheet and analyzed using the STATA 17 statistical software. The pooled estimates were summarized using the random effect meta-analysis model. Heterogeneity and small study effect were evaluated using the I2 statistics and Egger's regression test in conjunction with the funnel plot, respectively. Meta-regression, sub-group analysis, and sensitivity analysis were also employed. Protocol registration number: CRD42024496237. The pooled prevalence of late-stage diagnosis after combining reports of 24 studies with 8,677 participants was 65.85 (95% CI: 58.38, 73.32). Residence (adjusted OR: 1.92; 95% CI: 1.45, 2.53), patient delay at their first presentation (adjusted OR: 2.65; 95% CI: 1.56, 4.49), traditional medicine use (adjusted OR: 2.54; 95% CI: 1.89, 3.41), and breast self-examination practice (adjusted OR: 0.28; 95% CI: 0.09, 0.88) were significant determinants of late-stage diagnosis. Two-thirds of breast cancer patients in Ethiopia were diagnosed at an advanced stage. Residence, delay in the first presentation, traditional medicine use, and breast self-examination practice were significantly associated with late-stage diagnosis. Public education about breast cancer and its early detection techniques is crucial to reduce mortality and improve the survival of patients. Besides, improving access to cancer screening services is useful to tackle the disease at its curable stages.

Breast cancer mortality among ultra-orthodox and non-ultra-orthodox Israeli women: A retrospective cohort study

BackgroundBreast cancer is the leading cause of cancer death in Israeli women. Previous studies found socioeconomic status and other risk factors impact breast cancer outcomes. The ultra-orthodox community is characterized by a longer life expectancy, lower rates of mammography performance, higher fertility rates and other sociodemographic variables that may be related to breast cancer mortality. This study examined disparities in breast cancer mortality between ultra-Orthodox and non-ultra-Orthodox Israeli women. MethodsThis retrospective cohort study for breast cancer mortality included the all Jewish Israeli citizens women born between 1940 and 1960 and lived in communities with over 20,000 residents (n = 628,617). Data was collected from various sources, monitoring a period of 31 years; for each participants, their sociodemographic characteristics were compiled from the population registry, the tax authority, the education registry, and the Central Bureau of Statistics (CBS). Variables included religiosity, age, marital status, children, origin, education, and income. Multivariable Cox models evaluated predictors of mortality. ResultsOf the 628,617 women in the study, 29,611 were ultra-Orthodox. Ultra-Orthodox women had higher marriage rates, more children, and lower secular education and income. Mortality was 108.8/100,000 overall, lower among ultra-Orthodox (83.4/100,000) than non-ultra-Orthodox women (110.1/100,000) despite their risk factors. Using a multivariate model to evaluate the association between ultra-Orthodoxy and breast cancer mortality, the study found higher breast cancer mortality rate among non-ultra-Orthodox women compared to ultra-Orthodox women (HR = 1.491; 99% CI = 1.232, 1.804). Associations with sociodemographic variables were different for each group. ConclusionsAlthough ultra-Orthodox women have socioeconomic risk factors, breast cancer mortality was lower than non-ultra-Orthodox women. Further research on potential cultural and religious factors influencing mortality is warranted. These findings highlight the importance of evaluating predictors within specific populations.

Abstract B077: Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women

Abstract Background: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who are more likely to die from the disease. To improve our understanding of the relation, we investigated the joint effects of race and neighborhood racial composition, residential mobility, and rurality on the neighborhood deprivation-breast cancer mortality association among White and Black women. Methods: In 2010-2017, 31,358 non-Hispanic White and Black women diagnosed with invasive stage I-IIIA breast cancer were identified by the Georgia Cancer Registry and were followed through 2019 for breast cancer mortality. The neighborhood deprivation index (NDI) was derived through principal component analysis of 2011-2015 block group-level American Community Survey (ACS) data on poverty, income, housing, unemployment, occupation, and education. Neighborhood racial composition and residential mobility were measured using 2011-2015 ACS data. Rurality was measured using Georgia Department of Public Health data. We used Cox proportional hazards regression to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for the association between NDI, in quintiles, and breast cancer mortality, overall and according to joint effects of race and neighborhood characteristics (neighborhood racial composition, residential mobility, and rurality). Results: During follow-up, 2,353 (1,347 non-Hispanic White, 1,006 non-Hispanic Black) women died from breast cancer. Living in the most deprived neighborhoods was associated with a 30% increased risk of breast cancer mortality (quintile 5 vs. 1: HR=1.30, 95% CI 1.13-1.49). The association was present among non-Hispanic White (quintile 5 vs. 1: HR=1.47, 95% CI 1.20-1.79) but not non-Hispanic Black women. We observed similar race-specific patterns when assessing jointly stratified associations. For example, among non-Hispanic White women, neighborhood deprivation was associated with breast cancer mortality irrespective of the additional neighborhood characteristics considered, with the strongest association observed among non-Hispanic White women living in the most deprived rural neighborhoods compared to those living in the least deprived urban neighborhoods (HR=1.70, 95% CI 1.30-2.22). In contrast, no association was found among non-Hispanic Black women in any strata of neighborhood racial composition, residential mobility, or rurality (non-Hispanic Black women living in the most deprived rural neighborhoods vs. those living in the least deprived urban neighborhoods: HR=1.05, 95% CI 0.78-1.41). Conclusions: Consistent with previous studies, our study found that living in a deprived neighborhood may increase breast cancer mortality among non-Hispanic White but not non-Hispanic Black women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women. Other factors beyond neighborhood may contribute to the high breast cancer mortality rate among this racial group. Citation Format: Lauren E. Barber, Leah Moubadder, Maret L. Maliniak, Jasmine M. Miller-Kleinhenz, Jeffrey M. Switchenko, Lauren E. McCullough. Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B077.

Interest in mammography across European countries: a retrospective "Google Trends" comparative study.

Breast cancer is currently the most prevalent and impacting cancer among women and mammography has been recommended for screening by The European Commission Initiative on Breast Cancer since 2003. The objective of this study is to estimate the interest in breast cancer screening breast cancer in European countries by analyzing data from online searches for the term "mammography" obtained via Google Trends. The relative search volumes (RSVs) of the term "mammography" translated into various languages and relating to the January 2010-December 2022 period were downloaded from Google Trends. The between-countries differences growth of interest was estimated by a regression model in which the country-time interaction term was introduced. France [coefficient (coeff): 0.23; 95% confidence interval (CI): 0.18-0.28], United Kingdom (coeff: 0.22; 95% CI: 0.18-0.27) and Germany (coeff: 0.21; 95% CI: 0.16-0.25) showed the higher growth in mammography interest when compared to the average growth. The lowest growths were observed in Eastern European countries: Croatia (coeff: -0.13; 95% CI: -0.18 to -0.09), Serbia (coeff: -0.14; 95% CI: -0.18 to -0.09), Greece (coeff: -0.14; 95% CI: -0.18 to -0.09), Slovenia (coeff: -0.15; 95% CI: -0.2 to -0.11) and Bosnia-Herzegovina (coeff: -0.15; 95% CI: -0.2 to -0.11). These exploratory findings suggest that online interest in mammography is lower in countries with lower screening coverage and higher breast cancer mortality. These countries could adopt strategies to raise awareness of breast cancer prevention.

Apoptosis-inducing, anti-angiogenic and anti-migratory effects of a dinuclear Pd(II) complex on breast cancer: A promising novel compound

Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer.

THU486 Identification Of Metabolic And Molecular Mechanisms Driving Estrogen Receptor Positive Breast Cancer Disparities Using A Machine-Learning Pipeline

Abstract Disclosure: A. Santaliz Casiano: None. D. Mehta: None. H. Patel: None. G. Rauscher: None. J. Kim: None. J.M. Frasor: None. K. Hoskins: None. Background: African American (AA) women in the United States have a 40% higher breast cancer mortality rate compared with Non-Hispanic White (NHW) women. The survival disparity is particularly striking among ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ positive breast cancer. Methods: We collected pretreatment plasma from AA and NHW ER+ breast cancer cases and cancer-free controls to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Statistical methods combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from TCGA. Results: We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed changes in metabolites associated with amino acid metabolism, while fatty acid metabolism was significantly enriched in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant association with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene NELFE with histone methyltransferase activity was associated with poor survival exclusively for AA individuals. Conclusion: We employed a comprehensive and novel approach that integrates multiple machine learning methods and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women, and may ultimately lead to identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer, and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities. Presentation: Thursday, June 15, 2023