Breast Cancer Risk Research Articles

Abstract A036: Hair relaxers use and breast cancer risk by tumor estrogen receptor status: Results from the Ghana Breast Health study

Abstract Background: Hair relaxer use is highly prevalent among women of African descent world-wide and in previous analyses within the Ghana Breast Health Study (GBHS) ever use was associated with a 60% elevated risk of breast cancer. Subsequent studies in the GBHS showed selected alterations in estrogen metabolites with hair relaxer use among controls, suggesting a possible hormonal mechanism may underlie the relation of hair relaxers to breast cancer risk. We investigated if the association between relaxer use and breast cancer risk differed by tumor estrogen-receptor (ER) status and hypothesized ever-users would be at a higher risk of ER+ tumors. Methods: The GBHS is a population-based case-control study conducted between 2013– 2015 in Accra and Kumasi of 1,071 cases with pathologically confirmed invasive breast cancer and 2,106 controls, aged 18-74 years. A standardized interview-based questionnaire collected information on currency and duration of use of hair relaxers and whether products used were lye or non-lye formulations. ER status was available for 915 cases, determined using either mRNA expression data from nCounter® Breast Cancer 360™ Panel (65% of 915 cases) or immunohistochemistry. We used multivariable multinomial logistic regression models to estimate odds ratios (OR) with 95% confidence intervals (CI) for ER+ vs. ER- breast cancers. Models were adjusted for age, hospital site, education, body size, age at menarche, parity, age at first birth, median breastfeeding months/child, menopausal status. To determine if risk related to exposure to relaxers differed by ER status, we used logistic regression analyses with ER+ tumors as the reference and calculated heterogeneity p-values (p-het). Results: The majority of women reported ever use of relaxers (96% of cases and 94% of controls). Of the 1,071 cases included in analyses, 422 (44%) were ER+, 438 (41%) ER-, and 156 (15%) unknown for ER. Elevated risk did not differ by ER status for ever compared to never use (OR ER+ =1.67, 95% CI [0.95–2.93]; OR ER - =1.59, 95% CI [0.92–2.76], p-het=0.90). Risks were highest among former users (OR ER+ =2.19, 95% CI [1.21–3.95]; OR ER- =2.21, 95% CI [1.24–3.93], p-het=0.98. Additional analyses showed elevated risk for those with long durations of use, and those who predominantly used non-lye products, but associations did not differ according to ER tumor status. Conclusion: Our analysis of relaxer use in Ghanaian women showed elevated breast cancer risk, particularly for former, long-term users of non-lye formulations, irrespective of tumor ER status. Additional analyses by tumor and other characteristics related to biologically aggressive tumor types needed to determine if associations differ beyond ER consistent with disparities seen in African ancestry women. Further, future research is warranted regarding specific products used that may provide insights into hormonal and non-hormonal mechanisms underlying observed associations. Citation Format: Kaitlin E. White, Quiera Booker, Nicholas Titiloye, Lawrence Edusei, Louise Brinton, Beatrice Wiafe, Ernest Adjei, Jonine Figueroa, On behalf of the Ghana Breast Health Study Team. Hair relaxers use and breast cancer risk by tumor estrogen receptor status: Results from the Ghana Breast Health 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 A036.

Abstract A103: Feasibility of using data from the All of Us Research Program to better understand Asian American breast cancer risk

Abstract Asian Americans (AAs) are the only racial/ethnic group in the United States for whom cancer is the leading cause of death. In AA women, the rate of breast cancer (BC) has significantly increased in the past two decades. However, the reasons behind the observed increase in risk are not well understood. The All of Us (AoU) Research Program aims to enroll one million participants nationwide, focusing on including individuals from diverse backgrounds, to advance precision health research. The goal of this pilot study was to evaluate the feasibility of using AoU data to analyze factors potentially associated with breast cancer risk in AAs and to develop enhanced breast cancer prediction models. There were 3,433 self-reported AA women with available genomic data. In addition to the genomic data, data was available from surveys, participants’ electronic health records (EHRs), and physical measurements taken at the time of their study visit. BC cases were identified by self-report on surveys (n=38), EHR diagnosis data (n=104), or both survey and EHR (n=59), totaling 201 cases identified. Of these, only 17 were incident cases. Of the 163 cases detected in the EHR, 96.3% were invasive BCs, and the median age at diagnosis was 54.2 (±12.6) years. Among the 38 survey-only-identified cases, age at diagnosis was unclear due to the large age ranges (e.g.18-64 years) in the categories presented in the survey. For purposes of the case-control analysis, five AA women with no BC diagnosis were matched to each BC case by age group and geographic region. Body mass index, annual household income, marital status, history of alcohol consumption, and history of cigarette smoking and vaping were not statistically significantly different between cases and controls (a=0.05). One third (34.3%) of cases were born in the U.S. and 65.2% were born in another country vs. 25.0% and 74.0% of controls, respectively (p= 0.01). Employment status was also different, with 50.8% of cases being unemployed vs. 42.0% of controls (p=0.02). There appeared to be a difference in first-degree family history of BC (reported in 8% of cases vs. 5% of controls) although the results were not statistically significant (p=0.08). However, family history of BC data was not available for 43.3% and 51.0% of the cases and controls, respectively. Gynecologic factors, such as ages at menarche and menopause, and hormone use, were not asked in the surveys and were not widely captured in the EHR data. In our analysis of nine BC- associated genes (BRCA1, BRCA2, ATM, TP53, PTEN, CHEK2, CDH1, PALB2, STK11), pathogenic variants were identified in 1.0% of cases and 0.7% of controls. In summary, the AoU data set enables the study of a diverse national cohort with rich genomic data. However, the low representation of AAs, small numbers of incident cases, limited data on personal gynecologic history, cancer family history and social determinants of health, and broad categorization of age at diagnosis present challenges to using this data to build accurate and effective risk prediction models for BC risk in AAs. Citation Format: Catalina Haas Garcia, Wen-Pin Chen, Danni Liu, Alice W Lee, Min Zhang, Argyrios Ziogas, Sora Tanjasiri, Hannah Lui Park. Feasibility of using data from the All of Us Research Program to better understand Asian American breast cancer risk [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 A103.

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<0.05). In adjusted dosage models, participants showed improved knowledge, attitudes, and EB information sharing (p<0.05). SN members showed improved attitudes and behavior change based on participant EB information sharing on healthy eating (p<0.05). In addition, there was a high concordance between participant EB information sharing and SN EB information learned (>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.

Abstract B070: Addressing health disparities around breastfeeding: Development of a braided curriculum

Abstract Purpose: Breastfeeding initiation and longer duration are known to reduce risk of breast and ovarian cancer. While racial disparities in breast cancer diagnosis and mortality rates exist in the United States, disparate rates of breastfeeding initiation and duration continue to widen. The positive effects of these community lactation support through peer education programs among Black mothers have been demonstrated, but these programs are limited by the lack of reach to vulnerable families. Integration of lactation education and support within parenting programs targeting complementary maternal behaviors, such as psychosocial stress does not exist. This proof-of-concept study uses novel Systematic Braiding methodology to develop an integrated maternal behavior parenting curriculum. Methods: In line with the systematic braiding technique, key stakeholders of two evidence based programs, Intergen (a culturally competent breastfeeding peer-educator program) and SafeCare® (a widely disseminated evidence-based parenting program), were consulted to identify core program components, shared and unique theoretical constructs, and programmatic targets including: population of interest, behaviors, delivery mode, program content, dose and length, assessment, fidelity monitoring. Results: 10 program developers and content experts identified shared and unique theoretical constructs and programmatic targets including: population of interest – at-risk minority parents, behaviors (parenting, breastfeeding, and cancer prevention), delivery mode (in person and self-guided), program content, dose and length, assessment, and fidelity monitoring. Areas of integration were captured to inform the braiding of the new curriculum based in social cognitive theory and the theory of planned behavior including modules on cancer education, prevention through breastfeeding, and screening were captured to inform the braiding of the new curriculum. Future directions will assess the acceptability and feasibility of the braided curriculum via user-centered feedback across informants from each of four key informant groups: 1) target recipients of the curriculum including Black women, <36 weeks gestation; 2) potential program providers; 3) community health care professionals; and 4) state-level legislative representatives. Interim findings will be presented. Discussion: There is limited exploration on using widely disseminated parenting programs to increase breastfeeding uptake among African American mothers. This study takes first steps towards developing a robust intervention to increase the reach of breastfeeding education to expecting African American mothers through a widely disseminated parenting model. Improving knowledge of cancer prevention through breastfeeding along with behavior (initiation and duration) among this at-risk population may positively impact breast and ovarian cancer risk. Citation Format: Marlo Vernon, Ashwini Tiwari, Elinita Pollard, Biplab Datta, Zach Hoffman, Kate Guastaferro, Shannon Self-Brown. Addressing health disparities around breastfeeding: Development of a braided curriculum [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 B070.

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<.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<.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<.01). Community poverty level was indirectly associated with the level of MIP1b through HTN status (p<.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 C003: Multimodal and multiplexed spatial regulation of the breast collagen proteome: Comparative analysis in Black and White women from normal breast tissue and triple-negative breast cancer

Abstract Non-Hispanic Black women (BW) are diagnosed with more aggressive breast cancer subtypes at younger ages and have higher mortality rates compared to non-Hispanic White women (WW). Within the breast microenvironment emergent data shows that stromal collagen plays a significant role in aggressiveness of breast cancer linked to ancestral traits. However, the molecular composition of collagen stroma has yet to be linked to ancestry and aggressiveness of breast cancer. The purpose of this study was to evaluate the microenvironment within ancestry-defined normal breast and triple-negative breast cancer (TNBC) to understand spatial regulation of collagen stroma that may link to ancestral differences in cancer. Multimodal, multiplexed spatial analyses were performed. Techniques included Second Harmonic Generation (SHG) to measure collagen fibers, mass spectrometry imaging to measure the collagen proteome, and mass-tagged antibody panels to investigate immune signatures in TNBC. Normal breast tissues were obtained from the Susan G. Komen Tissue Bank, African American (AA; n=20) and European American (EA; n=20) samples were annotated with risk scores, age, Body Mass Index (BMI), Breast Imaging-Reporting and Data System (BI-RADS), continental ancestry, and family history. Triple-negative breast cancer (TNBC, n=80) tissues from BW with extensive clinical annotations including age, BMI, stage, metastasis, and survival were evaluated in comparison to 20+ TNBC tissues from WW. In the normal breast cohort, evaluation of BMI (overweight and obese) within ancestry groups showed significant but opposing differences in fiber width measurements. As BMI increases, AA showed statistically thicker fibers while EA showed statistically thinner fibers. At the protein level, two types of collagens were significantly higher in EA and one type is higher in AA. Within the TNBC cohort, collagen fiber length and width measurements by SHG were significantly shorter and thinner in stage II compared to stage I but no other stage comparisons were significant. This may indicate that ECM remodeling occurs at earlier stages in TNBC. Initial analyses showed that collagen peptide intensities significantly vary by TNBC stage (75 peptides, ANOVA test FDR p-value < 0.05). In the cohort of women who survived, 90 ECM peptides significantly correlated with collagen fiber widths, indicating a relationship between collagen physical and molecular properties within a defined region. Seven immune markers defined differences in survival when grouped by high vs low expression within tumor regions. These markers include CD20 (Hazard Ratio HR = 7.99, p-value = 0.002) and PD-1 (HR = 3.68, p-value = 0.048), which have both been studied in breast cancer. Current work focuses on collagen peptide post-translational modifications that may differ in TNBC patients by vital status and are detected in normal breast at risk of cancer. These findings support that molecular composition in breast stroma contributes to aggressive ancestral traits of breast cancer risk and triple-negative breast cancer. Citation Format: Jaclyn B. Dunne, Heather Jensen-Smith, Laura Spruill, Taylor S. Hulahan, Jade K. Macdonald, George E. Sandusky, M. A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Jeffrey R. Marks, Harikrishna Nakshatri, Marvella E. Ford, Peggi M. Angel. Multimodal and multiplexed spatial regulation of the breast collagen proteome: Comparative analysis in Black and White women from normal breast tissue and triple-negative breast 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 C003.

Abstract B087: Inflammation and breast cancer: Understanding the interplay and implications for prevention and treatment

Abstract Breast cancer continues to be a major global health issue, affecting millions and posing challenges for researchers and healthcare workers. Recent research has revealed the importance of inflammation in the development and progression of a variety of malignancies, including breast cancer. The aim of this study is to investigate the complex association between inflammation and breast cancer in order to improve treatment and preventative techniques. A mixed-methods approach was used, with both quantitative and qualitative studies. The study included 580 breast cancer patients and 2,573 control participants. Patient records, hospital databases, and publicly available datasets were all used as data sources. Statistical methods, including univariate and multivariate logistic regression models, were employed to discover breast cancer predictors associated with inflammation. Breast cancer growth is strongly linked to chronic inflammation and specific inflammatory markers (CRP, IL-6, and TNF-α). Breast cancer incidence is correlated with geographical, demographic, and lifestyle characteristics such as region, age, gender, race, education level, and overall health condition. Comorbidities like hypertension, diabetes, and arthritis, as well as BMI, smoking, and physical activity levels, all have a role in risk. Anti-inflammatory drugs and lifestyle changes show promise for lowering the risk of breast cancer and improving patient outcomes. The study reveals significant relationships between breast cancer incidence and a variety of demographic, lifestyle, and health-related variables. Chronic inflammation is important in the development of breast cancer; therefore, inflammatory indicators could be used as diagnostic or therapeutic tools. The study suggests that tailored anti-inflammatory medications and lifestyle changes could have a significant impact on breast cancer prevention and therapy. This study emphasizes the necessity of knowing the relationship between inflammation and breast cancer. The insights revealed can lead to novel methods for breast cancer management, stressing the importance of ongoing research to fully understand the connection between inflammation and breast cancer and to implement these discoveries in clinical practice. Citation Format: Opeyemi O. Ogungbola, Samuel O. Ejeh, Jane Odeh, Olajumoke R. Omoniyi, Abayomi A. Akomolafe, Emmanuel K. Abudu. Inflammation and breast cancer: Understanding the interplay and implications for prevention and treatment [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 B087.

Abstract A050: The impact of air pollution on aggressive breast cancer prognoses in women of African descent

Abstract Significance. Breast cancer (BC) is the most diagnosed cancer among women in the US. Though highly heterogeneous, different subtypes can be characterized by the expression of membrane receptors on the cell surface: ER+, HER2+, PR+, or basal-like which does not express any of the three receptors. Basal-like triple-negative breast cancer (TNBC) is a highly aggressive subtype of BC that represents about 15% of overall BC cases. Black women disproportionately experience higher rates of early-onset TNBC phenotypes and worse prognoses when compared to White women. Though genetics is a key factor in oncogenesis and cancer progression, it is now widely recognized that differences in cancer outcomes are influenced, also, by various environmental, social, and lifestyle factors known collectively as the social determinants of health (SDOH). For example, air pollution has consistently been shown to be associated with an increased risk of breast cancer, however, little is known about how air pollution alters biological and molecular mechanisms impacting breast cancer progression. Elucidating these influential factors is critical to understanding and addressing disparate outcomes. We are interested in understanding how air pollution impacts immune-oncology related proteins in breast cancer, specifically for Black and White women living in Baltimore City, Maryland. Methods. In a cohort of 217 women (142 Black, 75 White), we performed statistical analyses to determine the correlation between particulate matter 2.5 (PM2.5) with breast cancer subtype and oncogenic molecular drivers within the tumor and its microenvironment. PM2.5 concentration for Census year 2000 was measured using the EPA Downscale Model. Concentrations at the census-tract level were then linked to each participant's geocoded residential address at study baseline. Results. [BJ1] Our data reveal that a higher exposure to PM2.5 is correlated with breast cancer subtypes incidences[BJ2] (p- value[BJ3] =0.051), specifically for hormone receptor positive (ER+ and/or PR+) and TNBC subtypes (p-value=0.035). Elevated air pollution is also associated with estrogen-receptor status overall (p-value=0.002) and in Black (p-value=0.043) and White (p-value=0.008) women in the stratified analysis. Serum protein measurements in this cohort also revealed significant relationships between elevated air pollution and immune-oncology related proteins, including PD-L1, CAIX, CXCL9, and MCP-2.Discussion. Our preliminary evidence reveals an association between air pollution, breast cancer subtypes, and immune-oncology related proteins, with some of these relationships affecting Black and White populations differently. We will continue to interrogate these differences and begin to reveal the underlying mechanisms exacerbating breast cancer disparities. Citation Format: Kayla S. Ingram, Brittany Jenkins-Lord. The impact of air pollution on aggressive breast cancer prognoses in women of African descent [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 A050.

Abstract A014: Racial and socioeconomic disparities in breast feeding and the impact of pregnancy-related medical conditions among a population-based sample of non-Hispanic Black and White women

Abstract Background: Breastfeeding has been associated with a reduced risk of breast cancer (BC), particularly with Triple Negative BC (TNBC). The risk of TNBC is higher among premenopausal women, Black/African American (AA) women, and poorer women. Notably there are significant disparities in breastfeeding, where non-Hispanic Black (NHB) women and poorer women are less likely to breastfeed in the United States. Studies have identified historical racial trauma, unsupportive work and hospital policies, breast milk formula advertising, and knowledge and beliefs about breast feeding as factors that contribute to breast feeding practices. However, there is a paucity of research on pregnancy related medical conditions (PMCs) that potentially impact initiation and duration of breastfeeding. The purpose of this study is to evaluate racial and socioeconomic differences in breastfeeding, and if PMCs impact breastfeeding practices in a population-based sample of non-Hispanic Black and White women. Method: Data are from the Young Women’s History and Health Study (YWHHS), a population- based case-control study of invasive BC among non-Hispanic Black (NHB) and non-Hispanic White (NHW) women aged 20-49 years residing in Metropolitan Detroit and Los Angeles County, 2010-2015. The analytic sample here includes the first pregnancy of control participants with singleton live births (n=675). Area-based control participants were sampled from the 2010 Census. Interviews assessed complete reproductive histories, including breastfeeding history (never, <6 months, and ≥6 months), PMCs experienced during pregnancy, self-reported race, and household financial struggles before age 13 years (to approximate childhood socioeconomic position (chSEP)). PMCs examined included: 1) premature birth, 2) diabetes or pre-diabetes related PMCs, 3) blood pressure-related PMCs, and 4) BMI ≥ 25 kg/m2 at age 18 years. Weighted percentages were evaluated with a chi-square test and considered significant at p < 0.05. Analyses were further stratified by race/ethnicity and chSEP. Result: NHB women were 2.4 times significantly more likely to never breastfeed than NHW women (W% =52.0 (NHB) and 21.3 (NHW), p=<0.0001). Similarly, women with lower compared to higher chSEP were 1.5 times significantly more likely to never breastfeed (W% = 42.7 (lower chSEP) and 28.5 (higher chSEP), p=0.003). Those with BMI ≥ 25 kg/m2 at age 18 years (p<0.001) alone, and with one or more PMCs (p=0.01) were also less likely to breastfeed. When stratified by race/ethnicity the pattern of breastfeeding did not differ significantly by any PMC within NHB and NHW women. When stratified by chSEP, however, BMI ≥ 25 kg/m2 at age 18 years (p = 0.004) and having one or more PMCs (p=0.03) were significantly associated with never breastfeeding among those with higher chSEP. Conclusion: NHB women and women with lower chSEP were substantially less likely to breastfeed. Additionally, BMI ≥ 25 kg/m2 at age 18 and PMCs were associated with lower frequency of breastfeeding overall and among those with higher chSEP. Citation Format: Meheret B. Gebreegziabher, Lydia R. Post, Chris C. Cho, Zhenzhen Zhang, Kelly A. Hirko, Dorothy R. Pathak, Ann S. Hamilton, Ann G. Schwartz, Ellen M. Velie. Racial and socioeconomic disparities in breast feeding and the impact of pregnancy-related medical conditions among a population-based sample of non-Hispanic Black and White 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 A014.

Abstract A053: Exploring the co-occurrence of historic redlining and present-day breast cancer risk factors

Abstract Background: Historic redlining, a 1930s-era form of residential segregation, has been associated with breast cancer related outcomes, but research is lacking on how known present-day breast cancer risk factors are related to historic redlining. Objective: To describe the co-occurrence of historic redlining with present-day neighborhood-level breast cancer risk factors and evaluate geographic patterning across the US. Methods: All US neighborhoods historically graded (grades A-D) were included. We dichotomized neighborhoods as redlined if they had a historic redlining score ≥2.5 (grades C and D). We used census tract-level prevalence data from 2019 Population Level Analysis and Community EStimates (PLACES) and 2014-2016 air pollution data from Environmental Justice Index (EJI). Neighborhoods were classified as high risk for each factor if they were in the highest two quintiles for adverse risk factors: obesity, binge drinking, smoking, no leisure physical activity (LPA), lacking health insurance, high school education, low median income, concentrated Black population, and air pollution; in the lowest two quintiles of protective factors: mammography and routine checkup; and if the built environment is old (median year houses built <1980). We estimated tetrachoric correlations and conducted a factor analysis to group variables. We created an overall risk score and domain-specific scores for each neighborhood to quantify the number of factors that met the high-risk threshold. Averages of these scores were evaluated according to redlining status. Finally, we used GIS to spatially examine the co-occurrence of high-risk status and redlining. Results: Redlining status was moderately correlated with smoking, no LPA, high school education, low income, and lacking health insurance and was weakly correlated with binge drinking, obesity, concentrated Black population, low mammography, low routine checkup, air pollution, and old built environment. Correlations between social and behavioral factors were strong but weak for healthcare and environmental factors. We identified two domains through factor analysis: (1) behavioral + socioeconomic status (SES) and (2) healthcare. Air pollution and old built environment did not load onto either domain. Across the US, redlined neighborhoods scored significantly higher on all present-day neighborhood risk scales than non-redlined neighborhoods: 30.8% higher on the overall scale, 31.8% higher on the behavior + SES subscale, and 16.4% higher on the healthcare subscale. Maps showed that high-scoring neighborhoods tended to overlap with historically redlined, particularly D-grade, neighborhoods, though there was heterogeneity in patterns depending on scale and US region. Discussion: Redlined neighborhoods have more high-level breast cancer risk factors compared to non-redlined neighborhoods. Our findings suggest that associations between historic redlining and specific factors may be region-dependent, therefore interventions aimed at reducing redlining-based cancer disparities may need to be tailored to the community. Citation Format: Sarah M. Lima, Tia M. Palermo, Helen CS Meier, Jared Aldstadt, Henry L. Taylor Jr, Lili Tian, Heather M. Ochs-Balcom. Exploring the co-occurrence of historic redlining and present-day breast cancer risk factors [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 A053.

Abstract A027: Ethnic variations in breast cancer risk factors distribution in Guam, HIPIMR study

Abstract Background: Guam has significant ethnic disparities in breast cancer incidence, with rates varying from 46.7 per 100,000 among Asian women to 137.5 per 100,000 among Micronesian women. Incidence rates for Filipino, CHamoru (indigenous people), and White women are 59.8, 94.0, and 121.9 per 100,000, respectively (2013-2017). The Hawai‘i and Pacific Island Mammography Registry (HIPIMR), a collaborative effort between the University of Hawai‘i Cancer Center and the University of Guam Cancer Research Center, collects health and breast imaging data to enhance early cancer detection tailored to the unique ethnic profiles of women in Hawai‘i and Guam. This study aims to identify the distribution of breast cancer risk factors among different ethnic groups in women undergoing screening in Guam. Differences in the prevalence of risk factors may explain variations in incidence patterns. Methods: This study included 1,413 women undergoing mammography screening at FHP Health Center in Guam, from November 2023 to May 2024. The risk factors were classified as follows: BMI (≥25), age of menarche (≤13), age of first pregnancy (≥30), number of live births (≤1), age of menopause (≥55), and family history of first-degree relatives. The robust Poisson method was used to estimate prevalence ratios (PR) of risk factors among ethnic groups, adjusted for age and education. Asians were used as the reference group due to their lowest incidence rates. Furthermore, the total risk score was calculated by summing all the risk factors. ANOVA was used to test the differences in average risk scores among different ethnic groups. Results: All ethnic groups had significantly higher prevalence of being overweight or obese compared to Asian women. The prevalence ratios were highest for Micronesians (PR=1.73, 95% CI: 1.40, 2.13) and CHamoru (PR=1.55, 95% CI: 1.27, 1.90). CHamoru women had the highest rates of breast cancer family history (PR=1.74, 95% CI: 1.19, 2.54). However, CHamoru women had a lower prevalence of having a small number of live births (PR=0.39, 95% CI: 0.24, 0.65) and an older age at first birth (PR=0.83, 95% CI: 0.71, 0.96) when compared to Asian women. There was a significant difference in average score among ethnic groups (P<.001). CHamoru women had significantly higher score (2.35) than Filipino (2.08) and Asian (2.00) women. Conclusion: Our study reveals disparities in risk factors across ethnic groups, consistent with the Guam Cancer Registry's reports of high breast cancer rates among Micronesian and CHamoru women. This project is ongoing, with the aim of linking our data with the Guam Cancer Registry. This linkage will enable us to identify breast cancer cases among participants and compare risk factors across different ethnic groups for women with and without breast cancer. Acknowledgement: This research was funded by the National Cancer Institute: The University of Guam/University of Hawaii Cancer Center Partnership to Advance Cancer Health Equity, Grant U54CA143728 (University of Guam, YCP)/Grant U54CA143727 (University of Hawaii Cancer Center). Citation Format: Gian Paras, Su Bin Jin, Rose Grino, Cabrini Aguon, John Shepherd, Grazyna Badowski. Ethnic variations in breast cancer risk factors distribution in Guam, HIPIMR 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 A027.

Abstract C144: Poor survival in non-Hispanic Black HR+/HER2- and HR-/HER2+ breast cancer patients at an NCI-Designated Comprehensive Cancer Center

Abstract Introduction: In the US, 1 in 8 women face a breast cancer diagnosis within their lifetime. While this disease is pervasive, it does not affect all groups of women equally. Non-Hispanic Black (NHB) populations tend to have worse survival outcomes than Non-Hispanic White (NHW) and Hispanic (H) populations. Studying this disparity presents challenges, as it is influenced by many social and biological factors, including quality of cancer care. By comparing NHB, NHW, and H breast cancer patients at Moffitt Cancer Center (MCC), we can describe various factors related to disparate outcomes, while attenuating the effect of varying cancer care settings. Methods: Clinical data (collected from 1986-2018) and patient questionnaire data (collected from 2012-2020) were acquired from MCC databases. Patients were divided into NHW, NHB, and H groups based on their race and ethnicity. Family cancer history, hormonal contraception use, and HR/HER2 subtype were selected for analysis due to their relevance to breast cancer risk or prognosis. Descriptive statistics, chi-square tests, ANOVA, and Tukey tests were performed as appropriate. Results: On preliminary analysis, NHW patients most frequently report a history of cancer diagnosis in one or more first-degree relatives. This is found when considering all cancer types (p<0.001) as well as specifically considering breast, ovarian, and uterine cancer (p=0.029). Patients also disclosed their hormonal contraception use, with 38% of NHW patients reporting an age at which they began using hormonal contraception compared to only 22% of both NHB and H patients (p<0.001). Among those who have used hormonal contraception, there was no significant difference in age of use onset, or total years of use. Significant differences in HR+/HER2-(p<0.001) and HR-/HER2- (p<0.001) frequency were seen between groups. NHB women had the lowest frequency of HR+/HER2- cancers (57%), and the highest frequency of HR-/HER2- cancers (27%). HR-/HER2+ NHB patients displayed significantly worse overall survival relative to NHW (p<0.001) and H (p=0.014) patients of the same subtype. HR+/HER2-NHB patients also have significantly worse overall survival relative to NHW (p=0.010) and H (p=0.010) patients of the same subtype. No significant difference in between-group overall survival is found for the HR-/HER2- and HR+/HER2+ patients. Conclusion: The cohorts in this study provide an opportunity to analyze characteristics and outcomes in breast cancer patients at an NCI-Designated Comprehensive Cancer Center. Higher rates of family cancer history in NHW women and higher rates of HR-/HER2- disease in NHB women align with the literature. NHW patients more frequently reported hormonal contraception use, while showing similarities to NHB and H groups in age and length of use. Despite comparable survival in two HR/HER2 subtypes, HR-/HER2+ and HR+/HER2- NHB women have significantly worse survival than NHW and H women. Further analyses of risk/prognostic factors and treatment regimens are needed to better understand this concerning survival finding. Citation Format: Abigail E. Lantz, Jiannong Li, Ryan F. Gebert, Dung-Tsa Chen, Edna R. Gordián, W. Douglas Cress. Poor survival in non-Hispanic Black HR+/HER2- and HR-/HER2+ breast cancer patients at an NCI-Designated Comprehensive Cancer Center [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 C144.

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 & Sift, Think & 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.

Enhancing Breast Cancer Risk Prediction with Machine Learning: Integrating BMI, Smoking Habits, Hormonal Dynamics, and BRCA Gene Mutations—A Game-Changer Compared to Traditional Statistical Models?

Enhancing Breast Cancer Risk Prediction with Machine Learning: Integrating BMI, Smoking Habits, Hormonal Dynamics, and BRCA Gene Mutations—A Game-Changer Compared to Traditional Statistical Models?

WHO-recommended levels of physical activity in relation to mammographic breast density, mammographic tumor appearance, and mode of detection of breast cancer

BackgroundDespite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD).MethodsPhysical activity levels from study baseline (1991–1996) and mammographic information from the time of invasive breast cancer diagnosis (1991–2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used. Duration and intensity of physical activity were assessed according to metabolic equivalent of task hours (MET-h) per week, or World Health Organization (WHO) guideline recommendations. MBD was dichotomized into low-moderate or high, MA into spiculated or non-spiculated tumors, and MoD into clinical or screening detection. Associations were investigated through logistic regression analyses providing odds ratios (OR) with 95% confidence intervals (CI) in crude and multivariable-adjusted models.ResultsIn total, 32% of participants had high MBD at diagnosis, 37% had non-spiculated MA and 50% had clinical MoD. Overall, no association between physical activity and MBD was found with increasing MET-h/week or when comparing women who exceeded WHO guidelines to those subceeding recommendations (ORadj 1.24, 95% CI 0.78–1.98). Likewise, no differences in MA or MoD were observed across categories of physical activity.ConclusionsNo associations were observed between pre-diagnostic physical activity and MBD, MA, or MoD at breast cancer diagnosis. While physical activity is an established breast cancer prevention strategy, it does not appear to modify mammographic characteristics or screening detection.

Dietary soluble, insoluble, and total fiber intake and their dietary sources in association with breast cancer

BackgroundA few studies have examined the association between different types of dietary fiber as well as their sources and the risk of breast cancer (BC) and the present study aimed to investigate these associations in a case-control study among Iranian women.MethodsA total of 464 women with pathologically confirmed breast cancer within the past year and 498 age-matched healthy controls were included. Dietary intakes were assessed using a 168-item food frequency questionnaire. The association between dietary soluble, insoluble, total dietary fiber, as well as, fiber from fruits, vegetables, legumes, cereals, and nuts intake with odds of breast cancer was assessed using multivariate logistic regression analysis.ResultsMean total dietary fiber intake of patients with and without cancer were 33.1 ± 15.3 g per day (g/d) and 34.2 ± 16.5 (g/d), respectively. Dietary total fiber (OR = 0.65; 95%CI: 0.47–0.90, Ptrend = 0.01), insoluble fiber (OR = 0.68; 95%CI: 0.49–0.93, Ptrend = 0.01), fruits’ fiber (OR = 0.68; 95%CI: 0.49–0.94, Ptrend = 0.02), and vegetables’ fiber (OR = 0.66; 95%CI: 0.48–0.91, Ptrend = 0.01) were significantly associated with reduced likelihood of developing breast cancer in all participants. Furthermore, dietary total and insoluble fiber, as well as, fiber from fruits were significantly associated with lower odds of breast cancer in premenopausal women (P < 0.05). In contrast, cereals’ fiber significantly increased the risk of breast cancer by 84% in premenopausal women (OR = 1.84; 95%CI: 1.18–2.86, Ptrend = 0.009). In postmenopausal women, cereals’ fiber had a significant inverse association with odds of breast cancer (OR = 0.56; 95%CI: 0.31–1.03, Ptrend = 0.04). Also, fiber from vegetables was significantly associated with a lower risk of breast cancer in postmenopausal women (OR = 0.53; 95%CI: 0.30–0.94, Ptrend = 0.03).ConclusionDietary fiber intake and more specifically insoluble, fruits’, and vegetables’ fiber intake might be associated with a reduced breast cancer risk, particularly in premenopausal women. Future prospective investigations are needed to confirm these findings.

Regular whole blood donation and gastrointestinal, breast, colorectal and haematological cancer risk among blood donors in Australia

AbstractBackground and ObjectivesSeveral studies have suggested that blood donors have lower risk of gastrointestinal and breast cancers, whereas some have indicated an increased risk of haematological cancers. We examined these associations by appropriately adjusting the ‘healthy donor effect’ (HDE).Materials and MethodsWe examined the risk of gastrointestinal/colorectal, breast and haematological cancers in regular high‐frequency whole blood (WB) donors using the Sax Institute's 45 and Up Study data linked with blood donation and other health‐related data. We calculated 5‐year cancer risks, risk differences and risk ratios. To mitigate HDE, we used 5‐year qualification period to select the exposure groups, and applied statistical adjustments using inverse probability weighting, along with other advanced doubly robust g‐methods.ResultsWe identified 2867 (42.4%) as regular high‐frequency and 3888 (57.6%) as low‐frequency donors. The inverse probability weighted 5‐year risk difference between high and low‐frequency donors for gastrointestinal/colorectal cancer was 0.2% (95% CI, −0.1% to 0.5%) with a risk ratio of 1.25 (0.83–1.68). For breast cancer, the risk difference was −0.2% (−0.9% to 0.4%), with a risk ratio of 0.87 (0.48–1.26). Regarding haematological cancers, the risk difference was 0.0% (−0.3% to 0.5%) with a risk ratio of 0.97 (0.55–1.40). Our doubly robust estimators targeted minimum loss‐based estimator (TMLE) and sequentially doubly robust (SDR) estimator, yielded similar results, but none of the findings were statistically significant.ConclusionAfter applying methods to mitigate the HDE, we did not find any statistically significant differences in the risk of gastrointestinal/colorectal, breast and haematological cancers between regular high‐frequency and low‐frequency WB donors.

Evidence-based neuroprotective potential of nonfeminizing estrogens: In vitro and in vivo studies.

Menopause weakens the brain's structural integrity and increases its susceptibility to a range of degenerative and mental illnesses. 17β estradiol (17βE2) exhibits potent neuroprotective properties. Exogenous estrogen supplementation provides neuroprotection, but the findings presented by the Million Women Study (MWS) and the Women's Health Initiative (WHI), as well as the increased risk of endometrial cancer, breast cancer and venous thromboembolism associated with estrogen use, have cast doubt on its clinical use for neurological disorders. Thus, the objective of our review article is to compile all in vitro and in vivo studies conducted till date demonstrating the neuroprotective potential of nonfeminizing estrogens. This objective has been achieved by gathering various research and review manuscripts from different records such as PubMed, Embase, Scopus, Google Scholar, Web of Science and OVID, using different terms like 'estrogen deficiency, 17β estradiol, non-feminising estrogens, and brain disorder'. However, recent evidence has revealed the contribution of numerous non-estrogen receptor-dependent pathways in neuroprotective effects of estrogen. In conclusion, synthetic nonfeminizing estrogens that have little or no ER binding but are equally powerful (and in some cases more potent) in delivering neuroprotection are emerging as viable and potential alternatives.

Circulating Estrogen Metabolites and Risk of Breast Cancer among Postmenopausal Women in the Nurses' Health Study.

Estradiol and estrone are well-established risk factors for postmenopausal breast cancer (BC). Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at the 2- or 16-position may independently influence carcinogenesis. We performed a nested case-control study of BC (328 BC cases; 639 controls) among postmenopausal women within the Nurses' Health Study (NHS)to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated+conjugated forms) were measured by liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression, adjusting for BC risk factors, estimated relative risks (RR) and 95% confidence intervals (CI) of BC across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen/progesterone receptor (ER/PR) status were analyzed by unconditional logistic regression. Estradiol and estrone were strongly associated with increased BC risk [estradiol: RRQ5v.Q1 (95% CI)=2.64 (1.64-4.26), estrone: 2.78 (1.74-4.45); both p-trends<0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5v.Q1=3.09 (1.81-5.27), p-trend<0.001], and remained so after adjusting for unconjugated estradiol [RRQ5v.Q1=2.23 (1.25-3.96), p-trend=0.01]. While the 16-hydroxylation pathway was modestly associated with risk [RRQ5v.Q1=1.62 (1.03-2.54), p-trend=0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5v.Q1=1.24 (0.77-1.99), p-trend=0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors. In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased BC risk, independent of unconjugated estradiol. These results highlight the need to revisit the role of estrogen metabolism in BC etiology and prevention.

Evaluating Real World Health System Resource Utilization and Costs for a Risk-Based Breast Cancer Screening Approach in the Canadian PERSPECTIVE Integration and Implementation Project.

A prospective cohort study was undertaken within the PERSPECTIVE I&I project to evaluate healthcare resource utilization and costs associated with breast cancer risk assessment and screening and overall costs stratified by risk level, in Ontario, Canada. From July 2019 to December 2022, 1997 females aged 50 to 70 years consented to risk assessment and received their breast cancer risk level and personalized screening action plan in Ontario. The mean costs for risk-stratified screening-related activities included risk assessment, screening and diagnostic costs. The GETCOST macro from the Institute of Clinical Evaluative Sciences (ICES) assessed the mean overall healthcare system costs. For the 1997 participants, 83.3%, 14.4% and 2.3% were estimated to be average, higher than average, and high risk, respectively (median age (IQR): 60 [56-64] years). Stratification into the three risk levels was determined using the validated multifactorial CanRisk prediction tool that includes family history information, a polygenic risk score (PRS), breast density and established lifestyle/hormonal risk factors. The mean number of genetic counseling visits, mammograms and MRIs per individual increased with risk level. High-risk participants incurred the highest overall mean risk-stratified screening-related costs in 2022 CAD (±SD) at CAD 905 (±269) followed by CAD 580 (±192) and CAD 521 (±163) for higher-than-average and average-risk participants, respectively. Among the breast screening-related costs, the greatest cost burden across all risk groups was the risk assessment cost, followed by total diagnostic and screening costs. The mean overall healthcare cost per participant (±SD) was the highest for the average risk participants with CAD 6311 (±19,641), followed by higher than average risk with CAD 5391 (±8325) and high risk with CAD 5169 (±7676). Although high-risk participants incurred the highest risk-stratified screening-related costs, their costs for overall healthcare utilization costs were similar to other risk levels. Our study underscored the importance of integrating risk stratification as part of the screening pathway to support breast cancer detection at an earlier and more treatable stage, thereby reducing costs and the overall burden on the healthcare system.