Living in a disadvantaged neighborhood is linked to higher mortality rates and poorer quality of life (QoL) among patients with breast cancer (BC). Subjective socioeconomic status (SSS), reflecting one’s perceived socioeconomic “rank” or social standing relative to others, may be associated with differences in the relationship between objective neighborhood disadvantage and QoL. Therefore, we sought to evaluate whether SSS moderated the association between objective neighborhood disadvantage and QoL in middle- and older-aged women undergoing BC treatment. Women (≥ 50yrs) diagnosed with non-metastatic BC participating in a stress management trial completed a baseline assessment of SSS (MacArthur Network Sociodemographic Questionnaire) and QoL (Functional Assessment of Cancer Therapy-Breast) in the weeks after surgery. The Area Deprivation Index (ADI), which ranks the degree of neighborhood disadvantage via participants’ addresses, measured objective neighborhood disadvantage. Multivariate linear regressions related ADI, SSS, and QoL, adjusting for age, cancer stage, and race/ethnicity. Greater SSS relative to the community (B = 3.60, SE = 1.12, p=.002) and the USA (B = 3.01, SE = 1.09, p=.006) related to better QoL. Also, SSS USA interacted with ADI in predicting QoL (B = 0.95, SE = 0.45, p=.038), such that greater ADI related to poorer QoL in women with lower but not higher SSS. Greater SSS relative to one’s community and the USA population related to better QoL in women treated for BC. Conversely, greater objective neighborhood disadvantage related to poorer QoL but not among those with greater SSS. Future work could examine whether SSS is a modifiable intervention target through coping effectiveness training, or by enhancing community and social engagement.

Breast cancer is the second leading cause of cancer-related death among American women. Although mammography improves early detection and survival, numerous barriers limit routine screening. These arise at multiple levels—from distal factors such as limited infrastructure and access to imaging centers, to intermediate factors including neighborhood disadvantage and cultural or social beliefs, to proximal factors such as socioeconomic status, and low health literacy stigma. Vulnerable groups, including women with disabilities, LGBTQ+ individuals, and older adults, often face layered challenges. This review examines distal, intermediate, and proximal factors contributing to breast cancer screening barriers. Recent studies highlight persistent inequities in breast cancer screening access and utilization, particularly among marginalized populations. Evidence shows that these barriers operate at multiple levels—distal, intermediate, and proximal—compounding disparities in screening. Reducing breast cancer screening disparities requires multilevel, context-specific interventions that expand access, strengthen education, and promote culturally competent care to improve early detection and outcomes across diverse populations.

BACKGROUND:Triple-negative breast cancer (TNBC) is associated with disadvantaged neighborhoods and at-risk groups. Less is known about how environmental exposures drive TNBC. This study assesses associations of Superfund (SF) site and poor air quality exposure with TNBC. METHODS:A retrospective review was performed for patients with stage I to IV breast cancer treated between 2005 and 2018. SF locations were geocoded and compared with patient addresses to determine proximity. Proximity was defined as <4 miles to the nearest site. Daily maximum particulate matter (PM2.5) measurements were sourced and merged with addresses; high exposure was defined as >35 μg/m3. Multilevel regression analyses controlling for demographic and clinical factors were performed to assess associations among SF proximity, PM2.5 exposure, and likelihood of TNBC compared with other breast cancer subtypes. RESULTS:A total of 3,181 patients with a mean age 56 ± 12 years were included. Eighty percent (n = 2,551) were White, and 20% (n = 630) were Black. Nineteen percent (n = 618) had TNBC. Forty-four percent (n = 1,410) lived close (<4 miles) to SF sites. Two percent (n = 56) had "high" PM2.5 exposure. On multilevel analysis, patients living "close" to SF (OR = 1.33; 95% confidence interval, 1.05-1.67; P = 0.015) and with "high" PM2.5 exposure (OR = 2.09; 95% confidence interval, 1.04-4.02; P = 0.039) had higher TNBC likelihood. CONCLUSIONS:Living near SF sites and having "high" PM2.5 exposure were associated with higher TNBC likelihood. These findings merit further inquiry on the role of environmental contaminants on breast cancer subtype development. IMPACT:Residential exposure to SF sites and high PM2.5 levels may drive aggressive breast cancer biology, including TNBC. See related In the Spotlight, p. 7.

577 Background: African compared to European genetic ancestry is associated with lower prevalence of clinically actionable alterations despite comparable overall prevalence of driver alterations by ancestry group. This likely contributes to breast cancer (BC) disparity. A limitation of prior ancestry studies is lack of neighborhood-level disadvantage (ND) data, a contributor to BC disparity. The objective of this study was to investigate associations between ND and somatic mutations in a real-world BC cohort. Methods: Somatic mutations from primary and metastatic BC samples and genetic ancestry data were identified from MSK IMPACT (FDA-authorized sequencing panel). Samples sequenced between 2015-2025 were annotated and linked with census-tract level socioeconomic status (Yost Index 1-100; higher reflects increasing ND). Multivariate logistic regression analyzed associations between ND and somatic mutations, adjusting for covariates (FDR p<0.05). Results: 6703 samples (62% primary, 38% metastatic) were analyzed. Mean age was 60 (SD 13). Mean Yost was 26 (SD 24). 67% had ER+/HER2- disease, 9.7% had ER+/HER2+, 5.1% had ER-/HER2+, and 19% had ER-/HER2-. Adjusting for age, BMI, ancestry, and subtype, patients from ND had lower odds of CDH1 (OR 0.99, 95% CI 0.98- 0.99, p<0.001), BRCA1 (OR 0.96, 95% CI 0.94-0.99, p=0.021), and AKT1 (OR 0.98, 95% CI 0.97- 0.99, p=0.006) somatic mutations in metastatic samples. Conclusions: We identify novel associations between ND and somatic mutations. Notably, patients with ND had lower odds of actionable BRCA1 and AKT1 mutations. This highlights the importance of ensuring patients of diverse ancestry and ND have equitable inclusion in clinical sequencing workflows to improve identification of actionable mutations in all populations. Genetic ancestry (GA) and somatic mutational frequency by Yost. TotalN=6703 1 Yost 1-20(Most Advantaged)N=3601 1 Yost 21-40N=1539 1 Yost 41-60N=826 1 Yost 61-80N=477 1 Yost 81-100(Most Disadvantaged) N=260 1 p-value 2 European GA* 0.75(0.36) 0.83(0.30) 0.72(0.38) 0.64(0.39) 0.58(0.39) 0.42(0.35) <0.001 African GA* 0.12(0.27) 0.04(0.16) 0.15(0.30) 0.21(0.34) 0.25(0.36) 0.44(0.38) <0.001 East Asian GA* 0.05(0.21) 0.05(0.21) 0.06(0.22) 0.06(0.21) 0.07(0.23) 0.04(0.17) <0.001 South Asian GA* 0.06(0.16) 0.06(0.17) 0.05(0.15) 0.06(0.17) 0.04(0.12) 0.03(0.08) <0.001 Native American GA* 0.03(0.10) 0.01(0.07) 0.03(0.10) 0.04(0.12) 0.06(0.16) 0.08(0.17) <0.001 Mutational Frequency, metastases N=2536 1 N=1403 1 N=584 1 N=311 1 N=165 1 N=73 1 p-value 2 ^ CDH1 341(13%) 220(16%) 66(11%) 26(8.4%) 18(11%) 11(15%) <0.001 AKT1 127(5.0%) 74(5.3%) 34(5.8%) 12(3.9%) 4(2.4%) 3(4.1%) 0.006 BRCA1 21(0.8%) 13(0.9%) 7(1.2%) 1(0.3%) 0(0%) 0(0%) 0.021 *Calculated using >3,000 common SNP markers. ^MVA, control for age, BMI, ancestry, subtype. 1 Mean (SD), n (%). 2 Pearson’s Chi 2 test; Kruskal-Wallis rank sum test; Fisher’s exact test.

OBJECTIVE:To evaluate the association between living in disadvantaged neighborhoods in New York City (NYC) with tumor grade, a clinical proxy for proliferation and tumor aggressiveness, and breast cancer-specific survival (BCSS). BACKGROUND:Neighborhood disadvantage (ND) is associated with shorter BCSS, independent of individual-level, tumor, and treatment characteristics, highlighting unmeasured factors associated with this survival disparity. METHODS:Women with stage I to III breast cancer (BCa) living in NYC treated at Memorial Sloan Kettering Cancer Center from 2013 to 2024 were included. ND was stratified using the Area Deprivation Index (ADI). The median ADI for the cohort was 3 and was used as the cutoff between neighborhood advantage (NA, ADI 1-3) and ND (ADI 4-10). Multivariable logistic regression and Cox proportional hazards modeling, controlling for individual, tumor, and treatment factors, were used to determine the association between ND and tumor grade and BCSS, respectively. RESULTS:Five thousand four hundred fifty-two women with BCa were included. Three thousand four hundred seventy-nine (64%) lived in NA and 1973 (36%) in ND. On multivariable analysis, ND had higher odds of poorly versus well/moderately differentiated tumors (adjusted odds ratio: 1.23, CI: 1.03-1.48), independent of age, race/ethnicity, insurance, body mass index, smoking/alcohol, stage, and subtype. ND was also associated with shorter BCSS (adjusted hazard ratio: 1.56, CI: 1.05-2.38). CONCLUSIONS:Women living in ND in NYC were more likely to present with poorly differentiated tumors and have shorter BCSS. These findings merit further inquiry and lay the foundation for future translational studies to externally validate the mechanisms by which ND "gets under the skin" to impact aggressive BCa tumor biology, and ultimately survival.

Background: To evaluate the impact of Hispanic ethnic enclaves (EE) on the relationship between neighborhood disadvantage and overall survival (OS) in breast cancer (BCa) patients. Methods: Data from BCa patients with stage I-IV disease diagnosed between 2005-2017 was used to analyze the effects of Area Deprivation Index (ADI) scores, a measure of neighborhood disadvantage, and census-tract level Hispanic density, a measure of EE, on OS using mixed-effects Cox regression models. The final model included the following individual-level factors (age, income, race, Hispanic/Latino origin, nativity, insurance status, and comorbidities (hypertension, diabetes, and body mass index) and clinical factors (National Comprehensive Cancer Network guideline-concordant treatment, stage, and receptor subtype). Results: 5,387 patients were analyzed. 52% resided in Hispanic EE. Enclave residents were predominantly White (93%), with Cubans the predominant subgroup (37%). Overall, there were 1,040 deaths within the cohort. Patients residing in highly disadvantaged neighborhoods (ADI Tertile 3 [ADIT3]) within Hispanic EE experienced reduced HR compared to those outside of EE, evidenced by the interaction effect [EE x ADIT3 - HR (95% CI): 0.66 (0.44, 0.98)]. Conclusions: Hispanic EE may protect against mortality in BCa patients, suggesting positive social factors help combat negative effects of neighborhood disadvantage for patients. Understanding protective attributes of EE can help create effective cancer interventions and promote more equitable outcomes in minority populations. Impact: This study found that EE may protect against mortality in BCa patients, suggesting positive social factors may help mitigate the negative effects caused by the neighborhood.

BACKGROUND:Social needs are direct mediators of poor health outcomes. They are actionable targets for physicians and healthcare systems to address. The goal of this study was to evaluate the presence of unmet social needs in breast cancer patients at an NCI-designated academic cancer center (ACC) and its sister safety-net hospital (SNH). METHODS:Prospective cohort study of 336 patients with diagnosed breast cancer administered the Health Leads Social Needs Screening Toolkit. Patient demographics, risk factors, tumor characteristics, and stage-appropriate treatment were analyzed by using chi-square tests and analysis of variance (ANOVA). RESULTS:42% of patients presented to either hospital with one or more unmet social needs. The SNH patients were more likely to present with two or more unmet social needs compared to ACC patients (32% vs. 17%, p = .023), while ACC patients were more likely to present with zero or one unmet social needs compared to SNH patients (61% vs. 47.8% and 22% vs. 20%, respectively, p = .023). The most reported unmet social needs was a Lack of Companionship (17%). Patients who presented to SNH compared with ACC were more likely to report unmet social needs in the domains of Food Insecurity (20% vs. 8%, p = .003), Housing (25% vs. 14%, p = .024), Healthcare Costs (16% vs. 6%, p = .007), and Transportation (17% vs. 5%, p < .001). DISCUSSION:There are significant differences in the presence of unmet social needs in patients who present to different hospital systems. Support systems which address these unmet social needs are important to improve breast cancer health outcomes.

Supplementary Table S3: Differentially expressed small non-coding RNAs.

BACKGROUND:Social adversity from neighborhood disadvantage (ND) is associated with shorter breast cancer survival. Although studies have identified associations between ND and DNA methylation (DNAme) or gene expression (mRNA), a study integrating DNAme and mRNA to understand how the epigenome regulates key biological pathways in ND merits further inquiry. METHODS:DNAme-, mRNA-, miRNA-, and tRNA-derived fragment data were analyzed from 80 estrogen receptor+/HER2- breast cancer samples. We analyzed the association among ND, DNAme, coding, and noncoding data to understand how the epigenome regulates biological pathways. RESULTS:Twenty-five patients lived in ND and 55 in neighborhood advantage. In patients from ND, calcium signaling and cell adhesion pathways were hypermethylated, immune-related pathways hypomethylated, immune response genes upregulated, and estrogen response genes downregulated. Small RNA analysis showed differential expression of miRNA isoforms and tRNA-derived fragments related to ND. Subjective ND further correlated with epigenetic changes in calcium signaling, cell adhesion, and metabolic pathways, along with upregulation of proliferative and stemness pathways. CONCLUSIONS:We discovered novel associations between ND and epigenomic regulation of clinically relevant oncogenesis pathways associated with aggressive biology, such as estrogen response pathways. These findings lay the foundation for multi-institutional studies to validate our findings. IMPACT:This study demonstrates that ND, which is associated with shorter breast cancer survival, is also associated with epigenetic reprogramming of key oncogenesis pathways. These findings highlight pathways through which ND may affect tumor biology and lay the foundation for cancer control policy and behavioral interventions that may reverse the negative effects of ND on cancer biology.

Body image has predominantly been examined among young White women. As a result, the guiding theories in this area of study are based on implicit assumptions that this population’s experience is normative. These assumptions include thinness as the ideal body type and the lack of consideration of body shape, skin tone, and hair texture in body image. As a result, research examining body image among Black women has been limited by using theoretical constructs that do not fully capture the lived experiences of this population. The purpose of the study was to investigate the role of the racialized beauty aesthetic in Black women’s body image. Eight focus groups were conducted with 30 Black women aged 18–29 with a Body Mass Index (BMI) ≥ 25-kg/m2. Focus groups used a semi-structured interview guide to assess race, beauty ideals, pressures to meet the beauty ideals, and the social costs and benefits of obtaining the ideals. We used a constructivist grounded theory approach to develop a conceptual model. This method's steps include initial, focused, and theoretical coding. Results indicated that the standardization of Eurocentric beauty standards resulted in the stigmatization and devaluation of Black women based on appearance. Participants described being stigmatized on the basis of their appearance and feeling devalued due to the prevalence of negative stereotypes about Black women’s appearance and behavior. Experiences of gendered racism resulted in racialized body dissatisfaction. Participants coped with these experiences by engaging in shifting behaviors to reduce the appearance of stigmatizing marks or by rejecting normative Whiteness. Both coping methods came with costs and benefits; participants expressed that they felt they were in a no-win situation, which had adverse health consequences. These findings resulted in the development of the Black Feminist Model of Body Image. Consideration of Black women’s body image in the context of their intersectional marginalized identities highlights how Eurocentric beauty standards are used to perpetuate the stigmatization of Black women. This work implies that efforts to improve the health of Black women must seriously consider the role of body image and racialized body dissatisfaction on their mental and physical health. Body image has mainly been studied in young White women, and body dissatisfaction has been understood as the lack of meeting the beauty ideal of being thin. However, this definition of body dissatisfaction did not capture Black women’s experiences. In this study, we conducted 8 focus groups with thirty Black women to explore how their racial identity influenced their body image. We found that Black women were often criticized and mistreated due to physical appearance attributes such as hair texture, skin tone, and body shape. As a result, some took actions to modify their appearance to blend in better with White women, which helped them in work and school environments but led to them feeling like they were not being authentic. Others chose to embrace their appearance differences but were at a disadvantage in predominantly White environments. All the participants reported that having to navigate these issues on a daily basis had a negative influence on their mental and physical health.

BACKGROUND:Social adversity from neighborhood disadvantage (ND), objectively measured using the area deprivation index, is a known factor contributing to breast cancer disparities and has been associated with heightened psychophysiologic stress response processes, more aggressive tumor biology, and worse disease outcomes. Although many aspects of ND may be less accessible for modification, some subjective experiences of ND may be modifiable through psychosocial intervention. This study investigates a critical gap in the literature with regard to the link between objective ND and potentially modifiable subjective perceptions of ND. METHODS:From 2020 to 2024, 610 adult patients (English-, Spanish-, and Creole-speaking) receiving care for breast cancer at a South Florida NCI-Designated Cancer Center and sister safety-net hospital enrolled in a cohort study and completed measures for neighborhood-level adversity (Neighborhood Social Environment Adversity Survey) and individual-level (Perceived Stress Scale and Impact of Event Scale-Intrusions) perceived stress as well as coping mechanisms (John Henryism Active Coping Scale, Social Provisions Scale, and Management of Current Stress). The area deprivation index was derived from residential addresses. RESULTS:Multiple regression analyses found that: (i) women living in areas of higher objective ND reported greater levels of perceived ND (Neighborhood Social Environment Adversity Survey), (ii) greater subjective ND related to greater general (Perceived Stress Scale) but not cancer-specific stress (Impact of Event Scale-Intrusions), and (iii) women with greater coping mechanisms (John Henryism Active Coping Scale, Social Provisions Scale, and Management of Current Stress) reported lower levels of subjective ND (all P < 0.05). CONCLUSIONS:This study clarified relationships among sources of social adversity, stress, and coping mechanisms. IMPACT:These findings may help inform intervention design for patients with breast cancer living in social adversity.

Background: Florid lobular carcinoma in situ is an uncommon lobular neoplasia variant that is frequently associated with invasive carcinoma. However, there remains a paucity of information to guide management. The authors aimed to study imaging features associated with pathologic upgrade rates for patients with florid lobular carcinoma in situ identified on core biopsy undergoing surgical excision. Methods: Patients with florid lobular carcinoma in situ on core biopsy were selected from an institutional pathology database. Patients were excluded if pleomorphic lobular carcinoma in situ was also present on core biopsy. Clinical, radiologic, and pathologic features for each case were reviewed focusing on imaging features which led to core biopsy and those associated with pathologic upgrade on surgical excision. Results: Eighteen cases of florid lobular carcinoma in situ underwent surgical excision. Upgrade rates on surgical excision were higher in cases with suspicious calcifications (8/11, 73%, p=0.049) compared to those without (1/7, 14.3%) and in cases with larger breast lesions (p=0.011). The overall upgrade rate was 50% (9/18), 89% (8/9) with invasive lobular carcinoma and 11% (1/9) with ductal carcinoma in situ. Of the 8 cases with upgrade to invasive lobular carcinoma, 7/8 (87.5%) were Stage I cancers and only 1/8 (12.5%) had macroscopic lymph node involvement and was upgraded to Stage II. Conclusion: Florid lobular carcinoma in situ on core biopsy had an upgrade rate on surgical excision of 50% overall, with 89% of these cases upgraded to invasive lobular carcinoma. Pathologic upgrade was seen more frequently with suspicious calcifications and larger breast lesions. These findings can help guide surgical management of this uncommon lobular neoplasia variant including planning extent of excision and consideration for lymph node evaluation.

Objective: To determine the association between objective (geospatial) and subjective (perceived) measures of structural racism and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity. Background: Structural racism is associated with shorter breast cancer recurrence-free survival, independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which structural racism influences tumor biology. The field of social genomics offers a mechanistic approach to study the influence of social adversity on tumor biology through validated TFs of social adversity. Methods: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on protocol. Covariate-adjusted multivariable regression analyzed objective measures of structural racism using the validated Index of Concentration at the Extremes and subjective measures of perceived discrimination using the Expanded Everyday Discrimination Survey with validated TFs of social adversity and aggressive biology—pro-inflammatory activity [nuclear factor-κB (NF-kB) and sympathetic nervous system (SNS) activity [cyclic 3′-5′ adenosine monophosphate response element-binding protein (CREB)], controlling for age, race/ethnicity, BMI, stage, grade, tumor type (TNBC, etc), and neoadjuvant therapy. Results: Increasing objective structural racism and perceived discrimination were associated with SNS activation (up-regulated CREB) and aggressive tumor biology (up-regulated NF-kB). Conclusions: To our knowledge, in the largest human social genomics structural racism study, objective measures of structural racism and subjective measures of perceived discrimination were significantly associated with TFs of aggressive biology and SNS activation, implicating SNS activation as one potential mechanism behind structural racism-associated survival disparities. We have previously shown that these TFs correlate with worse clinical outcomes such as shorter survival and higher Oncotype DX scores further reflective of aggressive tumor biology. These findings remain to be validated in a national cohort. Citation Format: Neha Goel, Alexandra Hernandez, Susan Kesmodel, Michael Antoni, Steve Cole. Structural Racism and Aggressive Breast Cancer Biology [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-03-11.