Disparities In Breast Cancer Incidence Research Articles

Abstract PO3-09-11: Age Group Analysis of Breast Cancer Patterns in Brazil: Findings from Population-Based Registries

Abstract Background: The rising breast cancer (BC) incidence among young women is potentially influenced by modifiable genetic and reproductive risk factors, as well as the increased incidence among older women may be associated with lifestyle-related factors and screening programs. This study examines BC incidence and mortality rates across different age groups in Brazil, focusing on clinicopathological and sociodemographic variations. Patients and methods: By using data from 13 Brazilian Population-Based Cancer Registries spanning the period 2010-2015, this study analyzed incidence trends among women with BC. Crude incidence ratios (CIRs) and the annual average percent change (AAPC) were computed. Additionally, clinical and sociodemographic information from 348 Hospital-Based Cancer Registries covering 2000-2019 was incorporated. Mortality data for the years 2000-2020 were obtained from the National Mortality Information System. Comparative analyses were conducted across three predefined age groups: < 40, 40-69, and ≥ 70 years. Statistical significance was defined as a p-value < 0.05, while a threshold of more than 5% difference in proportional values was used as a criterion to identify clinically relevant differentials. Results: Between 2010 and 2015, a total of 205,966 newly diagnosed cases of BC were documented. The CIRs were 7.1/100,000 for the age group < 40, 156.5/100,000 for the age group 40-69, and 247.5/100,000 for the age group ≥ 70 years. Within the scope of the analyzed age groups, it was observed that solely the age group < 40 years exhibited a noteworthy and persistent increase in the rate of occurrence (AAPC +1.6; 95% CI: 1.0 to 2.2; p < 0.001). This age group also displayed a significantly higher proportion of black women (53%, p < 0.001), a higher prevalence of alcohol consumption (20.5%, p < 0.001), and a greater likelihood of receiving multiple treatment modalities (60.7%, p < 0.001). In contrast, the age group ≥ 70 years experienced a more extended time delay of > 60 days from diagnosis to treatment onset (54%, p < 0.001), while exhibiting a higher utilization rate of hormone therapy (45.3%, p < 0.01). The mortality rates witnessed a significant increase across all age categories, with the age group < 40 years manifesting the most substantial escalation (AAPC +1.8%; 95% CI: 1.6 to 2.1; p < 0.001). This rise was comparatively more than double the rate observed in the 40-69 age group (AAPC +0.7%; 95% CI: 0.5 to 0.8; p < 0.001) and exactly twice as high as the rate recorded in the age group > 70 years (AAPC +0.9%; 95% CI: 0.7 to 1.1 ; p < 0.001). Conclusion: This study reveals substantial disparities in BC incidence and mortality rates, as well as significant differences in clinicopathological and sociodemographic features, among women aged < 40 compared to those in the 40-69 and ≥ 70 years in Brazil. Keywords: Breast cancer; age groups; incidence; mortality. Citation Format: Jesse Lopes da Silva, Andreia Cristina De Melo, Lucas Zanetti de Albuquerque, Mariana Espirito Santo Rodrigues, Luiz Claudio Santos Thuler. Age Group Analysis of Breast Cancer Patterns in Brazil: Findings from Population-Based Registries [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 PO3-09-11.

The Impact of microRNA SNPs on Breast Cancer: Potential Biomarkers for Disease Detection.

Breast cancer is considered a significant health concern worldwide, with genetic predisposition playing a critical role in its etiology. Single nucleotide polymorphisms (SNPs), particularly those within the 3' untranslated regions (3'UTRs) of target genes, are emerging as key factors in breast cancer susceptibility. Specifically, miRNAs have been recognized as possible novel approach for biomarkers discovery for both prognosis and diagnosis due to their direct association with cancer progression. Regional disparities in breast cancer incidence underscore the need for precise interventions, considering socio-cultural and economic factors. This review explores into the differential effects of SNP-miRNA interactions on breast cancer risk, emphasizing both risk-enhancing and protective associations across diverse populations. Furthermore, it explores the clinical implications of these findings, highlighting the potential of personalized approaches in breast cancer management. Additionally, it reviews the evolving therapeutic prospect of microRNAs (miRNAs), extending beyond cancer therapeutics to encompass various diseases, indicative of their versatility as therapeutic agents.

A case-control study of 10,757 individuals to assess potentially modifiable risk factors, including stress, for breast cancer among Chinese patients in Hong Kong.

e22522 Background: Breast cancer is the most common cancer in women worldwide. Both intrinsic and environmental factors contribute to the disparities in breast cancer incidence across different regions. In Hong Kong, the incidence has been increasing in the past decades. With over 4700 women diagnosed in 2019, breast cancer is responsible for 27% of all female cancers in Hong Kong. Apart from intrinsic non-modifiable risk factors, some risk factors are modifiable and may reduce cancer risk. Methods: We conducted a case-control study that involved breast cancer patients from the Hong Kong Breast Cancer Registry with matched healthy controls from the community between 2014 and 2017. A standardized written questionnaire was used through face-to-face interviews of all study participants. The questionnaire collected information on participants’ demographics, general health, smoking history and other lifestyle factors including physical activity, self-assessed dietary habits (balanced, vegetarian, meat and dairy-rich diets), self-perceived stress levels (measured with a 4-point Likert scale, and high stress level was defined as having over 50% of the participant’s time with stress being scored 3 or above out of a Likert scale of 4), body mass index, family history, menstrual and reproductive history, and history on the use of oral contraceptives and hormone replacement therapy. Multiple logistic regression was fitted to compare all risk factors. Results: A total of 5,186 breast cancer patients and 5,571 controls were recruited. Modifiable risk factors that were shown to be associated with an increased risk of breast cancer included self-perceived high stress level (adjusted odd ratios [aOR] = 3.44; 95% CI = 3.13-3.78), meat-rich diet (aOR = 1.77; 95% CI = 1.54-2.04), dairy-rich diet (aOR = 3.33; 95% CI = 2.01-5.52), overweight/obese status (aOR = 1.21; 95% CI = 1.10-1.32), delayed child-bearing (aOR = 2.23; 95% CI = 1.79-2.79), nulliparity (aOR = 1.21; 95% CI = 1.08-1.35) and ever use of oral contraceptives (aOR = 1.34; 95% CI = 1.22-1.47), while exercise (OR = 0.62; 95% CI = 0.56-0.68) and breast-feeding (aOR = 0.76; 95% CI = 0.69-0.83) were associated with reduced risk. Conclusions: In Hong Kong, high stress level, meat- and dairy- rich diet, overweight/obese, reproductive history and use of oral contraceptives were identified to be modifiable risk factors for breast cancer. Adjusting these factors through lifestyle modification may curb the increasing trend of breast cancer incidences in the coming decades.

The Impact of Socioeconomic Status and Social Determinants of Health on Disparities in Breast Cancer Incidence, Treatment, and Outcomes

The Impact of Socioeconomic Status and Social Determinants of Health on Disparities in Breast Cancer Incidence, Treatment, and Outcomes

Abstract 474: Integrating imaging and multi-omics data to elucidate racial differences in breast tumor biology to optimize precision oncology approaches and patient outcome

Abstract Background: Racial disparities in breast cancer incidence and clinical outcome have been well characterized. In particular, African American (AA) patients have higher mortality rates than other racial groups. Research into these racial disparities has primarily focused on socioeconomic determinants, with some studies exploring potential molecular determinants and limited biological differences found between AA and Caucasian patient tumors. Tumor intrinsic and extrinsic factors that promote racial differences in breast cancer development and patient outcome are not fully understood and strategies to address this are scarce. As a result, we have developed a platform that combines patient-specific imaging and multi-omics data to elucidate how biological differences integrate to promote racial disparities in tumor behavior and patient outcome. Methods: Imaging and transcriptomic data from over 500 patients were integrated within the SimBioSys TumoScope biophysical modeling software to understand racial differences in tumor biology and coordinated tumor behavior. Results: AA patients have tumors that display higher growth rates, characteristically have higher adipose tissue around the tumor, higher spatial variation in drug secretion, lower spatial variation in blood flow/and increased tumor stiffness. Conclusion: Using a transdisciplinary approach, our results show that metabolic and structural tumor features are associated with the disproportionately poor survival rates observed in AA breast cancer patients. By characterizing racial-specific tumor intrinsic and extrinsic biological factors and their potential interactions, strategies may emerge to personalize clinical management based on racial differences. In this way, precision oncology approaches can be applied to increase life-expectancy for racial minorities with breast cancer. Citation Format: Nicole Liadis, Tyler Earnest, Eduardo Braun, Anu Antony, Lance Munn, Michael Hallock, Daniel Cook, The SimBioSys Team. Integrating imaging and multi-omics data to elucidate racial differences in breast tumor biology to optimize precision oncology approaches and patient outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 474.

Abstract P3-14-06: A transdisciplinary approach for characterizing racial differences in the biology of breast cancer by integrating imaging and -omics data

Abstract Background: Racial disparities in breast cancer incidence and clinical outcome have become increasingly recognized. In particular, African American (AA) patients have higher mortality rates than other racial groups. Research into these racial disparities has primarily focused on socioeconomic determinants, with some studies exploring molecular determinants. Biologically, few differences in genetics or transcriptomics have been found to be due to race. Understanding racial differences in breast cancer development as they relate to patient outcomes requires a comprehensive approach, integrating tumor intrinsic and extrinsic factors. We have developed a platform that combines patient-specific imaging and -omics data to elucidate how biological differences are integrated to cause racial differences in tumor behavior and disparities in patient outcome. Methods: Imaging and transcriptomic data from over 500 patients were integrated within the SimBioSys TumorScope biophysical modeling software to understand how racial differences in tumor biology are coordinated to determine tumor behavior. Specifically, we used artificial intelligence to automatically segment tumors from patient MRIs, and construct 3D models of patient tumors and the surrounding microenvironment. We then used these segmentations to identify radiological differences between AA and Caucasian patients. Simultaneously, we used patient-specific mathematical models of tumor metabolism constructed from RNA-seq data to determine racial differences in tumor metabolism. Results: We profiled structural differences in 266 tumors (181 Caucasian and 85 AA) and metabolic differences in 552 tumors (422 Caucasian and 130 AA). In our patient cohort, AA tumors were smaller (AA/Caucasian volume = 0.573, p = 0.004), more spherical (AA/Caucasian sphericity = 1.12, p = 0.0046), had lower spatial variation in tumor stiffness (AA/Caucasian Contrast GLRLM Gray Level Non-uniformity = 0.63, p = 0.0004), and had higher vascular perfusion than Caucasian tumors (AA/Caucasian vascular shell density = 1.43, p = 0.0015). In addition, AA tumors had increased levels in several features which may contribute to decreased response to therapy, including a higher spatial heterogeneity in drug delivery and secretion (AA/Caucasian WIS std = 2.2, p = 5.9x10-9, WOS std = 11.5, p < 10-10) and higher levels of adipose surrounding the tumor (AA/Caucasian adipose shell density = 1.13, p = 0.0024). Metabolically, we found that tumors from AA patients have increased sphingolipid metabolism (AA/Caucasian fold change (FC) = 1.4, p = 0.04) and pyruvate metabolism (FC = 1.03, p = 0.03); and decreased starch and sucrose metabolism (FC = 0.89, p = 0.03), fatty acid metabolism (average FC = 0.83, p = 0.04), glycerolipid metabolism (FC = 0.70, p = 0.025), and acylglyceride metabolism (FC = 0.69, p = 0.025). Furthermore, we found that these metabolic features integrate in such a way that tumors from AA patients had an increased specific growth rate (FC = 1.52, p = 0.014), compared to Caucasian patients (even when correcting for PAM50 subtype). Conclusion: Taken together, these results indicate that tumors of AA patients have a more aggressive phenotype (high growth rate) and potentially a lower response to chemotherapeutic drugs (high spatial heterogeneity of drug delivery and secretion and high surrounding adipose). These features likely work together to contribute to the disproportionately poor survival rates repeatedly observed in AA breast cancer patients. By characterizing racial-specific tumor intrinsic and extrinsic biological factor and their potential interactions, TumorScope simulation platform can assist in finding strategies that may improve clinical management, life-expectancy, and overall outcomes of racial minorities with breast cancer. Citation Format: Nicole Liadis, Tyler Earnest, Eduardo Bruan, Anu Antony, Michael Hallock, Daniel Cook. A transdisciplinary approach for characterizing racial differences in the biology of breast cancer by integrating imaging and -omics data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-06.

Place Is Power: Investing in Communities as a Systemic Leverage Point to Reduce Breast Cancer Disparities by Race

Racial disparities in breast cancer present a vexing and complex challenge for public health. A diverse array of factors contributes to disparities in breast cancer incidence and outcomes, and, thus far, efforts to improve racial equity have yielded mixed results. Systems theory offers a model that is well-suited to addressing complex issues. In particular, the concept of a systemic leverage point offers a clue that may assist researchers, policymakers, and interventionists in formulating innovative and comprehensive approaches to eliminating racial disparities in breast cancer. Naming systemic racism as a fundamental cause of disparities, we use systems theory to identify residential segregation as a key leverage point and a driver of racial inequities across the social, economic, and environmental determinants of health. We call on researchers, policymakers, and interventionists to use a systems-informed, community-based participatory approach, aimed at harnessing the power of place, to engage directly with community stakeholders in coordinating efforts to prevent breast cancer, and work toward eliminating disparities in communities of color.

Income Disparity in Breast Cancer Incidence and Stage at Presentation: A National Population Study of South Korea.

This study aims to explore income-based disparities in breast cancer (BC) incidence and stage at presentation in a national population in South Korea, where a National Cancer Screening Program (NCSP) has been implemented. In 2007, new patients with BC were identified using the Korea Central Cancer Registry database. We calculated adjusted odds ratios (aORs) to evaluate the association between individual income level and the risk of distant stage BC at presentation, adjusting for women's age, body mass index, disability registration, employment, region of residence, and year of diagnosis. The cumulative age-standardized incidence of BC in the 11 years was highest among women in the richest quintile (2,040 per 100,000 women for 11 years), whereas the proportion of distant stage at presentation was the highest (10.2%) among the medical aid beneficiaries. The aOR of distant stage diagnosis at presentation was higher for lower-income quintiles, and the risk was the highest in the medical aid beneficiaries (aOR, 2.25; 95% confidence interval, 1.97-2.58) than in the richest quintile. The income-based gradient in aORs for distant stage did not differ between younger (< 40 years) and older patients. A higher risk of distant stage BC at presentation among the lower-income and medical aid groups in the context of a NCSP was observed. A more focused approach toward women in lower-income groups is necessary to alleviate the disparity in the risk of advanced BC.

Geographic disparities of breast cancer incidence in Portugal at the district level: A spatial age-period-cohort analysis, 1998-2011

BackgroundBreast cancer is the most common malignancy in women world-wide and the most common cause of cancer deaths, which can often be managed with early diagnosis and subsequent treatment. Here, we focus on geographic disparities in incidence within Portugal for three age groups of women (30−49; 50−69; 70−84 years). MethodsAge-period-cohort (APC) models are widely used in cancer surveillance, and these models have recently been extended to allow spatially-varying effects. We apply novel spatial APC models to estimate relative risk and age-adjusted temporal trends at the district level for the 20 districts in Portugal. Our model allows us to report on country-wide trends, but also to investigate geographic disparities between districts and trends within districts. ResultsAge-adjusted breast cancer incidence was increasing over 1998–2011 for all three age groups and in every district in Portugal. However, we detect spatially-structured between-district heterogeneity in relative risk and age-adjusted trends (Net Drifts) for each of the three age groups, which is most pronounced in the highly-screened (50−69yo) and late-onset (70−84yo) groups of women. ConclusionsWe present evidence of disparities in breast cancer incidence at a more granular geographic level than previously reported. Some disparities may be due to latent risk factors, which cannot be accounted for by age, birth year, and geographic location alone. ImpactOur study motivates resuming data collection for breast cancer incidence at the district level in Portugal, as well as the study of exogenous risk factors.

Real-world quality of life (QoL) in black, indigenous and people of color (BIPOC) treated with palbociclib (PAL) and endocrine therapy for hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): A subgroup analysis from POLARIS.

1071 Background: Racial disparities in breast cancer incidence, mortality, and care are well documented. PAL plus endocrine therapy is indicated for patients (pts) with HR+/HER2− ABC. Findings from the PALOMA clinical trials have shown that pts receiving PAL maintained stable QoL; however, limited QoL data are available from real-world settings for BIPOC receiving PAL. Methods: POLARIS is a noninterventional, prospective, primarily US-based study in pts with HR+/HER2– ABC receiving PAL. QoL was assessed with the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline, monthly for the first 3 mo of treatment (Tx) with PAL, and then every 3 mo. In this interim analysis, we report Tx patterns and QoL assessments at baseline and at 6 mo and 12 mo in BIPOC from POLARIS. Results: Of 1280 pts treated with PAL as November 10, 2020, 233 were included in the BIPOC subgroup of whom 159 (68.2%) completed PAL Tx for ≥6 mo and 112 (48.1%) for ≥12 mo. In the BIPOC cohort, 59.2% of pts were black, 35.2% Hispanic, 3.4% American Indian or Alaskan native, 2.1% Pacific Islander. PAL in combination with letrozole/anastrozole was received by 116 pts, 94 received PAL plus fulvestrant, 13 received PAL plus exemestane, and 10 received PAL plus another Tx; 175 pts (75.1%) received PAL as first-line Tx. Mean EORTC QLQ-C30 global health QoL and functional scales scores remained stable over the first 12 mo of PAL Tx, without any changes at or above the 10-point threshold considered clinically meaningful, and were similar to those previously reported in an earlier analysis of the entire POLARIS population (Table and Rocque et al SABCS 2019). Symptom scales scores, including nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and diarrhea, also remained stable over 12 mo. Conclusions: In this subgroup analysis, PAL had no significant adverse impact on QOL in BIPOC with HR+/HER2– ABC, consistent with previous findings from the total POLARIS study population. Pfizer (NCT03280303). Clinical trial information: NCT03280303 .[Table: see text]

Abstract PS7-67: Breast cancer subtype differences according to race/ethnicity

Abstract Background:Breast cancer incidence and mortality rate differ across racial/ethnic population in the US, little is known about Asian and Pacific Island subpopulations. For the Asian subgroups (Japanese, Chinese, Korean, Filipino, Vietnamese, etc.) in the U.S., overall incidence has increased over recent decades. From 2012-2016 Hawai’i incidence rates were significantly higher than the US overall for breast cancer, although cancer mortality rates in Hawai’i were significantly lower than the US overall for breast cancer. Significant disparities in breast cancer incidence and mortality exist, with Native Hawaiian and Filipino women particularly affected. Native Hawaiian women have the highest incidence and also have a 50% higher risk of breast cancer mortality compared to White women. In addition, there are dramatic racial/ethnic differences in mortality rates in the state, with Native Hawaiians having the highest mortality rates compared to all other major racial/ethnic groups. Methods:We examined unique breast cancer cases in a major health system in Hawai’i from 2013-2019 according to race/ethnicity. We found statically significant differences in breast cancer subtype according to race/ethnicity and menopausal status. Results:In 561 premenopausal breast cancer cases, we found that Native Hawaiians were less likely to have triple negative breast cancer (OR 0.2, p=0.02) and Japanese were less likely to have triple positive breast cancer (OR 0.17, p=0.002) compared to other race/ethnicities. In 1,954 postmenopausal breast cancer cases, we found that Filipino women were more likely to have hormone negative/HER2 positive breast cancer (OR 2.38, p=0.006) compared to other race/ethnicities. Table 1-Breast cancer subtype according to race/ethnicity in premenopausal women Table 2-Breast cancer subtype according to race/ethnicity in postmenopausal women Summary:Although behavioral, environmental, social, economic, and biological factors have been shown to influence risk and survival for breast cancer, they do not entirely explain the differences observed across populations. These findings show the need to characterize the underlying differences in breast tumor biology of breast cancer patients from different racial/ethnic groups to better understand known health disparities. Our hypothesis is that molecular characteristics are key contributors to the disparities in disease outcome across the different racial/ethnic groups. We have previously shown the importance of the tumor microenvironment differences in racial/ethnic groups in our population. Citation Format: Jami Fukui, Surbhi Bansil, Anthony Silva, Jeffrey Killeen, Ian Pagano. Breast cancer subtype differences according to race/ethnicity [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-67.

Abstract PS7-68: Racial disparities within basal-type breast cancer: Clinical and molecular features of African American and Caucasian obese patients

Abstract Background: African American breast cancer patients (AA) are diagnosed at a younger age and present more frequently with triple-negative/Basal tumors than Caucasian American patients (CA). High prevalence of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome in AA may confound attempts to evaluate the influence of race on gene expression. Previously we showed that differentially expressed genes (DEGs) between AA and CA within the Basal subtype were related to metabolism, translation, and cell signaling pathways (Nunes et al. 2019). However, AA had higher obesity and T2DM rates than CA, and we were unable to distinguish between the influence of metabolic factors and race. In the current analysis, we aim to dissect these factors by comparing clinical and molecular features of Basal-type breast tumors in obese AA and CA. Methods: The prospective, observational FLEX Registry (NCT03053193) includes stage I-III breast cancer patients who receive 70-gene signature (MammaPrint, MP)/80-gene signature (BluePrint, BP) testing and consent to full transcriptome and clinical data collection. This interim substudy included 50 AA and 96 CA (n=146), enrolled from 2017 to present, all obese by body mass index (BMI, ≥30) and whose tumors were MP High Risk and BP Basal subtype. AA were significantly younger (mean, 55 years) than CA (mean, 60 years, p=0.02); thus, an age distribution-matched subset (n=49 AA, n=49 CA) was added for comparison. Gene expression data were quantile normalized using R limma package; DEGs were compared between groups in the following: (1) all AA (n=50) and CA (n=96), (2) AA and 3 random selections of CA (n=50 pairs), and (3) age-matched AA and CA (n=49 pairs). Results: Clinical factors, including tumor stage, nodal stage, and T2DM status were similar between AA and CA, regardless of age-matching. Most tumors were T1/2 (83% AA, 88% CA) and negative for nodal involvement (77% AA, 68% CA). 94% of tumors from AA and 74% of tumors from CA were grade 3 (p=0.17). Notably, 32% of tumors from AA and 46% of tumors from CA were ER+ by immunohistochemistry. Age-matched AA and CA had a 20% rate of T2DM. 152 DEGs were significant (adjusted p&amp;lt;0.05) in at least one comparison, with 115 genes more highly expressed in AA and 37 genes more highly expressed in CA. Across all comparisons, 6 genes were consistently more highly expressed in AA: PSPH, NOTCH2NL, POLR1A, AC069240.1, ORAI1, and RPS26P10. Except ORAI1, these genes were also found in the previous comparison between Basal-type AA and CA, and the current analysis confirmed 11/16 DEGs previously reported (Nunes et al. 2019). Genes more highly expressed in AA are associated with transcription, angiogenesis, and Notch signaling pathways, as well as breast cancer aggressiveness and treatment resistance. Conclusions: Higher prevalence of obesity/T2DM in AA has been proposed as a key factor to explain racial disparities in breast cancer incidence and prognosis, but the current results suggest that race may influence DEGs more than differences in tumor subtype, age, or metabolic factors. This comparison also emphasizes the importance of matched clinical features for DEG analysis and suggests disparities in AA beyond those attributable to clinical differences within the population. DEGs in AA suggest upregulation of Notch-associated aggressiveness, which may be particularly relevant under hypoxic conditions (e.g., obesity), and pathways associated with stemness, metastasis, and chemotherapy resistance. Notch pathway also interacts with key oncogenic pathways, and future studies will reveal the molecular networks underlying racial disparity in AA and CA breast cancer patients. Citation Format: Dipali Sharma, Lisa E. Blumencranz, Heather M. Kling, Sahra Uygun, Sarah Untch, William Audeh, Jennifer A. Crozier, Mehran Habibi, Raquel Nunes. Racial disparities within basal-type breast cancer: Clinical and molecular features of African American and Caucasian obese patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-68.

Abstract 4636: Breast cancer age-specific incidence rates among Ghanaian women by breast cancer risk factors: A study using census and population-based case-control study data

Abstract Introduction: Although breast cancer incidence in sub-Saharan African countries, including Ghana, has been historically low, incidence is rising. Evaluating age-specific incidence rates by breast cancer risk factors may provide etiologic insights. Here we present age-specific incidence rates for breast cancer estimated from the Ghana Breast Health Study (GBHS) for key breast cancer risk factors. Methods: GBHS is a population-based case-control study with 1,071 pathologically confirmed incident invasive breast cancer cases (18-74 years old) diagnosed between 2013-2015 in three hospitals in Accra and Kumasi. A total of 2,094 controls were sampled from the population, and frequency matched by site and age to the cases. Sample weights for controls were calculated using data from the 2010 Ghana Census, adjusted for non-response. Data on incident breast cancer cases in Accra (2012-2014) and Kumasi (2013-2015) were obtained from their respective cancer registries and compared to the incidence rates observed in the GBHS. Using data from GBHS adjusted by sampling weights, we estimated 5-year age-specific breast cancer incidence rates and 95% confidence intervals overall and according to breast cancer risk factors. Results: Age-specific breast cancer incidence rates estimated from the GBHS rose quickly until approximately age 50 when the rate plateaued but still rose (Clemmeson's hook), which was consistent with cancer registry data from Kumasi and Accra. The rates from the GBHS are not significantly different from the cancer registry rates under age 50 but are significantly higher after age 50. While the rates from the GBHS and Accra and Kumasi cancer registries were much lower than rates observed in the SEER registries for African American women, the trends were consistent. Analyses of overall rates by breast cancer risk factors showed that age-specific breast cancer risk was elevated among women with a family history of breast cancer across all ages. Data suggested cross-over interactions for other factors, particularly parity, and breastfeeding among parous women. Specifically, incidence rates were higher for parous than nulliparous women aged 20-35 years, while incidence rates were lower for parous and breastfeeding (among parous) women older than 35 years. Conclusions: Age-specific incidence rates of breast cancer that demonstrate cross-over interactions by risk factors may be important in understanding racial disparities in breast cancer incidence, overall as well as for specific breast cancer subtypes. Elevated risk among young parous women may be indicative of the higher risk associated with early-onset (triple-negative) breast cancer. Citation Format: Brittny Davis Lynn, Jonine Figueroa, Richard Biritwum, Beatrice Wiafe Addai, Baffour Awuah, Joe Net Clegg-Lamptey, Robertson Adjei, Lucy Afriyie, Joel Yarney, Naomi Oyoe Ohene Oti, Daniel Ansong, Seth Wiafe, Louise Brinton, Montserrat Garcia-Closas, Barry Graubard. Breast cancer age-specific incidence rates among Ghanaian women by breast cancer risk factors: A study using census and population-based case-control study data [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4636.

Abstract C081: Results from a cross-sector collaboration: Understanding contributors to breast and lung cancer disparities and creating novel approaches to reduce impact

Abstract Background: Advances in prevention, detection, and treatment of breast and lung cancer have decreased incidence and mortality rates but have not benefited all populations equally. In Wisconsin, the disparity in lung cancer mortality rates between Black and White residents is the second largest in the nation, and disparities in breast cancer incidence have significantly worsened in the past decade. To address the complex etiology behind these disparities, the Advancing a Healthier Wisconsin Endowment assembled a racially and ethnically diverse multidisciplinary team to inform efforts to reduce cancer disparities in Wisconsin. Methods: Our panel of eight experts, along with a program facilitator, met biweekly for 15 months. Members had broad expertise in diverse communities, public health, behavioral science, health geography, molecular biology and clinical care. The team had not previously collaborated together. The team's objectives were to (1) gain a contextualized understanding of the molecular, genetic, socioeconomic, and behavioral factors contributing to cancer disparities, as well as barriers and promoters to these discoveries; (2) identify relevant issues on which to focus future efforts; and (3) facilitate the creation of collaborative work groups to develop and implement innovative strategies to address cancer disparities statewide. Results: At the conclusion, team efforts included: (1) creating statewide maps reflecting breast and lung cancer incidence, late-stage diagnosis, and mortality, as well as potential socioeconomic contributors to disparities; (2) reviewing literature on efforts reducing cancer disparities; (3) completing a root cause analysis of cultural, socioeconomic, and genetic contributors; (4) identifying and assessing focused topics for further study; and (5) designing a comprehensive framework to guide the work of collaborative, cross-sector teams on prioritized topics. An additional and notable result was feedback from team members that participation in the group challenged them to reimagine cross-disciplinary collaboration and consider how to engage diverse backgrounds and perspectives in future cancer-disparities work. Conclusions and Future Directions: The resulting topics and framework will direct the funding and formation of collaborative, cross-sector work groups to (1) think beyond their expertise; (2) create, adapt, or adopt collaborative strategies for addressing complex health problems; and (3) develop, test, and evaluate initiatives to address breast and lung cancer disparities in incidence, late-stage diagnosis, and mortality. Citation Format: Melinda R. Stolley, Tobi Anne Cawthra, Jessica Olson, Sandra Millon-Underwood, Kirsten Beyer, David Fraser, Lyle Ignace, Laura Pinsoneault, Jose Salazar, Alonzo Walker, Carol Williams, Cheryl Maurana. Results from a cross-sector collaboration: Understanding contributors to breast and lung cancer disparities and creating novel approaches to reduce impact [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C081.

Quantification of inequities in breast cancer incidence in New Mexico through Bayesian disease mapping.

e13617 Background: Breast cancer (BC) is the most prevalent cancer of women in the United States (US). The incidence rates for BC among American Indian and Alaska Native (AI/AN) women vary across the US. A novel application of Bayesian disease mapping was applied to quantify potential inequities in 10-year BC incidence in New Mexico (NM) in order to better inform health equity initiatives within the AI/AN at-risk population. Methods: Surveillance, Epidemiology, and End Results Program (SEER) data from 2005 to 2014 were used to identify new cases of BC within the 33 counties in NM. Initially, a Poisson-gamma model was applied to quantify the reduction in risk of BC within the at-risk AI/AN population compared with the general at-risk population. To account for spatial variation and to address the small area estimation problem inherent in these data by borrowing strength globally and locally in NM, we applied Bayesian disease mapping to the counts of county-level BC cases. We quantified the disparity effect, as measured by the rate ratio (95% credible interval [CI]), comparing the incidence of BC between at-risk AI/AN and non-AI/AN women, and assessed if the rate ratio differed between counties. Markov chain Monte Carlo sampling was used to estimate posterior quantities and the deviance information criterion was used for model selection. Results: In 2010, 1,041,758 women were at-risk for BC of which 107,656 (10.3%) were AI/AN women. During the 10-year study period, 12,974 new BC cases were recorded in the general at-risk population. In the at-risk AI/AN population, the expected number of new cases during the 10-year study period, therefore, was 1,340.74; however, 597 incidence cases of BC were diagnosed in the at-risk AI/AN population resulting in a posterior mean for the true relative risk of 0.445 (95% CI: 0.410, 0.482). Based on the selected model that accounted for over dispersion and spatial correlation among the 33 counties, the posterior mean of the overall adjusted rate ratio was 0.405 (95% CI: 0.336, 0.478). The adjusted rate of BC in AI/AN women was 0.40 times the corresponding adjusted rate for women who were non-AI/AN. Further, the adjusted rate ratios were similar for each county. Conclusions: The novel application of Bayesian disease mapping to these data provided substantial evidence of a significant overall disparity effect in BC incidence within NM between at-risk AI/AN and non-AI/AN women, which was more marked than previous reports. Targeted state-wide health equity initiatives may lead to reducing disparities in BC incidence in AI/AN at-risk women.

Contribution of socioeconomic and environmental factors to geographic disparities in breast cancer risk in the Nurses' Health Study II.

Background:Evidence of geographic disparities in breast cancer incidence within the United States and spatial analyses can provide insight into the potential contribution of environmental exposures or other geographically varying factors to these disparities.Methods:We applied generalized additive models to smooth geocoded residential coordinates while adjusting for covariates. Our analysis included 3,478 breast cancer cases among 24,519 control women from the Nurses’ Health Study II. We first examined associations with residential location during adolescence (high school address) or early adulthood (address in 1991). We then assessed the contribution from known individual-level risk factors, measures of socioeconomic status, and occupational and environmental factors that vary spatially and have been linked to breast cancer. Secondary analyses by estrogen receptor and menopausal status were also conducted.Results:We identified geographic patterns of breast cancer risk associated with location during adolescence, with increased risk apparent in Michigan, the Northwest, and the New York City area, that shifted to southern New England when addresses during early adulthood were analyzed. Similar results were observed after adjustment for individual- and area-level factors, although spatial associations were no longer statistically significant.Conclusions:Breast cancer risk is not spatially uniform across the United States, and incidence patterns varied depending on the timing during life of the residence considered. Geographic disparities persisted even after accounting for established and suspected breast cancer risk factors, suggesting that unmeasured environmental or lifestyle risk factors may explain geographic variation in risk in different parts of the country.

Differences in Genome-wide DNA Methylation Profiles in Breast Milk by Race and Lactation Duration.

Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a woman's risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples and demographic, behavioral, and reproductive data, were obtained from cancer-free, uniparous, and lactating U.S. black (n = 57) and white (n = 82) women, ages 19-44. Genome-wide DNA methylation analysis was performed on extracted breast milk DNA using the Infinium HumanMethylation450 BeadChip. Statistically significant associations between breast cancer risk factors and DNA methylation beta values, adjusting for potential confounders, were determined using linear regression followed by Bonferroni Correction (P < 1.63 × 10-7). Epigenetic analysis in breast milk revealed statistically significant associations with race and lactation duration. Of the 284 CpG sites associated with race, 242 were hypermethylated in black women. All 227 CpG sites associated with lactation duration were hypomethylated in women who lactated longer. Ingenuity Pathway Analysis of differentially methylated promoter region CpGs by race and lactation duration revealed enrichment for networks implicated in carcinogenesis. Associations between DNA methylation and lactation duration may offer insight on its role in lowering breast cancer risk. Epigenetic associations with race may mediate social, behavioral, or other factors related to breast cancer and may provide insight into potential mechanisms underlying racial disparities in breast cancer incidence.

Abstract IA03: Breast cancer disparities: Progress, challenges, and opportunities

Abstract Breast cancer remains the most commonly diagnosed cancer among women in the United States and worldwide. Important disparities in breast cancer incidence and mortality persist. African American, Hispanic, and American Indian/Alaska Native women are more commonly diagnosed with aggressive forms of breast cancer (including advanced stage disease and triple-negative breast cancer) and experience lower 5-year survival rates. While survival rates have improved across all races/ethnicities, the disparity gap between different races/ethnicities has held essentially constant. Underlying these disparities are a host of factors related to access to care, socioeconomic status, lifestyle/cultural factors, and systems-level factors. For example, mammography utilization varies considerably by education and insurance status, and African American and Hispanic women are less like to receive guideline-concordant treatment for their breast cancers compared to non-Hispanic whites. Additionally, several risk factors that are more common among African American and Hispanic women (including parity, early age at first pregnancy, and obesity) have been shown to be associated with risk of triple-negative breast cancer, potentially accounting for the greater frequency of this aggressive subtype that they experience. Contributors to breast cancer disparities occur on multiple levels and span the entire breast cancer continuum from prevention to screening to diagnosis/treatment and to survivorship. Continued research on all fronts is necessary to address these persistent disparities. Citation Format: Christopher I. Li. Breast cancer disparities: Progress, challenges, and opportunities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA03.

Abstract P6-10-07: Differences in genome-wide DNA methylation levels in breast milk by race and lactation duration

Abstract Introduction: Identifying biomarkers of breast cancer risk among young women would have value in developing effective screening and prevention strategies at early ages. We have proposed that DNA methylation analysis of breast milk may provide breast cancer risk information among young women, and could possibly provide etiologic clues related to the higher rates of early onset cancers among African American as compared with White women in the US. Objective: The purpose of this project was to identify associations between genome-wide DNA methylation levels in breast milk and race adjusted for other breast cancer risk factors. Study Population: Cancer-free, lactating U.S. Black (n=57) and White (n=82) women, ages 19 to 44, provided frozen breast milk samples, as well as demographic, behavioral, and reproductive data, to the Breastmilk Laboratory at University of Massachusetts Amherst. Women were uniparous and did not have a personal history of breast cancer at the time of milk donation. Methods: DNA was extracted from breast milk samples using the phenol-chloroform method. Genome-wide methylation analysis was performed on breast milk samples using the Infinium HumanMethylation450 BeadChip. Probes with 50% or more missing data, cross-reactive probes, as well as probes with minor allelic frequency greater than 0.05 in European- or African-Americans were removed, leaving 379,042 CpG sites for analysis. Multivariate generalized linear regression models were used to examine associations between race and other breast cancer risk factors and methylation beta values, adjusting for potential confounding factors. P-values less than 1E-7 were considered statistically significant. Results: Black women in this study were more likely to be never smokers, to not have used over-the-counter pain medication in the past week, and to breastfeed longer. After adjustment by age, BMI, smoking status, and batch number, race was significantly associated with differential methylation at 1143 CpG sites, including 1024 at which Black women demonstrated increased methylation levels. Additionally, breastfeeding duration was associated with 269 CpG sites, with 268 showing a significant inverse relationship with methylation. Methylation sites significantly associated with Black race and lactation duration were located within tumor suppressor and promoter genes as well as in genes implicated in obesity and diabetes. Conclusion: This preliminarily analysis of DNA methylation in breast milk suggests that Black women have increased methylation and longer breastfeeding is associated with reduced methylation. Further research to understand how etiologic factors related to breast cancer may alter DNA methylation patterns in normal breast may lead to improved understanding of breast cancer risk at a young age and potentially causes of racial disparities in breast cancer incidence between White and Black women. Citation Format: Davis Lynn BC, Bodelon C, Pfeiffer RM, Yang HP, Yang H, Lee M, Laird PW, Campan M, Weisenberger DJ, Murphy J, Sherman ME, Browne EP, Anderton DL, Arcaro KF, Gierach GL. Differences in genome-wide DNA methylation levels in breast milk by race and lactation duration [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-10-07.

Racial/Ethnic Disparities in Breast Cancer Incidence, Risk Factors, Health Care Utilization, and Outcomes in the USA

Purpose of the Review This review examines racial/ethnic disparities in female breast cancer within the USA. Specifically, differences in breast cancer incidence, risk factors, health care utilization use, and outcomes among Caucasians and non-Caucasians are explored.