Breast Cancer Continuum Research Articles

Tumor-on-chip platforms for breast cancer continuum concept modeling.

Our previous article entitled "Proteomics and its applications in breast cancer", proposed a Breast Cancer Continuum Concept (BCCC), including a Breast Cancer Cell Continuum Concept as well as a Breast Cancer Proteomic Continuum Concept. Breast cancer-on-chip (BCoC), breast cancer liquid biopsy-on-chip (BCLBoC), and breast cancer metastasis-on-chip (BCMoC) models successfully recapitulate and reproduce in vitro the principal mechanisms and events involved in BCCC. Thus, BCoC, BCLBoC, and BCMoC platforms allow for multiple cell lines co-cultivation to reproduce BC hallmark features, recapitulating cell proliferation, cell-to-cell communication, BC cell-stromal crosstalk and stromal activation, effects of local microenvironmental conditions on BC progression, invasion/epithelial-mesenchymal transition (EMT)/migration, intravasation, dissemination through blood and lymphatic circulation, extravasation, distant tissues colonization, and immune escape of cancer cells. Moreover, tumor-on-chip platforms are used for studying the efficacy and toxicity of chemotherapeutic drugs/nano-drugs or nutraceuticals. Therefore, the aim of this review is to summarize and analyse the main bio-medical roles of on-chip platforms that can be used as powerful tools to study the metastatic cascade in BC. As future direction, integration of tumor-on-chip platforms and proteomics-based specific approaches can offer important cues about molecular profile of the metastatic cascade, alowing for novel biomarker discovery. Novel microfluidics-based platforms integrating specific proteomic landscape of human milk, urine, and saliva could be useful for early and non-invasive BC detection. Also, risk-on-chip models may improve BC risk assessment and prevention based on the identification of biomarkers of risk. Moreover, multi-organ-on-chip systems integrating patient-derived BC cells and patient-derived scaffolds have a great potential to study BC at integrative level, due to the systemic nature of BC, for personalized and precision medicine. We also emphasized the strengths and weaknesses of BCoC and BCMoC platforms.

Summary and Roadmap of Breast Cancer Research in the Veterans Affairs.

Women are the largest growing population of Veterans within the U.S. Department of Veterans Affairs (VA) Health Care System. Among women Veterans, breast cancer is the most common malignancy (30% of all cancers), yet little is known about the unique needs of women Veterans with cancer and how to provide them with high quality care. The VA health care system has initiated multiple system-wide systemic efforts, including launching the Breast and Gynecologic Cancer System of Excellence (BGSOE) to address this knowledge gap. This report summarizes the outcomes of the inaugural 2023 VA Women's Cancer Research Conference, which assembled 37 multidisciplinary clinicians, scientists, the VA and civilian partners with a shared goal of advancing VA breast cancer research. Conference objectives were to build a collective vision for improving: (1) referral patterns for breast cancer treatment and patient-level outcomes and (2) molecular and genetic testing patterns across the breast cancer continuum among women Veterans. The meeting hosted 15 speakers at the Houston VA Medical Center. Future research priorities for women Veterans with cancer were identified from discussions and a post-conference survey. We then administered a 13-question post-conference survey to conference attendees. Respondents ranked the research priorities. The survey results show that the cross-cutting cancer research priorities designed to transform cancer care for women Veterans at the VA fit into 5 broad areas of study, including (1) care quality for treatment, (2) improving treatment, (3) care quality of molecular and genetic testing, (4) risk reduction through risk assessment and germline genetic testing, and (5) establishing strategic partnerships. Our data elucidate areas for further investigation to improve the delivery of cancer care.

Abstract PO4-11-02: Accelerating Progress and Achieving Health Equity: The American Cancer Society National Breast Cancer Roundtable

Abstract Background: Breast cancer continues to be a leading cause of death among women, with disparities in mortality rates persisting, particularly for Black women and under-supported communities. In response to this urgent need, the American Cancer Society (ACS) has launched the American Cancer Society National Breast Cancer Roundtable (ACS NBCRT) to address complex challenges across the breast cancer continuum and improve access to quality care. Methods: The ACS NBCRT is a coalition of organizations committed to eliminating disparities and reducing mortality rates. By leveraging strategic partnerships and using the Collective Impact Model, the ACS NBCRT aims to ensure equitable access to screening, treatment, and comprehensive support services. The roundtable follows the proven ACS Roundtable Model, which brings together diverse contributors to drive progress on breast cancer priorities. Results: The ACS NBCRT, chaired by prominent leaders in the field, has engaged thought leaders, organizations, policymakers, and individuals with lived experiences to identify initial roundtable priorities through a community-informed process. The ACS NBCRT conducted three listening sessions, 8 focus groups, 10 community conversations, and 33 informant interviews and received 700+ responses to a nationwide survey. As a result of this work, the ACS NBCRT leadership was able to interpret the data to inform our roundtable's strategic priorities focused on risk reduction, screening, early detection, access to treatment, clinical trials, and support services. Workgroups will address cross-cutting approaches, including health equity, patient navigation, and education, to develop short- and long-term goals for the roundtable. This approach to addressing health equity through our priority areas is intentional, and it is reflected in our engagement with lived experience experts and diverse community contributors in our early planning, formative research, leadership recruitment, and our member engagement and recruitment. Conclusion: Through its Collective Impact approach, the ACS NBCRT is poised and positioned to accelerate progress, promote health equity, and reduce the burden of breast cancer. The roundtable is uniquely designed to identify and addresses gaps by providing a neutral platform to convene diverse stakeholders to establish national priorities across the cancer continuum, catalyze policy and patient care solutions, promote evidence-based strategies and translate them into practice, and leverage volunteer knowledge and experiences to inform the reduction of health disparities. The roundtable's commitment to strategic partnerships, evidence-based strategies, and health equity will drive change and allow the ACS NBCRT to lead the national dialogue on breast cancer. Implications: The establishment of the ACS NBCRT signifies a crucial step towards achieving health equity in breast cancer care. By addressing disparities and promoting collaborative solutions, the roundtable aims to improve outcomes for all people facing breast cancer. Citation Format: Ashley Dedmon, Theresa Petee, Olufunmilayo Olopade, John Williams, Arif Kamal, Sarah Shafir. Accelerating Progress and Achieving Health Equity: The American Cancer Society National Breast Cancer Roundtable [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 PO4-11-02.

Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.

The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease. Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups. Mean V̇O2peak was 2.78 ml O2.kg-1·min-1 (95% confidence interval [CI], -3.94, -1.62 mL O2.kg-1·min-1; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics. Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.

Social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in newly diagnosed women with breast cancer.

Identifying correlates of physical activity and sedentary behaviour allows for the identification of factors that may be targeted in future behaviour change interventions. This study sought to determine the social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in individuals recently diagnosed with breast cancer. Data were collected from 1381 participants within 90 days of diagnosis in the Alberta Moving Beyond Breast Cancer (AMBER) Cohort Study. Physical activity and sedentary behaviour were measured with ActiGraph GT3X+® and activPALTM devices, respectively, for seven consecutive days. Correlates were collected via a self-reported questionnaire, medical record extraction, or measured by staff. Multivariable models were fitted for sedentary behaviour, light physical activity, and moderate-to-vigorous physical activity. Greater sedentary behaviour was associated with higher body fat percentage (BF%) (ß=0.044; p<0.001) and being single (ß=0.542; p<0.002). Lower light physical activity was associated with higher BF% (ß=-0.044; p<0.001), higher body mass index (ß=-0.039; p<0.001), greater disease barrier influence (ß=-0.006; p<0.001), a HER2-positive diagnosis (ß=-0.278; p=0.001), and being single (ß=-0.385; p= 0.001). Lower moderate-to-vigorous physical activity was associated with higher BF% (ß =-0.011; p=0.001), greater disease barrier influence (ß=-0.002; p<0.001), and being of Asian (ß=-0.189; p=0.002) or Indian/South American (ß=-0.189; p=0.002) descent. Greater moderate-to-vigorous physical activity was associated with having greater intentions (ß=0.049; p=0.033) and planning (ß=0.026; p=0.015) towards physical activity. Tailoring interventions to increase physical activity for individuals recently diagnosed with breast cancer may improve long-term outcomes across the breast cancer continuum.

MHealth Interventions to Improve the Breast Cancer Continuum of Care from Prevention to Survivorship of Hispanic Women: A Scoping Review.

Breast cancer is the leading cause of cancer mortality in Hispanic women in the USA. Current interventions to improve breast cancer care include the use of mHealth, but its application in Hispanic women is limited. This scoping review aimed to describe the extent of research literature on the use of mHealth throughout the breast cancer care continuum (prevention, early detection, and treatment) in Hispanic women. A scoping review guided by the Arksey and O'Malley methodological framework and the Joanna Briggs Institute scoping review reporting protocol. Literature search of peer-reviewed research articles from 2012 to 2022 in PubMed, Scopus, and CINAHL® was conducted in March and June 2022. Of the 10 articles selected, seven included Hispanic breast cancer survivors and three included Hispanic women at risk for developing breast cancer. Seven articles involved mobile applications and three articles used text messaging and/or cell phone voicemail. Overall, the use of mHealth for breast cancer care in Hispanics was favorable but generalizability was limited given the type of design and small samples. All interventions were tailored to Hispanic culture. Scarcity of research on mHealth in Hispanic breast cancer care highlights healthcare disparities in this population. Evidence from this review suggests the use of mHealth to be beneficial to improving breast cancer care in Hispanics, but more research is needed involving randomized clinical trials and larger samples.

Role of Secreted Frizzled-Related Protein 1 in Early Breast Carcinogenesis and Breast Cancer Aggressiveness

A human transcriptome array on ERα-positive breast cancer continuum of risk identified Secreted Frizzled-Related Protein 1 (SFRP1) as decreased during breast cancer progression. In addition, SFRP1 was inversely associated with breast tissue age-related lobular involution, and differentially regulated in women with regard to their parity status and the presence of microcalcifications. The causal role of SFRP1 in breast carcinogenesis remains, nevertheless, not well understood. In this study, we characterized mammary epithelial cells from both nulliparous and multiparous mice in organoid culture ex vivo, in the presence of estradiol (E2) and/or hydroxyapatite microcalcifications (HA). Furthermore, we have modulated SFRP1 expression in breast cancer cell lines, including the MCF10A series, and investigated their tumoral properties. We observed that organoids obtained from multiparous mice were resistant to E2 treatment, while organoids obtained from nulliparous mice developed the luminal phenotype associated with a lower ratio between Sfrp1 and Esr1 expression. The decrease in SFRP1 expression in MCF10A and MCF10AT1 cell lines increased their tumorigenic properties in vitro. On the other hand, the overexpression of SFRP1 in MCF10DCIS, MCF10CA1a, and MCF7 reduced their aggressiveness. Our results support the hypothesis that a lack of SFRP1 could have a causal role in early breast carcinogenesis.

Abstract PL03-02: When to intervene along the breast cancer continuum?

Abstract Advances in epidemiology and cancer biology have clearly established that the group of diseases currently deemed “cancers” in fact encompasses many conditions with enormous variation in biologic behavior. Decades of cancer screening have preferentially diagnosed early, asymptomatic, indolent lesions. This trend will only increase as screening technologies become ever more sensitive, leading to an epidemic of overtreatment in completely asymptomatic individuals. The treatment of many of these conditions often has uncertain benefit on cancer mortality, while coming at the clear cost of treatment-related morbidity. Multi-omic testing plays a role in refining treatment recommendations based upon risk of progression. Genomic profiling of accurately annotated longitudinal case control datasets have provided insights into breast lesions termed “ductal carcinoma in situ” (DCIS), which are thought to be precursors to invasion and metastases. Both transcriptomics as well spatially resolved proteomic characterization of DCIS have uncovered novel biology of the epithelial cells that make up DCIS, as well as the heterogeneous precancer ecosystems which can be either permissive or inhibitory for invasion. Recent work has uncovered a clonal evolution pathway characterized by multiclonal invasion, and has helped to build risk stratification tools to refine treatment recommendations. In addition to molecular characterization, risk modeling may yield insights about which patients derive greatest benefit from intervention. For asymptomatic tumors at low risk of cancer progression, there may be little to no benefit to treatment, whereas for more high-risk lesions, progression to invasion and metastasis may be rapid and deadly. Given the lead-time between the development of precancer and progression to invasive disease, there may also be a case for tailoring intervention of screen detected cancer by age and the presence of competing comorbidities. The decision of whether and when to intervene for screen-detected cancers will require a multidisciplinary effort including expertise in cancer biology, mathematical modeling, psychology, health policy, decision science and communication, as well as thoughtful engagement from patients and health care providers to identify the optimal time to intervene along the cancer progression continuum. Citation Format: E. Shelley Hwang. When to intervene along the breast cancer continuum?. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-02.

DNA methylation accelerated age as captured by epigenetic clocks influences breast cancer risk.

Breast cancer continues to be the leading form of cancer among women in the United States. Additionally, disparities across the breast cancer continuum continue to increase for women of historically marginalized populations. The mechanism driving these trends are unclear, however, accelerated biological age may provide key insights into better understanding these disease patterns. Accelerated age measured by DNA methylation using epigenetic clocks is to date the most robust method for estimating accelerated age. Here we synthesize the existing evidence on epigenetic clocks measurement of DNA methylation based accelerated age and breast cancer outcomes. Our database searches were conducted from January 2022 to April 2022 and yielded a total of 2,908 articles for consideration. We implemented methods derived from guidance of the PROSPERO Scoping Review Protocol to assess articles in the PubMed database on epigenetic clocks and breast cancer risk. Five articles were deemed appropriate for inclusion in this review. Ten epigenetic clocks were used across the five articles demonstrating statistically significant results for breast cancer risk. DNA methylation accelerated age varied by sample type. The studies did not consider social factors or epidemiological risk factors. The studies lacked representation of ancestrally diverse populations. DNA methylation based accelerated age as captured by epigenetic clocks has a statistically significant associative relationship with breast cancer risk, however, important social factors that contribute to patterns of methylation were not comprehensively considered in the available literature. More research is needed on DNA methylation based accelerated age across the lifespan including during menopausal transition and in diverse populations. This review demonstrates that DNA methylation accelerated age may provide key insights for tackling increasing rates of U.S. breast cancer incidence and overall disease disparities experienced by women from minoritized backgrounds.

Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer.

Simple SummaryCancer is a complex disease where cells grow and divide in an uncontrolled manner. It is well established that its development and progression involve major alterations in the activity of mitotic regulators. In order to improve our understanding of the contribution of cell-cycle progression defects to the development of disease, the aim of this study is to identify genes relevant to the proper progression of mitosis that are deregulated in breast cancer. Our findings identified CKAP2 as an important mitotic regulator in BC tumors. Moreover, in vitro experiments showed that gene silencing of CKAP2 blocked cell growth, cell migration, and formation of cell aggregates. These results demonstrated the important role of CKAP2 in breast cancer tumor formation.Loss of mitotic regulation is commonly observed in cancer and is a major cause of whole-chromosome aneuploidy. The identification of genes that play a role in the proper progression of mitosis can help us to understand the development and evolution of this disease. Here, we generated a list of proteins implicated in mitosis that we used to probe a patient-derived breast cancer (BC) continuum gene-expression dataset generated by our group by human transcriptome analysis of breast lesions of varying aggressiveness (from normal to invasive). We identified cytoskeleton-associated protein 2 (CKAP2) as an important mitotic regulator in invasive BC. The results showed that CKAP2 is overexpressed in invasive BC tumors when compared with normal tissues, and highly expressed in all BC subtypes. Higher expression of CKAP2 is also related to a worse prognosis in overall survival and relapse-free survival in estrogen receptor (ER)-positive and human epidermal growth factor receptor type 2 (HER2)-negative BC patients. Knockdown of CKAP2 in SKBR3 cells impaired cell proliferation and cell migration and reduced aggregate formation in a 3D culture. Our results show the important role of CKAP2 in BC tumorigenesis, and its potential utility as a prognostic marker in BC.

Tailoring the Evidence for Exercise Oncology within Breast Cancer Care.

Exercise is safe and effective for those living with and beyond breast cancer, with evidence supporting exercise guidelines, and position statements from international organizations. Despite the clearly recognized benefits of exercise for these individuals, many do not participate or maintain recommended exercise levels throughout the breast cancer continuum, highlighting the lack of translation from research into practice. In addition, discerning how exercise can be tailored to address breast cancer-related impairments, so that individuals are able to participate safely and effectively, has also not been studied extensively. Thus, we propose that implementing exercise screening, triage, and referral pathways across the breast cancer continuum may allow for increased accessibility and adoption among those living with and beyond breast cancer. This paper provides an overview of exercise prescription tailoring for common breast cancer and treatment-related impairments, proposes a simplified screening tool for identifying physical activity and movement-related impairments, and considers how best to channel evidence into practice via proposed implementation pathways that may better connect individuals living with and beyond breast cancer with exercise oncology resources through screening, triage, and referral.

Rural Cancer Disparities: Understanding Implications for Breast and Cervical Cancer Diagnoses.

Rural populations experience several disparities, influenced by structural-, community-, and individual-level barriers, across the breast and cervical cancer continuum. This study seeks to identify structural-, community-, and individual-level barriers that affect rural populations across the cancer continuum, understand the role of nurses serving rural populations in breast and cervical cancer screening and diagnostics, and provide recommendations for working with rural patients. This is a secondary analysis of qualitative interviews conducted with public health nurses serving rural populations. Emergent themes indicate that rural populations experience barriers that affect disparities across the breast and cervical cancer continuum, including a changing healthcare landscape, access to cancer-focused care, access to insurance, collective poverty, and demographic factors. Nurses working with rural communities can address these disparities as they fulfill multiple roles and responsibilities.

Implementation of breast cancer continuum of care in low- and middle-income countries during theCOVID-19 pandemic.

Breast cancer is the most common malignancy among women worldwide. The current COVID-19 pandemic represents an unprecedented challenge leading to care disruption, which is more severe in low- and middle-income countries (LMIC) due to existing economic obstacles. This review presents the global perspective and preparedness plans for breast cancer continuum of care amid the COVID-19 outbreak and discusses challenges faced by LMIC in implementing these strategies. Prioritization and triage of breast cancer patients in a multidisciplinary team setting are of paramount importance. Deescalation of systemic and radiation therapy can be utilized safely in selected clinical scenarios. The presence of a framework and resource-adapted recommendations exploiting available evidence-based data with judicious personalized use of current resources is essential for breast cancer care in LMIC during the COVID-19 pandemic.

Abstract C061: Neighborhood racial context and race- and subtype-specific breast cancer incidence among non-Hispanic Black and non-Hispanic White women in California, 2006-2015

Abstract BACKGROUND: Determinants of racial inequities in risk of subtype-specific breast cancers are poorly understood. Features of the neighborhood context may contribute to racial inequities along the breast cancer continuum, however few have examined subtype-specific incidence. Therefore, this study aimed to characterize the association between the neighborhood racial context (housing discrimination and racial composition) and race- and subtype-specific breast cancer incidence among NH Black and NH White women in California. METHODS: We merged data from the California Cancer Registry on women aged 20+ diagnosed with primary breast cancer between 2006-2015 with neighborhood racial context at time of diagnosis: census tract % NH Black and a new racial bias index derived using 2007-2013 data from the Home Mortgage Disclosure Act. We used Poisson regression to estimate associations between neighborhood racial context and race- and Luminal A and TNBC (triple-negative breast cancer)-specific incidence rates, adjusting for neighborhood confounders. RESULTS: We identified n=104,716 cases of Luminal A and n=15,739 cases of TNBC over the study period. Among Black women, living in a high % Black census tract was associated with higher incidence of Luminal A (IRRadj=1.16 (1.08, 1.24)) and TNBC (IRRadj=1.17 (1.04, 1.32)) subtypes, relative to residence in low % Black tracts. No statistically significant association between neighborhood racial composition and either subtype was observed among NH Whites, nor between racial bias in mortgage lending and breast cancer among either racial group. CONCLUSION: Neighborhood racial composition may proxy cross-cutting social and environmental risk factors for breast cancer, regardless of subtype. These exposures may disproportionately burden Black versus White women with respect to breast cancer risk. Citation Format: Eli K. Michaels, Kirsten M.M. Beyer, Yuhong Zhou, Alison J. Canchola, Salma Shariff-Marco, Scarlett L. Gomez. Neighborhood racial context and race- and subtype-specific breast cancer incidence among non-Hispanic Black and non-Hispanic White women in California, 2006-2015 [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C061.

Abstract P6-11-13: Identification of barriers to breast cancer screening that affect compliance

Abstract Background: In 2015, the latest year for which the Center for Disease Control (CDC) has incidence data, 242,476 new cases of Female Breast Cancer were reported, and 41,523 women died of Female Breast Cancer in the United States. For every 100,000 women, 125 new Female Breast Cancer cases were reported and 20 died of cancer. In Arizona, breast was the leading site of new cancers in 2015, with 110.9 new breast cancer diagnoses per 100,000 women, and is second for cancer deaths, reporting 19 deaths per 100,000 women. This study specifically addresses low screening rates among women in Pima County in Southern Arizona through a telephone navigation program with the goal of increasing follow-up mammograms and recommended breast imaging. Our short-term goal is to increase both initial screening and diagnostic resolution rates among women in Southern Arizona. Our long-term plan is to develop a sustainable model to increase breast cancer screening among women that is expected to inform programs state-wide and nationally. Specific aims are: 1) to increase adherence or repeat screening rate by 20% for women lost to follow-up; 2) Establish the framework for a community-academic partnership that can be replicated in other Hispanic-based areas. Methods: Potential study participants were identified using Electronic Health Records and categorized by Breast Imaging-Reporting and Data System (BI-RADS) 0 to 5. Inclusion criteria include non-compliant women of any race/ethnicity between the ages of 40 and 75 who have been referred to, or seen at a breast imaging clinic in Tucson, Arizona (Pima County) from January 1, 2014 to September 30, 2017. Of those non-compliant, 47% had a BI-RADS 0,3,4, or 5. With IRB approval from University of Arizona, we adapted a questionnaire validated for use in colon cancer to measure screening knowledge, motivations and barriers to adherence, and self-efficacy. Two navigators reached out to participants to recruit and re-engage them in the care process. Results: The sample is n=9661 of noncompliant patients from a clinic in Southern Arizona, 26% were Hispanic and 65% non-Hispanic, with 10% with 9% requiring an interpreter. From this sample, 123 study participants have been recruited (300 target accrual) with a 21% recruitment rate, 46% unable to reach rate, and a 47% decline rate. Notably, of those who declined, 66% reported being compliant at another clinic. The participants were 46% non-Hispanic and 52% Hispanic, with 25% requiring an English/Spanish interpreter. Nearly half had less than or a high school degree and similarly, nearly half had a monthly family income of $2000 or less. On the questionnaire section of knowledge, there were no statistically significant results indicating extensive knowledge, except for how often one should have a mammogram, in which 93% answered correctly. On the Barriers to Getting a Mammogram section, when the data was disaggregated by ethnicity, there was statistically significant (P⇒.05) responses. One barrier identified was financial reasons (P=.05), but interestingly no (0) Hispanics reported financial reasons to be a barrier. Conclusion: The high number of declined due to compliant elsewhere points to the need to develop a business case to sustain lay navigators across the breast cancer continuum, from screening to diagnostic resolution, treatment, survivorship, and/or palliative care. Further, breast cancer and breast screening education materials will be developed in the next phase of this study and interventions to address financial reasons. For more information on this study, please contact Drs. Jorge Gomez (Jorgejgomez@email.arizona.edu), Allison Huff MacPherson (allison7@email.arizona.edu). Citation Format: Allison Huff MacPherson, Jorge Gomez, Elizabeth Calhoun, Marisa Borders, Kimberly Fitzpatrick, Yessenia Prado, Dora Bezies-Lopez, Chiu-Hsieh Hsu. Identification of barriers to breast cancer screening that affect compliance [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-13.

Healthcare system distrust and the breast cancer continuum of care.

To identify and synthesize the literature on healthcare system distrust across the breast cancer continuum of care. We searched CINAHL, Cochrane, EMBASE, PubMed, PsycINFO, and Web of Science from January 1, 1990 to December 31, 2018 for all peer-reviewed publications addressing the role of healthcare system trust, distrust or mistrust in the breast cancer continuum of care. We identified a total of 20 studies, seven qualitative studies and thirteen quantitative studies. Two studies assessed genetic testing, eleven assessed screening and seven assessed treatment and follow-up. Twelve studies evaluated mistrust, five evaluated distrust, and three evaluated trust. Study populations included African American, American Indian, Latina, Hispanic, and Asian American participants. Healthcare system distrust is prevalent across many different racial and ethnic groups and operates across the entire breast cancer continuum of care. It is an important yet understudied barrier to cancer. We hope that the knowledge garnered by this study will enable researchers to form effective and targeted interventions to reduce healthcare system distrust mediated disparities in breast cancer outcomes.

Exercise Training-induced Modulation in Microenvironment of Rat Mammary Neoplasms.

Despite the importance attributed to exercise training in the breast cancer (BC) continuum, the underlying mechanisms modulating tumor behavior are unknown. We evaluated the effects of long-term moderate-exercise in the development of mammary tumors, and studied the microenvironment of infiltrative lesions, the amount of connective tissue, and balance between cellular proliferation/death.Fifty Sprague-Dawley rats, randomly assigned into four groups: two control groups (sedentary and exercised) and two models of BC groups (sedentary and exercised) induced by N-methyl-N-nitrosoureia (MNU), were sacrificed after 35 weeks of moderate-exercise, and all perceptible tumors were removed for histological and immunohistochemistry analysis.The median number of infiltrative-lesions per animal was lower in the MNU exercised animals (p=0.02). More than one histological pattern was identified, and papillary carcinoma was the most frequent in both groups. Within infiltrative-lesions, the number of immunopositive cells per μm2 of Ki67 was lower in exercised animals (p=0.002). This presents increased cell death per μm2 (p=0.019). Tumors from sedentary animals had a higher expression of collagen deposition (p=0.027).Long-term moderate-exercise has beneficial effects in tumor development with a diminished prevalence of malignancy. Within infiltrative-lesions, moderate-exercise improves the balance between cell-proliferation and cell-death with decreased connective tissue that suggests lower tumor aggressiveness.

Abstract 606A: Biological predictors and the impact of cancer among African American women

Abstract African American women have a lower incidence of breast cancer yet, they have an overall higher mortality rate compared with women of other racial groups. Furthermore, some African American women are more likely to be diagnosed with breast cancer at an advanced stage when compared to other women and are also more likely to have biomarkers that are estrogen and progesterone receptor negative and have a greater propensity to be diagnosed with variant forms of breast cancer when compared with other women. These aforementioned factors may affect a women's quality of life. While the literature is robust with psychosocial and behavioral factors that contribute to the quality of life that African American women experience; to date, there has been a paucity of empirical data that have investigated the role of biological predictors and its effect on the lives of these women. To that end, the specific aim of this study was to test a model and investigate the role of biological risk factors estrogen receptors (ER), progesterone receptors (PR), triple negative breast cancer, Breast CAncer gene (BRCA1/2), Tumor Protein 53 gene (TP53, p53), age &amp;lt;45, Basal Metabolic Index (BMI), and age of first pregnancy that may affect the quality of life, thus having an impact on the lives of African American breast cancer survivors. These factors are hypothesized as impacting the quality of lives of these women and their families. The Impact of Cancer is defined as negative or positive occurrences/after-effects along the breast cancer continuum. The Impact of Cancer (IOCv2) captures the multidimensional aspect of the cancer experience that is specific for cancer survivors and their quality of life. Methods: As part of a larger cross-sectional study, breast cancer survivors completed a demographic data questionnaire inclusive of biological risk factors and the impact of cancer scale. A multiple linear regression was performed to determine the relationship between the two variables. Utilizing recruitment flyers, support groups and word-of-mouth, we recruited and screened 169 women from breast cancer support groups and community dwellers in Southern and Northern California. One hundred and sixty women were eligible and n=155 participated. Inclusion criteria were women who self-identified as African/Black American, age 25 year or older, diagnosis of breast cancer and at least 1-year post-active treatment. Results: Among the biological predictors, none were statistically significant as predictors of the impact of cancer in the lives of these survivors. The results revealed a trend in survivors who were diagnosed before age 45 (p=.077) that their breast cancer experience had a positive impact on their lives.Conclusion: Understanding biological predictors and the unique interplay of these roles may be necessary along the survivorship trajectory. Additional exploration of psycho social predictors and inclusion of specific moderators may be warranted. Citation Format: Claudia M. Davis. Biological predictors and the impact of cancer among African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 606A.

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.

Variations in outcomes by residential location for women with breast cancer: a systematic review

ObjectivesTo systematically assess the evidence for variations in outcomes at each step along the breast cancer continuum of care for Australian women by residential location.DesignSystematic review.MethodsSystematic searches of peer-reviewed articles...