Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells

AbstractCancer stem cells (CSCs) are defined by their unlimited self-renewal ability and their capacity to initiate and maintain malignancy, traits that are not found in most cells that comprise the tumor. Although current cancer treatments successfully reduce tumor burden, the tumor will likely recur unless CSCs are effectively eradicated. This challenge is made greater by the protective impact of the tumor microenvironment (TME), consisting of infiltrating immune cells, endothelial cells, extracellular matrix, and signaling molecules. The TME acts as a therapeutic barrier through immunosuppressive, and thereby tumor-promoting, actions. These factors, outside of the cancer cell lineage, work in concert to shelter CSCs from both the body's intrinsic anticancer immunity and pharmaceutical interventions to maintain cancer growth. Emerging therapies aimed at the TME offer a promising new tool in breaking through this shield to target the CSCs, yet definitive treatments remain unrealized. In this review, we summarize the mechanisms by which CSCs are protected by the TME and current efforts to overcome these barriers.</jats:p

Abstract P5-14-05: Are neighborhood and community factors associated with refusing breast cancer surgery?

Abstract Background: The importance of an individual’s community impacts cancer disparities and is intimately related to social determinants of health. Surgery refusal is associated with a high disease-specific mortality. Studies of factors associated with refusal of treatment for potentially curable breast cancer show personal factors including age, marital status, and insurance are at play. However, few studies have investigated whether community or area-based characteristics may affect receipt of surgery. Methods: We selected all women diagnosed with non-metastatic (Stage I-III) breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database. We focused on those who refused surgery comparing racial and ethnic differences between Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic all races. Yost index calculated as neighborhood socio-economic status (nSES- divided into tertiles) and RUCA code-derived rural-urban status were based on an NCI census tract-level index, a composite score that includes income, education, housing, and employment; the remaining community factor measures were based on county-level index. Sociodemographic and community differences were analyzed using Pearson’s Chi-Square tests and analysis of variance. Multivariate logistic regression of predictors of refusal of surgery and Cox-proportional hazard model of disease-specific mortality were performed. A p-value of 0.05 was considered statistically significant. Results: 2,155 (0.7%) of 322,538 people refused surgery (NHW: 1,435 (66.6%), NHB: 353(16.3%), Hispanic all races: 166(7.7%)). Surgery refusers were more likely to live in areas with high poverty (&amp;lt;200% level), lower education attainment, lower unemployment, higher percentage urban population, higher percentage foreign-born, higher rates of language isolation, and lower rates of women over 40 having undergone mammography in the previous two years. Multivariate analysis shows surgery refusal is associated with high percentage of having a bachelor’s degree or higher (OR: 1.29, 95% CI:1.05-1.60, p-value &amp;lt;0.05), high percentage of poverty (&amp;lt;200% of poverty) (OR: 1.50, 95% CI:1.04-2.16, p-value &amp;lt;0.05), and high percentage of urban population (OR: 1.26, 95% CI:1.06-1.49, p-value &amp;lt;0.01). Surgery refusal rates declined with increasing nSES. Breast cancer-specific mortality increased significantly for those who refused surgery (HR:3.92, 95% CI: 3.41-4.51, p-value &amp;lt;0.01). Conclusion: Risk of refusing surgery for an otherwise curable breast cancer is associated with residence in communities with the lowest nSES. These are communities disproportionately populated by racial and ethnic minorities. Given the high mortality associated with refusing surgery, further investigation into the reasons why women decline treatment is necessary. For women living in impoverished communities, culturally sensitive education on benefits of care may be appropriate, while women of means may face different challenges such as utilization of alternative medicine. Citation Format: Theresa Relation, Oindrila Bhattacharyya, Jay Fisher, Yaming Li, Allan Tsung, Ahmad Hamad, Amara Ndumele, Bridget Oppong. Are neighborhood and community factors associated with refusing breast cancer surgery? [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 P5-14-05.</jats:p

Racial Differences in Response to Neoadjuvant Chemotherapy: Impact on Breast and Axillary Surgical Management

Background: Neoadjuvant chemotherapy (NAC), an increasingly used method for breast cancer patients, has the potential to downstage patient tumors and thereby have an impact on surgical options for treatment of the breast and axilla. Previous studies have identified racial disparities in tumor heterogeneity, nodal recurrence, and NAC completion. This report compares the effects of NAC response among non-Hispanic white women and black women in relation to surgical treatment of the breast and axilla. Methods: A retrospective review of 85,303 women with stages 1 to 3 breast cancer in the National Cancer Database who received NAC between 1 January 2010 and 31 December 2016 was conducted. Differences in sociodemographic and clinical variables between black patients and white patients with breast cancer were tested. Results: The study identified 68,880 non-Hispanic white and 16,423 non-Hispanic black women who received NAC. The average age at diagnosis was 54.8 years for the white women versus 52.5 years for the black women. A higher proportion of black women had stage 3 disease, more poorly differentiated tumors, and triple-negative subtype. The black women had lower rates of complete pathologic response, more breast-conservation surgery, and higher rates of axillary lymph node dissection, but fewer sentinel lymph node biopsies. Axillary management for the women who were downstaged showed more use of axillary lymph node dissection for black women compared with sentinel lymph node biopsy. Conclusions: The black patients were younger at diagnosis, had more advanced disease, and were more likely to have breast-conservation surgery. De-escalating axillary surgery is being adopted increasingly but used disproportionately for white women