Abstract 1286: Macrophages in the breast tumor microenvironment as a prognostic factor among race/ethnicity
Authors: Santander Ana M. , Koru-Sengul Tulay , Miao Feng , Jorda Merce , Gluck Stephan , Alvarez Consuelo , Milikowski Clara , Perez Osvaldo , Nadji Mehrdad , Carrio Roberto , Lopez-Ocejo Omar , Torroella-Kouri Marta 
Published: August 2015

Breast cancer is the second leading cause of death by cancer in women in the United States. The occurrence of high numbers of macrophages in the tumor stroma has been associated with tumor progression and poor prognosis in breast and other solid malignances; however macrophage numbers have not been validated as a standard prognostic factor in the clinical practice. Breast adipose tissue is also part of the breast tumor microenvironment, and macrophages are observed in fat tissue surrounding dead adipocytes in “crown-like structures” (CLS). CLS have also been associated with poor survival in breast cancer; however they are not currently used in the assessment of breast cancer prognosis in the clinical practice either. This study was designed to determine whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ macrophages in the breast adipose tissue (CLS) are independent prognostic factors in breast cancers across three different ethnic groups, African American, Latinas and Caucasian women. We also analyzed the polarization of macrophages as pro-inflammatory M1 (CD40+) and immunosuppressive M2 (CD206+) types, across these three ethnicities. A retrospective analysis of 150 breast cancer cases encompassing these three ethnic groups was carried out. African American and Latina women present with less incidence but more aggressive breast cancer disease and therefore, proportionally higher death rates. Using immunohistochemistry (IHC), we sought to identify whether there were any associations between the numbers of CD163+ TAMs and CLS with overall survival in these groups. Our findings show a statistically significant relationship between ethnicity and CD163+ macrophages located in the breast cancer microenvironment (TAMs/CLS) and reveal that the highest numbers of CD163+ TAMs/CLS are found in African American breast cancer patients. Latinas precede Caucasian breast cancer patients when assessing the numbers of CD163+ TAMs/CLS that were found, and Caucasian breast cancer patients show the lowest number of CD163+ TAMs/CLS. Using univariate survival analysis, our results show that the numbers of CD163+ TAMs and their M2 activation profile (CD206+) are associated with lower patient survival, whereas M1 (CD40+) macrophages are associated with higher patient survival. Univariate survival analysis also shows that the number of CLS exhibiting both M2/ M1 macrophages is associated with lower patient survival. We reveal for the first time that race/ethnicity is significantly associated with the number of TAMs and CLS in breast cancer.

Citation Format: Ana M. Santander, Tulay Koru-Sengul, Feng Miao, Merce Jorda, Stephan Gluck, Consuelo Alvarez, Clara Milikowski, Osvaldo Perez, Mehrdad Nadji, Roberto Carrio, Omar Lopez-Ocejo, Marta Torroella-Kouri. Macrophages in the breast tumor microenvironment as a prognostic factor among race/ethnicity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1286. doi:10.1158/1538-7445.AM2015-1286