Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians.
Racial disparities in breast cancer incidence and outcome are a major health care challenge. Patients in the black race group more likely present with an early onset and more aggressive disease. The occurrence of high numbers of macrophages is associated with tumor progression and poor prognosis in solid malignancies. Macrophages are observed in adipose tissues surrounding dead adipocytes in "crown-like structures" (CLS). Here we investigated whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ CLS are associated with patient survival and whether there are significant differences across blacks, non-black Latinas, and Caucasians. Our findings confirm that race is statistically significantly associated with the numbers of TAMs and CLS in breast cancer, and demonstrate that the highest numbers of CD163+ TAM/CLS are found in black breast cancer patients. Our results reveal that the density of CD206 (M2) macrophages is a significant predictor of progression-free survival univariately and is also significant after adjusting for race and for HER2, respectively. We examined whether the high numbers of TAMs detected in tumors from black women were associated with macrophage proliferation, using the Ki-67 nuclear proliferation marker. Our results reveal that TAMs actively divide when in contact with tumor cells. There is a higher ratio of proliferating macrophages in tumors from black patients. These findings suggest that interventions based on targeting TAMs may not only benefit breast cancer patients in general but also serve as an approach to remedy racial disparity resulting in better prognosis patients from minority racial groups.
Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Tulay
T
Koru-Sengul
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Avenue Rosenstiel Medical School Building Suite 3123A, P.O. Box 016960 (R-138), Miami, FL, 33101, USA.
Ana M
AM
Santander
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Feng
F
Miao
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Avenue Rosenstiel Medical School Building Suite 3123A, P.O. Box 016960 (R-138), Miami, FL, 33101, USA.
Lidia G
LG
Sanchez
Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Merce
M
Jorda
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.|Celgene Corporation, Summit, NJ, USA.
Stefan
S
Glück
Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Tan A
TA
Ince
Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Mehrad
M
Nadji
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Avenue Rosenstiel Medical School Building Suite 3123A, P.O. Box 016960 (R-138), Miami, FL, 33101, USA.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Zhibin
Z
Chen
Division of Surgical Oncology, Department of Surgery, UCLA, Los Angeles, CA, USA.|Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.|UCLA AIDS Institute, UCLA, Los Angeles, CA, USA.|The Molecular Biology Institute, UCLA, Los Angeles, CA, USA.
Manuel L
ML
Penichet
Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
Margot P
MP
Cleary
Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA. mtorroella@med.miami.edu.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Avenue Rosenstiel Medical School Building Suite 3123A, P.O. Box 016960 (R-138), Miami, FL, 33101, USA. mtorroella@med.miami.edu.|Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. mtorroella@med.miami.edu.
Marta
http://orcid.org/0000-0003-3943-6656
M
Torroella-Kouri
D001741:Black or African American; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001943:Breast Neoplasms / Q000208:ethnology* / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D016019:Survival Analysis; D044465:White People; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface
Breast cancer; Crown-like structures; Inflammation; Macrophages; Race/ethnicities