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

Tulay Koru-Sengul, Ana M. Santander, Feng Miao, Lidia G. Sanchez, Merce Jorda, Stefan Glück, Tan A. Ince, Mehrad Nadji, Zhibin Chen, Manuel L. Penichet, Margot P. Cleary, Marta Torroella-Kouri

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)113-126
Number of pages14
JournalBreast Cancer Research and Treatment
Volume158
Issue number1
DOIs
StatePublished - Jul 1 2016

Bibliographical note

Funding Information:
We would like to extend our thanks to the University of Miami Sylvester Comprehensive Cancer Center’s Tissue Bank Core Facility and the Tumor Registry, and particularly to Drs. Consuelo Alvarez and Clara Milikowski without whom this investigation would not have been carried out. This study was funded by the Braman Family Breast Cancer Institute Development Grant from Sylvester Comprehensive Cancer Center at University of Miami Miller School of Medicine and also in part by the NCI/NIH R21CA176055 both to MTK. Research for this article was supported in part by funding to T.A.I from Breast Cancer Research Foundation and Play for P.I.N.K., NIEHS R01-ES024991, Women’s Cancer Association of UM and Sylvester Comprehensive Cancer Center; to L.G.S from a supplement to R21CA176055, to ZC from R21CA178675; to MLP from R01CA181115 and to M.P.C. from R01CA157012.

Publisher Copyright:
© 2016, Springer Science+Business Media New York.

Keywords

  • Breast cancer
  • Crown-like structures
  • Inflammation
  • Macrophages
  • Race/ethnicities

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