Macrophages as independent prognostic factors in small T1 breast cancers

Abstract

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 malignancies. However, macrophage numbers in tumors have not been validated as a prognostic factor in clinical practice. The present analysis was designed as a pilot study aimed at determining whether the presence of CD68+ macrophages is an independent prognostic factor in small T1 estrogen receptor (ER)+ breast cancers across three different ethnic groups, i.e. African-American, Latina and Caucasian women. A retrospective pilot analysis of 30 T1 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 immuno-histochemistry, we sought to identify whether there was any association between the presence and density of CD68+ macrophages and standard prognostic markers with overall survival in these groups. Our data revealed that overall survival did not differ significantly for the occurrence or density of CD68+ macrophages in T1 ER+ tumors. There were also no significant differences in overall survival for the occurrence of CD68+ macrophages across ethnicities, although macrophage numbers were significantly higher in tumors from African-American and Latina than in Caucasian patients. Importantly, but not surprisingly, the absence of the progesterone receptor was associated very strongly with decreased overall survival. This pilot project shows that CD68+ macrophages are not pivotal in determining tumor prognosis in early T1 breast cancers. New studies are presently being conducted to assess the value of different macrophage markers and macrophage activation profiles as prognostic factors in breast cancers of different clinical stages, using a larger number of patients among these three different ethnicities.