Tumor-Associated Neutrophils in Breast Cancer Subtypes

Background: Tumor associated neutrophils (TAN) are related to aggressiveness and a poor prognosis with human cancers. However, the relevance of TAN in breast cancer has not been previously investigated and here we sought to determine their presence among different subtypes. Methods: We analyzed patients with stage I-III breast cancers between 2006 and 2012. Tumors were divided into three subtypes: hormone-receptor [ HR]-positive, HER2-negative (HR+,HER2-ve); HER2-positive and triple negative (TN). Hematoxylin and eosin stained sections were examined and the number of TAN per 10 high power fields (HPF, 40x) was recorded. Tumors with >1 TAN per 10 HPF were considered TAN-positive. Fisher’s exact test was used to test for independence between qualitative variables, and logistic regression models were applied for multivariate analysis. Results: A total of 133 patients were assessed for inclusion and 105 were analyzed (28 excluded on various criteria). Some 72 tumors (69%) were classified as HR+, HER2-ve, 15 (14%) as HER2+ and 18 (17%) as TN. Totals of 16 TN (88%), 8 HER2+ (53%) and 4 HR+, HER2-ve tumors (5%) were TAN+ (p<0.001), including 79% of HR-ve tumors (19 of 24), in contrast to 11% of their HR+ve counterparts (9 of 81) (p<0.001). HER2 expression (p=0.023) and tumor grade (p<0.001) were also associated with TAN positivity. On multivariate analysis, only HR negativity (OR 16.85; 95% CI 4.4-64.6, p=<0.0001) was associated with a higher likelihood of TAN positivity. Conclusions: TAN are present in most TN tumors. We found an absence of HR expression to be the only predictor of TAN positivity. These results raise the question as to whether TAN, as part of the tumor microenvironment, have a role in the aggressiveness and progression of TN tumors and thus warrant further investigation in this breast cancer subtype, particularly in relation to response to treatment and prognosis.