We previously observed T-bet positive lymphocytes to be associated with a good prognosis in a cohort of women with familial breast cancer. To validate this finding, we evaluated lymphocyte T-bet expression in an independent unselected prospectively accrued series of women with lymph node negative breast carcinoma. T-bet and clinical-pathologic data were available for 614 women. Hormone receptors, HER2, Ki67, CK5, EGFR, p53 and T-bet status were determined using immunohistochemical (IHC) and/or biochemical methods. Tumors were assigned to luminal A, luminal B, HER2 and basal subtypes based on the expression of IHC markers. Multiple cutpoints were examined in a univariate penalized Cox model to stratify tumors into T-bet+/high and T-bet-/low. Fisher's exact test was used to analyze T-bet associations with clinical-pathologic variables, IHC markers and molecular subtype. Survival analyses were by the Cox proportional hazards model. All tests were two-sided. A test with a P-value < 0.05 was considered statistically significant. T-bet+/high tumor status was significantly associated with large tumor size, high grade, hormone receptor negativity, CK5, EGFR and p53 positivity, high Ki67 and basal subtype. With a median follow-up of 96.5 months, T-bet-/low tumor status was associated with a reduced disease free survival compared with T-bet+/high tumor status in multivariate analysis (P=0.0027, RR=5.62, 95% CI: 1.48-50.19). Despite being associated with adverse clinical-pathologic characteristics, T-bet+ tumor infiltrating lymphoid cells are associated with a favorable outcome. This supports its role in Th1-mediated anti-tumor activity and may provide insight for the development of new therapeutic strategies.
- Received February 20, 2015.
- Revision received August 7, 2015.
- Accepted August 24, 2015.
- Copyright © 2015, American Association for Cancer Research.