Validation of Intratumoral T-bet+ Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer
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Validation of T-bet positive lymphoid cells as a prognostic biomarker in breast cancer; 'validation' here is clinical biomarker confirmation, the polysemy trap, and the object is prognosis.
The term validation refers to confirming a cancer biomarker's prognostic association, not studying research validation practices.
Clinical biomarker validation of T-bet+ cells for breast-cancer prognosis; polysemy of validation, domain oncology.
Abstract
We previously observed T-bet(+) 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 clinicopathologic data were available for 614 women. Hormone receptors, HER2, Ki-67, CK5, EGFR, p53, and T-bet status were determined using 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 exact test was used to analyze T-bet associations with clinicopathologic 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 Ki-67, 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; relative risk = 5.62; 95% confidence intervals, 1.48-50.19). Despite being associated with adverse clinicopathologic characteristics, T-bet(+) tumor-infiltrating lymphoid cells are associated with a favorable outcome. This supports their role in Th1-mediated antitumor activity and may provide insight for the development of new therapeutic strategies.
Stored with the screening record, where it is evidence for the labels above.
The record
- Venue
- Cancer Immunology Research
- Topic
- Cancer Immunotherapy and Biomarkers
- Field
- Medicine
- Canadian institutions
- Mount Sinai HospitalLunenfeld-Tanenbaum Research InstitutePublic Health OntarioUniversity of TorontoUniversity Health Network
- Funders
- Canadian Institutes of Health Research
- Keywords
- Breast cancerMedicineOncologyInternal medicineProportional hazards modelUnivariate analysisSurvival analysisPathologyCancerMultivariate analysisGastroenterology
- Has abstract in OpenAlex
- yes