Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy |
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| Affiliation: | 1. Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul;2. Department of Hemato-Oncology, Konkuk Medical Center, University of Konkuk College of Medicine, Seoul, Korea;3. Department of Biostatistics and Epidemiology, Gustave Roussy;4. INSERM, Unit 1018, University Paris-Sud, University Paris-Saclay, Villejuif;5. Department of Pathology, Institut Curie, Université Paris Sciences Lettres, Paris, France;6. IEO, European Institute of Oncology, IRCCS, Milan, Italy;7. GZA, Antwerp, Belgium;8. Division of Clinical Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;9. Department of Pathology, European Institute of Oncology, IRCCS, Milano, Italy;10. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;11. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova;12. Veneto Institute of Oncology IOV – IRCCS, Padova, Italy;13. Inserm Unit 934, Paris, France;14. Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy;15. Department of Oncology, Gustave Roussy;16. INSERM, Unit 981, University Paris-Sud, University Paris-Saclay, Villejuif, France |
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| Abstract: | BackgroundAlthough stromal tumor-infiltrating lymphocytes (sTILs) have been considered an important prognostic factor in early-stage triple-negative breast cancer (TNBC), there have been limited data on their prognostic value in the absence of adjuvant chemotherapy.Patients and methodsA pooled analysis was carried out using four cohorts of TNBC patients not treated with chemotherapy. sTILs were evaluated in the most representative tumoral block of surgical specimens. Cox proportional hazards regression models were used for invasive disease-free survival (iDFS), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors.ResultsWe analyzed individual data of 476 patients from 4 centers diagnosed between 1989 and 2015. Their median age was 64 years. The median tumor size was 1.6 cm and 83% were node-negative. The median level of sTILs was 10% (Q1−Q3, 4%−30%). Higher grade was associated with higher sTILs (P < 10−3). During follow-up, 107 deaths, and 173 and 118 events for iDFS and D-DFS were observed, respectively. In the multivariable analysis, sTILs obtained an independent prognostic value for all end points (likelihood ratio χ2 = 7.14 for iDFS; P < 10−2; χ2 = 9.63 for D-DFS, P < 10−2; χ2 = 5.96 for OS, P = 0.015). Each 10% increment in sTILs corresponded to a hazard ratio of 0.90 [95% confidence interval (CI) 0.82 − 0.97] for iDFS, 0.86 (95% CI 0.77 − 0.95) for D-DFS, and 0.88 (95% CI 0.79 − 0.98) for OS, respectively. In patients with pathological stage I tumors with sTILs ≥30% (n = 74), 5-year iDFS was 91% (95% CI 84% to 96%), D-DFS was 97% (95% CI 93% to 100%), and OS was 98% (95% CI 95% to 100%).ConclusionsTILs add important prognostic information in systemically untreated early-stage TNBC patients. Notably, sTILs can identify a subset of stage I TNBC patients with an excellent prognosis without adjuvant chemotherapy. |
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