Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Leonora W. de Boo, Katarzyna Jóźwiak, N.D. ter Hoeve, Paul J. van Diest, Mark Opdam, Y. Wang, Marjanka K. Schmidt, V. de Jong, S. Kleiterp, Sten Cornelissen, D. Baars, R.H.T. Koornstra, E. D. Kerver, Thijs van Dalen, A.D. Bins, A. Beeker, Simone M. van den Heiligenberg, P.C. de Jong, S.D. Bakker, R.C. RietbroekI.R. Konings, R. Blankenburgh, R.M. Bijlsma, Alex Imholz, Nikolas Stathonikos, Willem Vreuls, Joyce Sanders, Efraim H. Rosenberg, Esther Koop, Z. Varga, Carolien H.M. van Deurzen, A. Mooyaart, Alicia Cordoba, Emilie J. Groen, Joost Bart, Stefan M. Willems, Vicky Zolota, Jelle Wesseling, Anna Sapino, Ewa Chmielik, Ales Ryska, Annegien Broeks, Adri C. Voogd, E. van der Wall, Sabine Siesling, R. Salgado, Gwen M.H.E. Dackus, Michael Hauptmann, Marleen Kok, Sabine C. Linn

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Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Original languageEnglish
Article number102923
JournalESMO Open
Issue number3
Publication statusPublished - 6 Mar 2024


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