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

L W de Boo, K Jóźwiak, N D Ter Hoeve, P J van Diest, M Opdam, Y Wang, M K Schmidt, V de Jong, S Kleiterp, S Cornelissen, D Baars, R H T Koornstra, E D Kerver, T van Dalen, A D Bins, A Beeker, S M van den Heiligenberg, P C de Jong, S D Bakker, R C RietbroekI R Konings, R Blankenburgh, R M Bijlsma, A L T Imholz, N Stathonikos, W Vreuls, J Sanders, E H Rosenberg, E A Koop, Z Varga, C H M van Deurzen, A L Mooyaart, A Córdoba, E Groen, J Bart, S M Willems, V Zolota, J Wesseling, A Sapino, E Chmielik, A Ryska, A Broeks, A C Voogd, E van der Wall, S Siesling, R Salgado, G M H E Dackus, M Hauptmann, M Kok, S C Linn*

*Corresponding author for this work

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Abstract

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
Volume9
Issue number3
Early online date6 Mar 2024
DOIs
Publication statusPublished - Mar 2024

Keywords

  • fibrotic focus
  • lymphovascular invasion
  • prognostic biomarkers
  • stromal tumor-infiltrating lymphocytes
  • triple-negative breast cancer

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