Messaggi chiave
- Al fine di studiare l’associazione tra livelli di linfociti infiltranti il tumore (TIL) nel tessuto tumorale e sopravvivenza in pazienti con carcinoma mammario triplo negativo (TNBC) in stadio precoce non sottoposte a chemioterapia, è stata condotta un’analisi retrospettiva aggregata dei dati individuali di 1966 pazienti con diagnosi di TNBC ricevuta tra il 1979 e il 2017.
- I tassi a 5 anni di sopravvivenza libera da recidiva a distanza (RFDS) e sopravvivenza globale (OS) sono stati pari al 94 vs 78% e 95 vs 82% per le pazienti in stadio I con livelli di TIL ≥50% rispetto a <30%. A un follow-up mediano di 18 anni, dopo aggiustamento per altre variabili clinico-patologiche, ogni incremento >10% dei livelli di TIL è risultato associato in modo indipendente a un miglioramento degli esiti di sopravvivenza libera da malattia invasiva, RFS, DRFS e OS.
- I risultati della presente analisi suggeriscono un ruolo prognostico dei livelli di TIL nel tessuto tumorale in pazienti con TNBC in stadio precoce sottoposte a terapia locoregionale, ma non avviate a trattamento chemioterapico adiuvante o neoadiuvante.
Abstract
Importance
- The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear.
Objective
- To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy.
Design, setting, and participants
- Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy.
Exposure
- TIL abundance in breast tissue from resected primary tumors.
Main outcomes and measures
- The primary outcome was invasive disease-free survival [iDFS].
- Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival.
- Associations were assessed using a multivariable Cox model stratified by participating center.
Results
- This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]).
- Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%.
- At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, p <10e-6).
Conclusions and relevance
- In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival.
- These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.