Purpose: The prognostic role of tumor-infiltrating lymphocytes (TILs) in ER+/HER2− breast cancer (BC) is debated. We evaluated the association of TILs and clinico-pathological features with distant disease-free survival (DDFS) in patients with ER+/HER2− BC treated at a single institution. Patients and methods: A mono-institutional case-cohort series of 987 patients with early ER+/HER2− BC was retrospectively analyzed. TILs were considered both as continuous variable, and dichotomized in low (< 5%) vs high (≥ 5%). The main outcome was DDFS. Median follow-up was 7.5 years (0.1–10). Univariate and multivariable Cox proportional hazards regression with inverse sub-cohort sampling probability weighting were used to evaluate the risk across groups. Results: Median TIL count was 2% (Q1–Q3 1–4%). Higher TILs were positively associated with number of lymph nodes involved (p = 0.003), tumor grade (p < 0.0001), peritumoral vascular invasion (p = 0.003), higher Ki-67 (p = 0.0001), luminal B subtype (p < 0.0001), and chemotherapy use (p < 0.00019). In multivariable regression analysis, only higher Ki-67 expression retained significant association with TILs. At univariate Cox regression analysis, TIL expression (≥ 5% vs. < 5%) was not associated with DDFS (HR 1.08, 95% CI 0.80–1.46, p = 0.62). In patients treated with adjuvant chemotherapy, high TILs were associated with better DDFS (HR 0.52, 95%CI 0.33–0.83, p = 0.006), particularly in the group with Ki-67 ≥ 20% (HR 0.50, 95%CI 0.29–0.86, p = 0.01). Conclusion: High TILs in ER+/HER2− BC are significantly associated with clinico-pathological features of dismal outcome. TIL prognostic value seems different in patients treated with or without chemotherapy. Our findings suggest that the high-risk subgroup might be more immunogenic, thus deserving the exploration of immunotherapy approaches.

Tumor-infiltrating lymphocytes (TILs) in ER+/HER2− breast cancer / C. Criscitiello, A. Vingiani, P. Maisonneuve, G. Viale, G. Viale, G. Curigliano. - In: BREAST CANCER RESEARCH AND TREATMENT. - ISSN 0167-6806. - 183:2(2020 Sep 01), pp. 347-354. [10.1007/s10549-020-05771-7]

Tumor-infiltrating lymphocytes (TILs) in ER+/HER2− breast cancer

C. Criscitiello;A. Vingiani
Secondo
;
G. Viale;G. Viale
Penultimo
;
G. Curigliano
Ultimo
2020

Abstract

Purpose: The prognostic role of tumor-infiltrating lymphocytes (TILs) in ER+/HER2− breast cancer (BC) is debated. We evaluated the association of TILs and clinico-pathological features with distant disease-free survival (DDFS) in patients with ER+/HER2− BC treated at a single institution. Patients and methods: A mono-institutional case-cohort series of 987 patients with early ER+/HER2− BC was retrospectively analyzed. TILs were considered both as continuous variable, and dichotomized in low (< 5%) vs high (≥ 5%). The main outcome was DDFS. Median follow-up was 7.5 years (0.1–10). Univariate and multivariable Cox proportional hazards regression with inverse sub-cohort sampling probability weighting were used to evaluate the risk across groups. Results: Median TIL count was 2% (Q1–Q3 1–4%). Higher TILs were positively associated with number of lymph nodes involved (p = 0.003), tumor grade (p < 0.0001), peritumoral vascular invasion (p = 0.003), higher Ki-67 (p = 0.0001), luminal B subtype (p < 0.0001), and chemotherapy use (p < 0.00019). In multivariable regression analysis, only higher Ki-67 expression retained significant association with TILs. At univariate Cox regression analysis, TIL expression (≥ 5% vs. < 5%) was not associated with DDFS (HR 1.08, 95% CI 0.80–1.46, p = 0.62). In patients treated with adjuvant chemotherapy, high TILs were associated with better DDFS (HR 0.52, 95%CI 0.33–0.83, p = 0.006), particularly in the group with Ki-67 ≥ 20% (HR 0.50, 95%CI 0.29–0.86, p = 0.01). Conclusion: High TILs in ER+/HER2− BC are significantly associated with clinico-pathological features of dismal outcome. TIL prognostic value seems different in patients treated with or without chemotherapy. Our findings suggest that the high-risk subgroup might be more immunogenic, thus deserving the exploration of immunotherapy approaches.
Adjuvant therapy; Chemotherapy; Early breast cancer; Luminal subtype; Tumor-infiltrating lymphocytes
Settore MED/06 - Oncologia Medica
Settore MED/08 - Anatomia Patologica
1-set-2020
lug-2020
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/758344
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