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Ann Oncol. 2015 Aug;26(8):1698-704. doi: 10.1093/annonc/mdv239. Epub 2015 May 20.

Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials.

Author information

1
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
2
Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France.
3
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
4
INSERM, Unit U981, Gustave Roussy, Villejuif Department of Medical Oncology, Gustave Roussy, Villejuif.
5
INSERM, Unit U981, Gustave Roussy, Villejuif Department of Medical Oncology, Gustave Roussy, Villejuif Université Paris Sud, Villejuif, France.
6
INSERM, Unit U981, Gustave Roussy, Villejuif aicha.goubar@gustaveroussy.fr.

Abstract

BACKGROUND:

Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines.

PATIENTS AND METHODS:

A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs.

RESULTS:

TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20-1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-).

CONCLUSIONS:

We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.

KEYWORDS:

adjuvant chemotherapy; anthracyclines; breast cancer; tumor-infiltrating lymphocytes

PMID:
25995301
PMCID:
PMC4511223
DOI:
10.1093/annonc/mdv239
[Indexed for MEDLINE]
Free PMC Article

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