Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00

Publikation

Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00

Wissenschaftlicher Artikel/Review - 02.07.2016

Pruneri Giancarlo, Regan Meredith M, Gelber Richard D, Munzone Elisabetta, Cancello Giuseppe, Price Karen N, Kammler Roswitha, Goldhirsch Aron, Gianni Lorenzo, Ruhstaller Thomas, Láng István, Criscitiello Carmen, Curigliano Giuseppe, Viale Giuseppe, Vingiani Andrea, Gray Kathryn P, Colleoni Marco

Zitation

Pruneri G, Regan M, Gelber R, Munzone E, Cancello G, Price K, Kammler R, Goldhirsch A, Gianni L, Ruhstaller T, Láng I, Criscitiello C, Curigliano G, Viale G, Vingiani A, Gray K, Colleoni M. Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00. Breast Cancer Res Treat 2016; 158:323-31.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Breast Cancer Res Treat 2016; 158

Veröffentlichungsdatum

02.07.2016

eISSN (Online)

1573-7217

Seiten

323-31

Kurzbeschreibung/Zielsetzung

The purpose of this study was to assess the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in the triple-negative breast cancer (TNBC) cohort of the phase III IBCSG trial 22-00, comparing low-dose oral 'metronomic' cyclophosphamide-methotrexate maintenance chemotherapy (CM-maintenance) to no-CM-maintenance in early breast cancer. TILs were evaluated in full-face hematoxylin-and-eosin-stained sections of tumor samples confirmed centrally as TNBC (< 1 % of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification). Mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor. The primary endpoint was breast cancer-free interval (BCFI). Cox proportional hazards regression model assessed the association of BCFI and secondary endpoints with TILs score. In the 647 tumor samples, the median percentage of TILs was 18 % (IQR = 8-40 %), with 18 % having TILs ≥ 50 % (lymphocyte-predominant breast cancer, LPBC). At a median follow-up of 6.9 years, TILs were associated with better prognosis. For every 10 % increase of TILs, BCFI risk reduction was 13 % (HR 0.87, 95 % CI 0.79-0.95,P = 0.003). DFS, DRFI, and OS risk reductions were 11 % (P = 0.005), 16 % (P = 0.003), and 17 % (P < 0.001), respectively. Multivariable analysis confirmed the independent prognostic value of TILs. No significant TILs-by-treatment interaction was observed (P = 0.39) for associations of TILs with BCFI, although patients with LPBC receiving CM-maintenance had a greater breast cancer risk reduction (HR 0.64,95 % CI 0.23-1.78) than those with non-LPBC (TILs < 50 %) (HR 0.96, 95 % CI 0.67-1.40). TILs score is a potent prognostic factor in patients with TNBC. Low-dose chemotherapy confers a greater (not statistically significant) clinical benefit in patients with LPBC.