Sherene Loi1, Nicolas Sirtaine1, Fanny Piette1, Roberto Salgado1, Giuseppe Viale1, Françoise Van Eenoo1, Ghizlane Rouas1, Prudence A. Francis1, John Crown1, Erika Hitre1, Evandro de Azambuja1, Emmanuel Quinaux1, Angelo Di Leo1, Stefan Michiels1, Martine Piccart1, Christos Sotiriou1
1Sherene Loi, Nicolas Sirtaine, Roberto Salgado, Françoise Van Eenoo, Ghizlane Rouas, Stefan Michiels, Martine J. Piccart, and Christos Sotiriou, Institut Jules Bordet, Brussels; Fanny Piette and Emmanuel Quinaux, International Drug Development Institute, Louvain-la-Neuve, Belgium; Giuseppe Viale, University of Milan, Milan; Angelo Di Leo, Hospital of Prato, Prato, Italy; Prudence Francis, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australian and New Zealand Breast Cancer Trials Group, Newcastle,...
Tóm tắt
Purpose Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT—in this case, anthracycline-only CT—in selected BC subtypes. Patients and Methods We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. Results There was no significant prognostic association in the global nor estrogen receptor (ER) –positive/human epidermal growth factor receptor 2 (HER2) –negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). Conclusion In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.
