Prognostic and predictive value of tumor-infiltrating lymphocytes in node-positive breast cancer

We and others have previously shown that an immune signal can influence prognosis and response to treatment, particularly “immunogenic therapies” in specific breast cancer subtypes, such as those estrogen receptor (ER)-negative and/or overexpressing the HER2/neu oncogene. To validate this further and determine immunity could be a clinically relevant biomarker, we evaluated the association between quantity of tumor infiltrating lymphocytes (TILs) in a breast cancer, prognosis and prediction of response to anthracyline chemotherapy in a large clinical trial in over 2000 primary breast cancers and long term follow-up data. We found that TILs were strongly associated with a good prognosis in the triple negative breast cancer (TNBC: ER, PGR, and HER2-negative) subtype- even node positive TNBCs had an excellent survival if they were observed to have high amounts of TILs at diagnosis. Their outcome did not seem to depend on the type of chemotherapy that they were given. In contrast, those HER2+ BCs and high TILs had a much better survival if they received a higher dose of anthracycline instead of combination anthracycline-taxane. Given the data regarding immunogenic cell death and its contribution to treatment efficacy, this suggests that some for HER2+ BCs, tumor mediated immune evasion and suppression could strongly influence clinical outcomes- hence a treatment that can be immune modulating could be of benefit. This data deserve additional validation as a clinical prognostic marker for TNBC (stratification for clinical trials etc) and further research into the immune effects of anti-HER2 therapies and how these could be modified by therapeutic agents  

Bibliographic Reference:

Loi S et al.: "Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in a Phase III Randomized Adjuvant Breast Cancer Trial in Node-Positive Breast Cancer Comparing the Addition of Docetaxel to Doxorubicin With Doxorubicin-Based Chemotherapy: BIG 02-98", J Clin Oncol. 2013 Jan 22. [Epub ahead of print]

Sherene Loi

Translational Breast Cancer Genomics Lab, Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia