Title: CD3 and CD20 lymphocytes infiltration to predict chemosensitivity in patients with triple negative breast cancer.

Project Coordinator:
Fabrice ANDRE (France) Gustave Roussy Institute, INSERM Unit U981, Villejuif

Project Partners:
Hervé BONNEFOI (France) UNICANCER, Breast Medical Oncology, Bordeaux
Giuseppe CURIGLIANO (Italy) Istituto Europeo di Oncologia, Breast Medical Oncology, Milano
Carsten DENKERT (Germany) Charité Hospital, Pathology, Berlin
Sibylle LOIBL (Germany) German Breast Group, Gynecology, Neu-Isenburg

Project Abstract:
Triple negative breast cancer accounts for around 15-20% of overall breast cancers. These cancers are characterized by aggressive features and lack of validated targeted therapies. Although a subset of these patients presents high sensitivity to chemotherapy, most of the patients do not achieve pathological complete response, (pCR) neoadjuvant chemotherapy. Since this molecular segment is associated with high rate of relapse, it is the focus of large efforts in drug development. Recent data have suggested that lymphocyte infiltration, mainly CD3 and CD20, could be associated with a high sensitivity to chemotherapy. Additional data have further suggested that such infiltration could be associated with good prognosis in this patient’s population. The validation of CD3-CD20 as predictor for high sensitivity to chemotherapy could lead to limit drug development in patients who present with CD3/CD20-negative infiltration or large tumor bulk. The primary aim of the present study will be to validate the predictive and prognostic value of CD3/CD20 infiltration for the efficacy of neoadjuvant chemotherapy in triple negative breast cancer. In order to achieve this goal, we will perform a prospective trial that will include 200 patients. This trial will prospectively evaluate the predictive value of CD3/CD20 infiltration in the neoadjuvant setting. Pathological complete response will be taken as surrogate, endpoint for long term survival, because it could be shown that pCR predicts excellent disease free and averall survival in TNBC. In addition, the prognostic value of CD3/CD20 will be evaluated in 1000 patients with TNBC previously included in randomized clinical trials. Secondary endpoints will include the evaluation of T cell Repertoire (TcR) repertoire after chemotherapy, the investigation of Rad51 / HMGB1 induction by chemotherapy.

Publishable Summary:
This research consortium has generated two advances. First, it has shown that postchemotherapy lymphocytic infiltration is associated with very good outcome. This has further been validated in two others independent cohorts. The consortium then developed a gene expression signature based on baseline samples to predict which patients will present a lymphocytic infiltration after chemotherapy. A 4-gene signature was developed and patented. The prognostic value of this signature has been shown in discovery set and independent cohorts.


(Project funded under JTC 2011)