Abstract CN02-02: From precision medicine to personalized medicine in metastatic breast cancer patients.
Authors: Andre Fabrice 
Published: August 2014

Abstract
Genomic characterisation of breast cancers has shown that this disease includes large number of genomic segments. Each genomic segment is characterized by a genomic alteration involved in cancer progression. As illustration, PIK3CA, FGFR1, AKT1, PTEN, FGFR1, EGFR, IGF1R, ESR1, ERBB2 present gene copy number alteration or mutations between 1 and 30% of the breast cancer samples. Interestingly, most of the studies that aim at characterizing breast cancer have used primary tumors, but not metastatic samples. Precision medicine is the development of targeted therapy in a disease segment characterized by the molecular alteration that defines sensitivity to the investigational drug. In the breast cancer field, several drugs are being developed in genomic segments. As illustration, FGFR inhibitors are being developed in patients who present FGFR1 or FGFR2 amplification. Early trials have suggested that these drugs could lead to antitumor effect in patients presenting this alterations. Other therapies are being tested in rare genomic segments, including AKT1 inhibitors. These therapeutic trials have shown that patient accrual is a major challenge and several actions are being taken to address this issue. First, several large cooperative groups are performing large scale molecular screening in order to increase the number of patients with a specific genomic alteration. As illustration, we recently performed the SAFIR01 trial that included 423 patients with metastatic breast cancer. A genomic alteration could be identified in 194 patients and 48 patients received a targeted therapy according to this genomic alteration. With regards to molecular screening, the use of circulating DNA to screen patients from satellite average volume centers is particularly attractive. Second, some clinical trials now merge "genomic segments" according to the functional pathways using either gene expression signatures or phosphoprotein assays. Finally, some could argue that drug development in rare genomic segments is not sustainable because of the difficulties to recruit patients. In this latter case, one solution to overcome this issue could be to test genomic algorithm for treatment sensitivity and no longer drugs themselves. As illustration, we are currently launching SAFIR02 trial that will evaluate the medical usefulness of a genomic algorithm that will screen sensitivity for 8 different targeted therapies. This trial is planned to include 200 patients with targetable genomic alterations. One of the major limitations of such approach based on oncogen de-addiction is the occurrence of resistance to targeted therapies. In order to delay or avoid such resistance, several approaches are being developed that include the selection of patients with low level of genomic instability/intratumor heterogeneity, combination with immunotherapeutics, and DNA repair modulators. In conclusion, drug development in genomic segment is facing the challenge of patient accrual and therefore needs the development of large scale molecular screening programs. First results of these programs show that genomic screening is feasible. Further development includes the evaluation of genomic algorithm and combination with immunotherapeutics
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):CN02-02.
Citation Format: Fabrice Andre. From precision medicine to personalized medicine in metastatic breast cancer patients. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr CN02-02.