Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients
Mechanisms of resistance have been studied for many years in various experimental models.
However, many drugs that are highly effective in experimental models at overcoming
resistance have been either ineffective or marginally active in preliminary clinical
studies. Thus after decades of study, most reviews of anti-cancer drug resistance still
focus largely on experimental models, which may not reflect resistance in humans. However,
recent studies have demonstrated that clinical resistance occurs in primary and metastatic
tumors that may have undergone significant molecular evolution due to treatment effects and
the selection of clones as recently shown in breast cancer.
Triple negative breast cancer is a subtype that carries a poor prognosis and a high
incidence of early metastatic recurrence. Furthermore, no target therapy is efficacious up
to now in this subtype. Thus, identification of mechanisms of resistance to available
therapies and prediction of tumoral response to various treatments could help in the
management of patients affected by this particularly aggressive type of breast cancer.
The goals of this study are two-fold. First, to build a biobank of blood and tissue
specimens, prior to starting chemotherapy and at a determined time-point (surgery or
progression of disease), from patients undergoing the chemotherapeutic treatments in the
neoadjuvant and metastatic settings. Second, to use cutting-edge molecular techniques
available in several Quebec research centers, to carefully compare these pre and post
treatment samples to identify "molecular factors of resistance". The discovery of these
factors will help oncologists in triaging patients to receive the most beneficial therapy by
recognizing when not to give particular treatment and will be essential for reducing the
potential for harmful side effects and for avoiding the extremely high cost of modern
treatments when they can be predicted to be ineffective.
Observational Model: Case-Only, Time Perspective: Prospective
Biomarkers changes in patients that have been exposed to chemotherapy
Mark Basik, MD
Segal Cancer Centre, Jewish General Hospital
Canada: Jewish General Hospital Institutional Review Board
|John H. Stroger, Jr. Hospital of Cook County||Chicago, Illinois 60612-9985|