Precision Medicine for Metastatic Breast Cancer

Abstract

OVERVIEWGenomic studies have shown that large numbers of candidate targets are observed in breast cancer. Nevertheless, only a few of them are validated as relevant targets in clinical studies. Estrogen receptor (ER) and HER2 expressions could be associated with a level I evidence. Beyond ER and HER2, BRCA and PIK3CA mutations (when targeted with alpha-specific PI3K inhibitors) could be considered as promising targets in breast cancer since they have been associated with objective responses in phase I/II trials. In addition to these four molecular alterations, several others have shown promising results in preclinical studies and are being investigated in clinical trials. These genomic alterations include AKT1, ERBB2, and ESR1 mutations. These considerations highlight the lack of evidence for using multiplex technologies to individualize therapy in metastatic breast cancer. Sequencing multiple genes to treat metastatic breast cancer is very promising but should be done in the context of clinical trials, either to enrich phase I/II trials in patients with genomic alterations or to show medical usefulness of new biotechnologies like next-generation sequencing (NGS). Although most current approaches of precision medicine are aiming at targeting drivers, additional applications could be developed in the future. This includes the identification of DNA repair deficiencies, mechanisms of immune suppression, and identification of minority lethal subclones. Finally, one of the very promising applications of genomics for metastatic breast cancer is the identification of pathway activation or defects at the individual level. For example, gene expression and single nucleotide polymorphisms (SNP) signatures are being developed to detect kinase (such as mammalian target of rapamycin [mTOR]/CDK4) activations or DNA repair deficiencies.

Integrated Patient-Derived Models Delineate Individualized Therapeutic Vulnerabilities of Pancreatic Cancer

“…There are multiple successes attributed to precision medicine, from the current paradigm for breast cancer treatment stratification based on immunohistochemical markers (e.g. ER,PR or HER2) to the integrated genetic analysis of lung cancer that reveals multiple targets for therapeutic intervention (e.g., ALK rearrangements or EGFR mutations) (Deluche et al, 2015; Lindeman et al, 2013). Based on these and other successes, multiple clinical trials utilizing genetic information to guide patient treatment are open.…”

Precision Medicine: Steps along the Road to Combat Human Cancer

“…With further enhancements and refinements, we will develop pharmaceuticals, equipment and techniques which are less costly to research and produce, safer, and more effective. As the once-revolutionary techniques and treatments of personalized medicine take hold, the diagnosis and treatment of disease will change forever [ 24 , 25 , 26 , 27 , 28 ].…”

Overview of the CLEOPATRA Trial: Implications for Advanced Practitioners

“…Breast cancer remains the most frequent cause of cancer-related death in women, and although significant advances have been made in the treatment of breast cancer, many women still die of metastatic breast cancer (Ferlay, 2010). Each metastatic breast cancer presents a specific molecular profile and molecular mechanism of cancer progression, and although a large number of candidate targets for breast cancer treatment have been elucidated through genomic studies, only a few of them are validated as relevant and effective targets in clinical studies (Deluche, Onesti, & Andre, 2015).…”