ESMO: Cancer Whole-Genome Scanning Allows Better Personalization of Metastatic Breast Cancer Therapies

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(ChemotherapyAdvisor) – Whole-genome scanning for genetic mutations in breast tumor tissue is viable and allows identification of patients who might benefit from targeted therapies that would otherwise go unconsidered, according to a study proffered at the European Society for Medical Oncology (ESMO) annual meeting in Vienna, Austria.

Genetic testing is widespread for breast cancer and other cancer patients and plays a key role in personalizing treatment with targeted therapies. But genetic testing in clinical practice is typically narrowly-focused on particular alleles, noted Fabrice André, MD, PhD, of the Institute Gustave Roussy, Villejuif, France. 

"In the future, we think that whole-genome approaches to genomic testing of cancer will be the standard of care since they provide a broad picture of genomic alterations and an easy way to test biomarkers," Dr André said. 

In the SAFIR01 trial, Dr André's team prospectively analyzed metastatic breast tumor genomes from 248 patients, using array CGH (aCGH) and Sanger sequencing to detect genetic mutations, amplifications and deletions. Findings were used to guide selection of targeted therapies for study participants; therapies were selected on the basis of genomic analysis for 172 patients.

“Very rare” and unexpected genome aberrations were detected in approximately 20% of those patients, Dr. André reported.

"When results from the SAFIR01 trial and its pilot phase are pooled, 18 out of 48 patients treated according to whole genome analysis presented evidence of antitumor activity," Dr André said. 

Whole-genome testing can identify not only common cancer genes, but rare ones, Dr. André said, allowing oncologists “to quantify the level of genomic instability, and to detect whether driver mutations are associated with genomic alterations involved in resistance to targeted agents.” 

Whole-genome testing also obviates the need to develop new biosassays for each gene target that is identified, Dr. André noted.

"The main message is that whole genome approaches can be delivered in the context of daily practice in large cohorts, allowing us to identify targets that can be inhibited in a high proportion of patients, leading to anti-tumor effects," Dr André said. “This study suggests that time has come to bring personalized medicine to the cancer field.” 

Commenting on the paper, Peter Dubsky, MD, of the Department of Surgery at the Medical University of Vienna (who was not involved in the study) commended the research team's work but cautioned that metastatic tumor biopsies will not always be feasible. Dr. Dubsky asked if whole-genome testing of primary tumor tissue might not be sufficient for identifying drug targets in cancer genomes.

The study was funded by the French National Cancer Institute. 

Abstract (#LBA13_PR)

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