Pathologists will be interested to learn how French researchers used whole genome sequencing of breast cancer tumors to help with diagnosis and decisions about therapy

Pathologists take note! Human whole-genome sequencing of tumors was the source of information for making treatment decisions in a recently-published study. For the first time, researchers conducted a large trial involving testing the entire genome of individual breast cancers with the aim of personalized treatment.

This is the latest example of how rapid evolution of whole-genome sequencing technology now allows researchers to evaluate clinical applications for human whole-genome sequencing. The results are promising.

The research study was conducted at the French National Institute of Health and Medical Research (INSERM). The researchers released their findings at the ESMO (European Society for Medical Oncology) 2012 Congress, held recently in Vienna, according to an ESMO press release.

New Trials Could Advance Personalized Medicine for Cancer Patients

In recent years, scientists have developed a number of drugs that target specific genetic alterations in cancer, the release noted. Scientists may perform some genetic testing to determine the suitability of drugs for individual patients.

.“In most of these cases, these genetic testing approaches only analyze a limited number of genes,” observed study author, Fabrice André, M.D., Ph.D., Research Director and Head of INSERM.

Theoretically, that’s where the benefit of whole-genome testing comes in. Not only can it identify frequent genomic events, but also rare and unexpected ones. “In addition, it allows us to quantify the level of genomic instability, and to detect whether driver mutations are associated with genomic alterations involved in resistance to targeted agents,” stated André, who is also Associate Professor at the Institut Gustave Roussy, in Villejuif, France.

Whole-Genome Sequencing as a Screening Approach

Based on previous studies, the team hypothesized that identifying the molecular mechanisms of cancer for each patient could help define which targeted therapy should be given, noted a summary of this project by the Breast Cancer Research Foundation.

In 2011-2012, the team launched a prospective clinical trial called SAFIR01 (Screening Approach for Individualized Regimen). Their aim was to identify the targets to be inhibited in patients with metastatic breast cancer.

The researchers set out to recruit 400 patients across 20 centers in France. They prospectively did a molecular analysis of biopsy samples to identify the genetic alterations in the metastatic tissue. This allowed them to identify which genes were mutated, amplified, or deleted. In turn, this allowed the researchers to prospectively propose different targeted therapies.

As of September 23, 2012, André’s team had biopsies from 402 breast cancer patients, the press release reported. The researchers determined genomic result in 276 patients. This included whole-genome analysis for 248 of the patients. In 172 of the patients, the team found a genomic alteration that was “targetable” by an anticancer drug.

Interestingly from a diagnostic healthcare angle, approximately 20% of the patients presented a very rare—and sometimes unexpected—genomic alteration. This highlights the potential for whole genome approaches to improve disease diagnosis and therapies.

Whole Genome Testing of Cancer Could Be the Future Standard of Care

“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,” declared André.

“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,” he observed. “This study suggests that [the] time has come to bring personalized medicine to the cancer field.

“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,” concluded André.

Going forward, scientists may predict that cancer diagnosis will depend less on traditional analysis of cell morphology performed on tissue that has been processed, stained, and evaluated by a pathologist using a microscope. Instead, multiplex molecular assays and whole human genome sequences will play a greater role in diagnosis, selection of appropriate therapies, and monitoring the patient’s progress.

Pathologists and clinical laboratory administrators can view this latest study as another sign that genetic testing and molecular testing are moving at a pace to become as important as traditional diagnostic methods.

—Pamela Scherer McLeod

Related Information:

ESMO 2012 Press release: First large scale trial of whole-genome cancer testing for clinical decision-making reported

The Impact of Whole Genome DNA Sequencing on Health Care

Fabrice Andre, MD, PhD

THE DARK REPORT: Whole Genome Sequencing: Is It Ready for Prime Time?