Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First large scale trial of whole-genome cancer testing for clinical decision-making reported

01.10.2012
Study opens a new door to more personalized treatment of advanced breast cancer

For the first time, researchers have conducted a large trial in which they tested the entire genome of individual breast cancers to help personalize treatment. They released their findings at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

In recent years, a number of drugs have been developed that target specific genetic alterations in cancer. To choose which of these drugs are suitable for individual patients, some genetic testing is performed. "In most of these cases, these genetic testing approaches only analyze a limited number of genes," said study author Dr Fabrice André from Institute Gustave Roussy, Villejuif, France.

The theoretical benefit of whole genome testing is that this approach can identify both frequent and rare unexpected genomic events. "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," Dr André said.

In terms of healthcare delivery and policy, developing whole-genome approaches also means new bioassays do not need to be designed for each new target discovered in cancer.

In the SAFIR01 trial, Dr André and colleagues developed a program where the entire genome from a biopsy of a metastatic lesion was analyzed prospectively for individual patients with metastatic breast cancer. They used array CGH (aCGH) and Sanger sequencing to identify the genetic alterations in the metastatic tissue, which allowed them to identify which genes were mutated, amplified or deleted. This genomic information was prospectively used to propose different targeted therapies. The study was conducted and sponsored by UNICANCER and funded by the French National Cancer Institute.

As of 23 September 2012, biopsies had been performed in 402 breast cancer patients, including 26 patients for whom analyses are ongoing. Of those, a genomic result could be generated in 276 patients, including whole genome analysis in 248. A genomic alteration "targetable" by an anticancer drug was found in 172 of those patients, Dr André said. Interestingly, around 20% of the patients presented a very rare and sometimes unexpected genomic alteration, highlighting the need for whole genome approaches.

"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. This study suggests that time has come to bring personalized medicine to the cancer field," Dr André said.

Although only a minority of patients needed an investigational agent since the biopsy, 26 patients so far received a targeted agent matched to the genomic alteration. The goal is to reach more than 80 patients treated with a targeted agent.

"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.

"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 concluded.

Commenting on the data, Dr Peter Dubsky, Associate Professor of Surgery at the Medical University of Vienna (who was not involved in the study) said: "SAFIR01 is a remarkable accomplishment that has moved personalized molecular dissection of breast cancer into a setting that is, in principle, transferable into clinical practice."

"The investigators have been able to analyze large parts of the individual breast cancer genome and have furthermore been successful in identifying molecular alterations with a good chance of responding to specific treatments," Dr Dubsky said. "In other words, they create the possibility of identifying 'drug-able' targets in women showing progression of metastatic disease. Both the technical achievement and the organizational and ethical hurdles overcome by the French consortium represent dedicated and clinically relevant research at its best."

"The French consortium has opened a new door to more personalized treatment of advanced breast cancer," Dr Dubsky said. "Clinical research will have to address the clinical utility of such approaches compared to current standards."

Several questions remain to be discussed, Dr Dubsky said: "The biopsy of metastases (especially in order to obtain high-quality DNA) is not always feasible, is expensive and may lead to additional morbidity. Given the recent insights from next generation sequencing techniques, it is worth asking how relevant tissue from the metastatic site is. In other words, in the future would fresh tissue from the primary be sufficient to screen for drug targets?"

"It is also important to mention that the definition of breast cancer subtypes is already a clinical reality in the treatment of advanced and early disease. Oncologists are able to dissect breast cancer subtypes based on hormone receptors, the expression of Her2-neu and markers for differentiation and proliferation of the tumor. Whole genome approaches will have to be compared to this current gold standard in terms of their clinical utility."
Recently, the targeting of the PI3K/mTOR pathway using mTOR inhibitor in combination with exemestane has lead to a major improvement of clinical benefit in women with metastatic hormone receptor-positive and Her2neu negative breast cancer, Dr Dubsky said. "It is noteworthy that this target was based on molecular research. The patients to benefit from this new treatment combination however were selected clinically: women who had developed endocrine resistance to prior endocrine treatment were selected and showed a remarkable clinical benefit rate. The clinical trials providing this evidence were successful without individual molecular identification of the treatment target."

Related presentation at ESMO 2012
Prospective trial (REMAGUS04) evaluating the use of gene expression arrays to select neoadjuvant chemotherapy for operable breast cancer shows that the approach quantifies gene expression accurately and validates predictive value of DLD30 and immune signatures (abstract 245O).

ESMO PRESS OFFICE | EurekAlert!
Further information:
http://www.esmo.org

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>