Story URL: http://news.medill.northwestern.edu/chicago/news.aspx?id=209156
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Courtesy of NHGRI

Genetic signatures of breast cancers identified by the new research. Findings show that Basal-like breast cancers (center) are more genetically similar to ovarian cancer (right) than to other breast cancers (left). This could change the way cancers are treated.


Epic genetic analysis of breast cancers sheds new light on potential treatments

by Corinne Chin
Oct 17, 2012


Identifying four genetic subtypes of breast cancer could guide doctors toward new treatment strategies, according to researchers involved in a new government study.

The findings, part of the most comprehensive breast cancer study in history, will guide new research into more targeted, and hopefully effective, treatments. Currently, breast cancer afflicts one in eight American women, the most common cancer affecting them.

Clinical trials examining the effects of existing ovarian cancer drugs on one type of breast cancer are already underway as a result of the study.

The Cancer Genome Atlas (TCGA) Research Network, a collaboration of more than 150 researchers across the world, completed a comprehensive genetic analysis of 825 tumor samples. The study,  published this month in the journal Nature, was funded by the National Cancer Institute and National Human Genome Research Institute.

“The different types of breast cancer were already known, but this was the largest magnitude study ever of the genomics,” said Brad Ozenberger, TCGA program director for NHGRI. “Each specimen got the full comprehensive genomic analysis that TCGA does. Basically, it created a hugely rich database of what constitutes the inner workings of breast cancer.”

In the study, researchers completed full genetic sequencing on four primary classes of tumors: HER2-enriched, Luminal A, Luminal B and Basal-like. The genomic information revealed that Basal-like tumors seem to share more genetic features with high-grade ovarian cancer than with other breast cancers.

Basal-like tumors are also known as “triple negative” tumors, because their growth is not spurred by estrogen or progesterone hormones, or the HER2 protein, as other classes of breast cancers are. Prior to this study, treatments for these tumors have been limited to non-targeted chemotherapy.

“The importance of this clinically is the identification of specific cellular targets that we can attack,” said Dennis Citrin, a medical oncologist at the Midwestern Regional Medical Center of Cancer Treatment Centers of America. “We already have Tamoxifen for estrogen receptors and Herceptin to target HER2. Basal-like cancers have no specific cellular target. This type of study helps provide a rational basis for using those [chemotherapy] drugs which are already effective.”

However, the new research shows that simply categorizing a tumor as HER2-enriched will not always predict how the patient will respond to therapy.

“When we look at the genomics, there are two categories, and we can predict from the HER2 signature which ones will respond to [chemotherapy drug] Herceptin,” Ozenberger said. “TCGA’s goal is not actually to make discoveries that can go right into the clinic, but in this case, that was a pretty important finding.”

The full TCGA findings are available to pharmaceutical companies to develop new therapeutic approaches over the next several years. According to Ozenberger, a pipeline of additional findings will be published over the next two years.

"I would imagine in a couple of years, some of these results will propagate into routine care,” Ozenberger said.

Meanwhile, as genome sequencing is becoming quicker, easier and more affordable, more genetically targeted treatments will become a reality. Some clinics already offer genetic sequencing of tumors to help target treatments, but this is not a routine test nor is it covered by many insurance policies. Ozenberger expressed hope that such tests will eventually be fully integrated into the healthcare system.

“It’s not going to be next week or next month, but definitely in the foreseeable future, there’s going to be a real benefit,” Citrin said.

Citrin is already using some genetic tests to categorize and treat patients, including tests to identify estrogen receptor-positive patients who may not need chemotherapy, instead relying only on endocrine therapy to cut off the estrogen that feeds tumor growth.

“I just had a patient" who benefitted from the tests, said Citrin. “This commercially available test came out of original research that was published [years ago]. It certainly takes time for the basic science research to have real clinical applications.”

Researchers are optimistic that current research will bring similarly tangible advances in genetic medicine.

“There is a big change about to happen and it’s really just in its infancy,” Ozenberger said. “This is a groundswell of promising data and new promise in the fight against cancer. It’s a very hopeful time.”