Classifying breast cancer into categories promises better therapies

LOS ANGELES - Researchers have found a way to classify breast cancer tumors into 10 distinct categories ranging from very treatable to extremely aggressive, a major step on the way to the long-sought goal of precisely targeting therapies for pati...

LOS ANGELES - Researchers have found a way to classify breast cancer tumors into 10 distinct categories ranging from very treatable to extremely aggressive, a major step on the way to the long-sought goal of precisely targeting therapies for patients.

The new categories, described in a study released Wednesday, should help scientists devise fresh approaches to treat some of the cancers and could spare many women the risks and pain of unnecessarily toxic treatments, oncologists said.

"If you belong to one group you'll need one therapy, and if you're in another you'll need another," said Dr. Carlos Caldas, a breast cancer geneticist at the University of Cambridge who helped oversee the research. For some women, he added, tumor typing might indicate that traditional chemotherapy isn't warranted at all.

"A lot of women are being overtreated," he said. "Can we spare them that?"

The study, published by the journal Nature, is the first of many expected in the coming months that will use genetic clues in breast cancer tumors to help refine categories of the disease, which strikes one in eight women in the U.S.


Doctors like to say that breast cancer is not a single disease, but a range of them. But because they don't completely understand which therapies will work for a given tumor and why, they tend to err on the side of caution - administering treatments in cases in which they may provide little added benefit.

This type of research could begin to change that, experts said.

"This is going to have a huge impact on the way we think about breast cancer," said Raju Kucherlapati, a genetics professor at the Harvard Medical School who was not involved in the study. "Together with other data coming out in the next few months, I think the whole landscape of research, discovery and treatment is going to change."

Clinicians already divide tumors into a few different types, and targeted treatments are available for some flavors of the disease. For instance, women with tumors that test positive for a cancer-promoting protein called HER2 often respond well to the drug Herceptin, which isn't effective against other types of tumors.

But in a frustratingly high number of cases, scientists can't explain why one woman will respond to a given treatment and another woman won't _ even though they both might have tumors that are estrogen-receptor-positive, for example.

"It's not a very precise art," Caldas said.

Hoping to hone the process, Caldas and colleagues from Britain and Canada analyzed the genetic signatures of samples from 997 tumors, examining how aberrations in DNA turned various genes on and off. They analyzed 2 million spots on the genome, focusing on differences in the number of times a string of DNA is repeated and on small gene variations known as single nucleotide polymorphisms, or SNPs. They also looked at RNA, which helps translate DNA instructions into proteins, to gauge gene activity.

Then they correlated that data with long-term health outcomes of the women from whom the tumors were removed, establishing a link between the genetic patterns and how tumors progressed. The analysis involved complicated number-crunching and took more than five years to complete.


In the end, the research team identified 10 distinct subtypes of breast cancer. They reinforced previously known groups and were able to make further distinctions within them.

For example, they found that tumors in two of the categories had very few DNA aberrations compared with those in other groups. Tumors in one of these categories were particularly vulnerable to immune system cells, and they had one of the best profiles for prognosis.

"These tumors do have something different about them," Caldas said. And by studying them further, he suggested, researchers may discover that they respond well to novel treatments.

The team confirmed the validity of their categories by testing them in a separate group of 995 tumors.

Experts said the scale of the work was "remarkable," as Kucherlapati put it.

"The fact that they have 997 samples for discovery and 995 for validation makes it very special," he said.

Dr. John Glaspy, an oncologist at the University of California, Los Angeles' Jonsson Comprehensive Cancer Center, added that the genetic analysis also sheds light on a fundamental question: How do cancers emerge?

"It's an insight into how this whole thing works," he said. "Insight is the beginning of new treatment."


But Glaspy and others also cautioned that the discovery would not revolutionize the practice of medicine right away.

"I want to make sure people won't see this and say, 'Game over!'" said Stephen Friend, co-founder of Sage Bionetworks in Seattle, a nonprofit organization that promotes collaborative medical research. In truth, he said, the ability to match genetic signatures to long-term cancer outcomes is a sign that "the game starts."

University of British Columbia breast cancer researcher Samuel Aparicio, another leader of the study, said scientists would need to conduct clinical trials to determine whether the gene aberrations the team identified could be effectively targeted with existing drugs. The findings should also help pharmaceutical companies create new drugs to fight breast cancer, he added.

"This should be a good stimulus" for industry, he said.

Complementary research is expected shortly from the National Cancer Institute's Cancer Genome Atlas and the Wellcome Trust Sanger Institute in Hinxton, England.

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