In findings that are fundamentally reshaping the scientific understanding of breast cancer, researchers have identified four genetically distinct types of the cancer. And within those types, they found hallmark genetic changes that are driving many cancers.
These discoveries are expected to lead to new treatments with drugs already approved for cancers in other parts of the body and new ideas for more precise treatments aimed at genetic aberrations that now have no known treatment.
The study, published online on Sunday in the journal Nature, is the first comprehensive genetic analysis of breast cancer, which kills more than 35,000 women a year in the United States. The new paper, and several smaller recent studies, are electrifying the field.
"This is the road map for how we might cure breast cancer in the future," said Dr. Matthew Ellis of Washington University, a researcher for the study.
Researchers and patient advocates caution that it will still take years to translate the new insights into transformative new treatments. Even within the four major types of breast cancer, individual tumors appear to be driven by their own sets of genetic changes. A wide variety of drugs will most likely need to be developed to tailor medicines to individual tumors.
"There are a lot of steps that turn basic science into clinically meaningful results," said Karuna Jaggar, executive director of Breast Cancer Action, an advocacy group. "It is the ?stay tuned? story."
The study is part of a large federal project, the Cancer Genome Atlas, to build maps of genetic changes in common cancers. Reports on similar studies of lung and colon cancer have been published recently. The breast cancer study was based on an analysis of tumors from 825 patients.
"There has never been a breast cancer genomics project on this scale," said the atlas? program director, Brad Ozenberger of the National Institutes of Health.
The investigators identified at least 40 genetic alterations that might be attacked by drugs. Many of them are already being developed for other types of cancer that have the same mutations. "We now have a good view of what goes wrong in breast cancer," said Joe Gray, a genetic expert at Oregon Health & Science University, who was not involved in the study. "We haven?t had that before."
The study focused on the most common types of breast cancer that are thought to arise in the milk duct. It concentrated on early breast cancers that had not yet spread to other parts of the body in order to find genetic changes that could be attacked, stopping a cancer before it metastasized.
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The study?s biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are present in the deepest layer of the skin. These breast cells form a scaffolding for milk duct cells.
This type of cancer is often called triple negative and accounts for a small percentage of breast cancer.
But researchers found that this cancer was entirely different from the other types of breast cancer and much more resembles ovarian cancer and a type of lung cancer.
"It?s incredible," said Dr. James Ingle of the Mayo Clinic, one of the study?s 348 authors, of the ovarian cancer connection. "It raises the possibility that there may be a common cause."
It raises the possibility that some women could be treated with less toxic drugs for ovarian cancer rather than with a type of drug, anthracyclines, which has harsh side effects.
Anthracyclines, Ellis said, "are the drugs most breast cancer patients dread because they are associated with heart damage and leukemia."
Such cancers are often called triple negative but the study researchers call them basal-like.
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