Breast cancer 'road map' could point way to cure

Researchers have for the first time identified four genetically distinct types of breast cancer and determined that one type has more in common with an aggressive form of ovarian cancer than the other breast cancers.

The study, published online on Sunday in the journal Nature, 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. Breast cancer kills more than 35,000 women a year in the United States.

The 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.

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."

Cancer Genome Atlas

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.

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 basal cells form a scaffolding for milk duct cells. Such cancers are often called triple negative but the study researchers call them basal-like.

Basal-like cancers are most frequent in younger women, in blacks and in women with breast cancer genes BRCA1 and BRCA2.

And, the researchers report, their genetic derangements make these cancers a much closer kin of ovarian cancers than of other breast cancers. Basal-like breast cancers also resemble squamous cell cancer of the lung.

"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."

Anthracyclines, Ellis said, "are the drugs most breast cancer patients dread because they are associated with heart damage and leukemia."

A new type of drug, PARP inhibitors, that seems to help squelch ovarian cancers, should also be tried in basal-like breast cancer, Ellis said.

Two other types of breast cancer, accounting for most cases of the disease, arise from the luminal cells that line milk ducts. These cancers have proteins on their surfaces that grab estrogen, fueling their growth. Just about everyone with estrogen-fueled cancer gets the same treatment. Some do well. Others do not.

'Getting at the roots'

The genetic analysis divided luminal cancers into two distinct subtypes. The luminal A subtype had good prognoses while luminal B did not, suggesting that perhaps patients with luminal A tumors might do well with just hormonal therapy to block estrogen from spurring their cancers while luminal B patients might do better with chemotherapy in addition to hormonal therapy.

"We are really getting at the roots of these cancers," he said.

After basal-like cancers, and luminal A and B cancers, the fourth type of breast cancer is what the researchers called HER2-enriched. Breast cancers often have extra copies of a gene, HER2, that drives their growth. A drug, Herceptin, can block the gene and has changed the prognosis for these patients from one of the worst in breast cancer to one of the best.

Yet although Herceptin is approved for every breast cancer patient whose tumor makes too much HER2, the new analysis finds that not all of these tumors are alike. The HER2-enriched should respond readily to Herceptin; the other type might not.

The only way to know is to do a clinical trial, and one is already being planned. Herceptin is expensive and can occasionally damage the heart. "We absolutely only want to give it to patients who can benefit," Perou said.

For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a massive undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there may have to be dozens of drug studies, each focusing on a different genetic change.