Study links breast cancer spread, gene

The Baltimore Sun

Researchers have identified a gene that appears crucial to the spread of breast cancer while making the disease resistant to chemotherapy.

The discovery, if confirmed in further studies, could pave the way for new drugs that could save lives by keeping the disease from invading the lungs, liver or other vital organs, the places where it kills.

"What this tells us is we can really focus on this one gene," said Dr. Yibin Kang, a Princeton University molecular biologist and lead author of a study being published today in the journal Cancer Cell. "I will be betting this one will be a major target."

A striking 40 percent of breast cancer patients studied were found to have this "bad-prognosis" gene, meaning that any new therapies could potentially help a lot of people stricken with particularly deadly forms of the disease.

Dr. Ben Park, a Johns Hopkins breast cancer researcher who was not involved with the study, praised the work done by Kang and his colleagues and noted that a discovery like this would be game-changing if it is borne out.

But he cautioned that the research - using samples from human breast cancer tumors and checking the information through experiments with laboratory mice - is not ready for use in clinical practice and might not be for many years, if at all.

"This is not prime time yet and it may never get to prime time," Park said. "This is the type of stuff that gives one hope we're making progress in the war on breast cancer. But it's the beginning and hypothesis-generating ... not hypothesis-proving."

Researchers have long believed that solving metastasis could be a key to solving breast cancer because localized breast cancer rarely kills. The five-year survival rate for localized breast cancer is 98 percent.

But when, at diagnosis, the cancer has metastasized, or spread to other parts of the body, the five-year survival rate is just 27 percent.

"Over 99 percent of [women who die from breast cancer] die because they have metastatic disease," Kang said. "The tumor in the breast doesn't kill the patient. It's the tumor that spreads to the liver or lung or brain that kills the patient."

The gene discussed in the journal article is called "metadherin," or MTDH. It appears to make tumor cells sticky so they adhere to blood vessels in distant organs, allowing them to penetrate surrounding tissue. The gene is found normally in the lungs and in bone marrow, but is not typically found in breast tissue, researchers said. Researchers found that many copies of the gene were present in a high percentage of aggressive and deadly cancers.

"This is likely to have implications beyond breast cancer," said Dr. Michael Reiss, another of the paper's authors and director of the breast cancer research program at the Cancer Institute of New Jersey. "Very often these processes are not unique to one cancer type."

Kang said his research shows the gene also might play a role in 20 percent of prostate cancer patients.

Most of the talk about breast cancer and genes has focused on the BRCA1 and BRCA2 genes, mutations of which increase the likelihood that their carriers will develop breast or ovarian cancer.

The new gene is different. This wouldn't aid doctors in preventing cancer from developing. It would predict whether the patient's breast cancer is likely to spread and kill.

Among the next steps for researchers are larger trials to see whether the MTDH gene and its apparent role in the spread of breast cancer hold true. At the same time, Kang and Reiss hope that drug companies will fund research into therapies that could turn off the gene in these cancer patients.

Park said he would be surprised if further research showed that so many cases of deadly cancer could be traced back to one gene. He has seen a lot of studies in the past claiming to "be the biggest thing since sliced bread" that, in the end, don't "pan out."

"To say you can actually prognosticate someone's breast cancer recurrence by a single gene is a little bit of a hard sell in this business," he said. "Biology tends to be more complicated [in the body] than it is in the laboratory."

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