Wash. U. Doctors Decode Breast Cancer DNA -- And Discover It's Way More Complicated Than They Thought

click to enlarge All forms of breast cancer are not the same. - image via
All forms of breast cancer are not the same.

As any woman -- or any casual viewer of boob-centric photos, including Riverfront Times slide shows -- knows, all breasts are not alike. This, it turns out, is also true genetically, and, unfortunately, for breast cancer.

After spending several years sequencing the DNA from 50 breast cancer patients, doctors at Washington University School of Medicine have come to one major conclusion: Developing a cure for breast cancer is going to be way harder than they thought.

After sequencing more than 10 trillion DNA bases (which involved repeating the sequencing of each patient's DNA 30 times to get the most accurate reading) and comparing healthy cells to cancer cells, the doctors discovered more than 1,700 different mutations, most of which were patient-specific. That is to say, most patients have their own particular form of breast cancer.

"Cancer genomes are extraordinarily complicated," said Matthew Ellis, a Wash. U. professor and the lead investigator in the experiment, in a press release. "This explains our difficulty in predicting outcomes and finding new treatments."

All the patients in the study had estrogen-receptor-positive breast cancer in which cancer cells grow by using receptors to bond to the hormone estrogen. Normally, patients with this sort of breast cancer receive estrogen-lowering drugs before they begin treatment. This is supposed to slow tumor growth, but only about half the patients in the study responded.

The news from the sequencing was not entirely bad. The research team confirmed earlier findings that there are two mutations that are more common than others: PIK3CA, which was present in 40 percent of the patients, and TP53, which appeared in 20 percent.

In addition, the Wash. U. team found another mutation, MAP3K1, which appeared in ten percent of the patients, and which allowed cells that would ordinarily die to continue living. There were 21 other mutated genes that appeared in two or three patients.

"To get through this experiment and find only three additional gene mutations at the 10 percent recurrence level was a bit of a shock," Ellis said. But, he added, "Breast cancer is so common that mutations that recur at a 5 percent frequency level still involve many thousands of women."

However, the scientists also discovered that some mutations in the breast cancer patients also showed up in patients with other types of cancer -- cancer for which treatments already exist. "You may find the rare breast cancer patient whose tumor has a mutation that's more commonly found in leukemia, for example," Ellis said. "So you might give that breast cancer patient a leukemia drug."

In the future, Ellis hopes that doctors will be able to customize breast cancer treatment by sequencing a patient's genes in advance in order to determine the best course of treatment. And although this round of gene sequencing offered no insights into a one-drug-fits-all treatment for breast cancer patients, Ellis said it at least gave the scientists an idea of the scope of the problem they are dealing with.

"It's not like looking into a telescope and wondering how far the universe goes," he said. "Ultimately, the universe of breast cancer is restricted by the size of the human genome."

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