A gene involved in setting cholesterol levels may also determine whether breast cancer spreads to other parts of the body.
A variant of the PCSK9 gene drives the spread of breast cancer, but a lab-made antibody already approved to treat high cholesterol may help stop the exodus, researchers report December 9 in Cell.
For years, researchers have been examining normal tissue and breast cancer tumors that had spread to other parts of the body trying — and failing — to find mutations that spur the migration, says oncologist and cancer biologist Sohail Tavazoie of the Rockefeller University in New York City. Wenbin Mei, a cancer biologist in Tavazoie’s lab, wondered if inherited genetic variants — instead of mutations that happen in tumors — might give cancer cells wanderlust.
Mei and colleagues found that a variant of the PCSK9 gene was associated with the metastasis, or spread, of breast cancer. In a large study in Sweden, people who inherited two copies of the spread-associated variant have a 22 percent risk of developing metastasis within 15 years of their original diagnosis, the researchers found. That compares with a 2 percent risk of spread among people who inherited one or no copies of the variant. Reexamination of results of three other studies showed that breast cancer patients who inherited two copies of the variant had lower survival rates than patients who didn’t.
About 70 percent of people of European or African descent have two copies of the variant. Nearly all Asians, especially East Asians, have two copies, Mei says. And the variant is also very common in South America.
PCSK9 was originally discovered because it helps raise cholesterol levels. An experiment in mice to lowerer cholesterol with statin drugs did not prevent cancer spread, Mei and colleagues discovered, suggesting the variant must be doing something else to spur metastasis.
A protein made by the pathogenic version of PCSK9 removes another protein that acts as a brake on two genes that spur cancer spread, mouse experiments revealed. An antibody, already approved as a treatment for high cholesterol, prevents the PCSK9 protein from removing the brake, and “we see that we get a reduction in breast cancer metastasis,” Tavazoie says. “It’s not a cure, it’s a reduction.”
Using the antibody earlier, perhaps even before the onset of cancers, may produce better results for people with two copies of the variant, Tavozoie says. Clinical trials may determine whether the antibody could help prevent cancer spread or improve survival in patients who already have metastatic breast cancer.
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