Scientists Discover How BRCA1 Gene Causes Cancer

From Breastcancer.org

What breastcancer.org says about this article

The study reviewed here seems to have figured out how abnormal BRCA1 genes (BReast CAncer gene 1) lead to breast cancer. When BRCA1 genes are healthy, they fix DNA breaks (protein strands that make up chromosomes and genes). When BRCA1 genes are abnormal, they can't fix DNA breaks, specifically breaks in a gene called PTEN. PTEN genes stop cancer tumors from growing. If a PTEN gene has a DNA break that isn't repaired, cancer cells have nothing to stop them and grow rapidly.

DNA breaks happen all the time as cells in the human body grow and multiply. In most cases, the cells realize a mistake has happened and fix the problem. But if a "fixer" gene such as BRCA1 is abnormal, there is no way for the cells to fix the mistake. As researchers have learned more about the role of specific genes and proteins, they have developed a group of medicines called targeted therapies that tell genes and proteins to do specific things to stop cancer growth. Herceptin, Tykerb, and Avastin are all targeted therapies.

The results of this study may help researchers develop new targeted therapies to repair breaks in the PTEN gene. This could help women diagnosed with what's called triple-negative breast cancer (estrogen-, progesterone-, and HER2-negative). Right now, this type of breast cancer has limited treatment options because current hormonal and targeted therapies don't work.

According to statistics from the National Cancer Institute (NCI), about 15% of all breast cancers are triple negative. Young African American women are more likely than women of other ethnicities/races to be diagnosed with triple-negative breast cancer.

Stay tuned to breastcancer.org for the very latest news on research that may lead to new breast cancer treatments.

Last Updated: 2007-12-11 11:17:09 -0400 (Reuters Health)

By Julie Steenhuysen

CHICAGO (Reuters) - Mutations in the BRCA1 breast cancer gene appear to be linked with the loss of a protein important for putting the brakes on cell growth, a finding that could lead to new therapies, researchers said on Sunday.

The breakthrough could lead to more effective therapies for women with an aggressive and especially deadly cancer known as triple-negative that does not respond to current advanced drugs, the researchers said.

"It doesn't have a good target for therapy at this point," said Dr. Ramon Parsons of Columbia University Medical Center in New York, who worked on the study.

Scientists have known for more than a decade that women with certain alterations in the BRCA1 gene were at high risk for breast cancer. What they have not understood is exactly how a mutation in this gene leads to cancer.

Researchers at Columbia, working with at team at Sweden's Lund University, now believe mutations in the BRCA1 gene can leave cells incapable of repairing routine DNA damage. When such damage occurs in a protein called PTEN, which regulates the growth of cells, cell growth is unchecked and tumors form.

Women with faulty copies of BRCA1 or BRCA2 have a 50 to 85 percent chance of getting breast cancer. Mutations in these genes account for 5 to 10 percent of breast cancer cases.

Most breast tumors are called estrogen-receptor positive, because they are fuelled by the hormone estrogen. About 20 percent are HER2-positive, because a protein called HER2 is involved. A third type is driven by the hormone progesterone.

These types of cancer have good treatments.

Then there are basal-like or triple-negative tumors, so named because they lack estrogen, progesterone or HER2 receptors needed for most breast cancer drugs to work.

UNCHECKED GROWTH

"The basic idea is that BRCA1 is a repair enzyme that is involved in coordinating the repair of double strand DNA breaks," said Parsons said in a telephone interview.

"When it is mutated, it is no longer present in a cell. If a cut occurs in PTEN, there is no way for this cell to fix it," said Parsons, whose study was published in Nature Genetics.

"It is like cutting the brake cable on a car," he said. "If PTEN is broken, you turn on a pathway that tells the cell to grow. It tells the cell to start dividing. It tells the cell, 'don't die.'"

Parsons said loss of the protein PTEN is how breast cancer gets started in women who have inherited the BRCA1 gene mutation.

His team made the connection between BRCA1 and PTEN by searching for chromosome breaks within the PTEN gene.

They scanned 34 biopsies taken from women with BRCA1 tumors. The PTEN gene had been split in two, but inadequately repaired in about one-third of the cancers. In some cases, entire sections of the gene were missing.

They said these chromosomal mistakes trace back to the tumor's lack of BRCA1, which is charged with cell repair. He estimates that about 50 percent of BRCA1 breast cancers harbor mutated PTEN.

"These tumors have very high frequency loss of the PTEN protein," Parsons said. In breast cancers from women with normal BRCA1, they rarely found large mutations in PTEN.

"A lot of drug companies are working on this. There is reasonably good hope that this approach will improve therapy for patients," Parsons said.

Basal-like breast tumors are also found in 10 to 20 percent of women whose cancer was not caused by BRCA1 or another gene. The researchers found PTEN is lost in most of these breast tumors as well.