Individualized HER2 Breast Cancer Treatments

Approximately 8,000 to 10,000 women die each year from HER2 positive breast cancer. Knowing in advance how to treat an individual with HER2 breast cancer, when to treat with the commonly prescribed drug Herceptin or use a different form of treatment, could potentially save thousands of lives each year.

Researchers in Scotland have developed a new method to predict a breast cancer patient's response to the cancer drug Herceptin. In doing so, they have moved science one step closer to individualized HER2 breast cancer treatments.

The research was done by a team from the Breakthrough Breast Cancer University of Edinburgh Research Unit at the Western General Hospital, Edinburgh, Scotland. Their findings were published on July 28, 2009, in the journal Cancer Research.

Herceptin Use in Breast Cancer
About one in every three cases of breast cancer are HER2 positive, meaning the cancer tests positive for the protein human epidermal growth factor receptor-2. HER2-positive breast cancers are more aggressive than other forms of breast cancer and are less responsive to hormone therapies.

The drug Herceptin is designed to specifically target HER2 cells. The medication, used alone or in combination with other therapies, kills the HER2 cancer cells and reduces the chance of breast cancer recurrence by up to 50 percent. While Herceptin has been effective in most cases, some HER2 breast cancer patients do not respond to the drug or become resistant to it.

Studies on Individual Response to Herceptin
The research team, led by pathologist Dr Dana Faratian, set out to discover why some women are resistant to Herceptin. To do so, they developed a mathematical model to represent the interactions of molecules involved in breast cancer. This computer model led to the discovery that the amount of the protein PTEN in a cell is related to anit-HER2 therapy resistance. The team then verified their mathematical findings through tests on breast cancer cells grown in the laboratory.

The research team studied 122 samples of breast cancer tumors treated with Herceptin. They found there is a definite link between the level of PTEN and overall survival. Breast cancer patients who had high levels of PTEN in their tumors survived approximately 22 months longer than those with lower levels.

PTEN (phosphatase and tensin homolog) is a protein encoded by the PTEN gene. The gene is a known tumor suppressor, using its protein to signal cells to stop dividing and undergo apoptosis (programmed cell death), thus preventing the uncontrolled growth that leads to tumor formation. The mutation of this gene, which reduces the function of its protein, is associated with many forms of cancer, including breast cancer.

The Next Step in Individualized Breast Cancer Treatments
The research team's next step is to devise a test to detect PTEN levels in cancer patients before deciding to use Herceptin therapy.

Said Dr. Faratian, "This work is a major step forward because despite Herceptin benefiting thousands of women, it does not work for some patients.

"The impact of this new approach could be huge. It shows we can use computer modeling to answer clinical questions and potentially refine the treatment of women with breast cancer," she said.