From Our 2012 Archives
Existing Breast Cancer Drugs May Help More Women
By Charlene Laino
Reviewed by Laura J. Martin, MD
Dec. 7, 2012 (San Antonio) -- Current screening tests may miss as many as 1 in 50 women with breast cancer who would benefit from treatment with highly effective breast cancer drugs.
At issue is HER2-positive breast cancer, an aggressive form of the disease that was difficult to treat until the FDA approved the drug Herceptin in 1998. Herceptin revolutionized the treatment of HER2-positive breast cancer, reducing the risk of recurrence and prolonging lives.
Since then, two other drugs, Tykerb and Perjeta, have been approved for the treatment of HER2-positive breast cancer. Others are in the pipeline.
The new study involved 1,500 women found to be HER2-negative on routine HER2 testing. Genetic analysis showed 25 had HER2 mutations.
"These mutations would be missed by current HER2 testing," says researcher Ron Bose, MD, PhD, of the Washington University School of Medicine in St. Louis.
"As a result, the women would not receive potentially lifesaving treatment with HER2 targeted drugs," he says.
The findings were presented at the San Antonio Breast Cancer Symposium (SABCS) here and published online in the journal Cancer Discovery.
A patient must have more than the normal two copies of the HER2 gene to be classified as HER2-positive. About 20% to 25% of women with breast cancer fall into this category. The excess HER2 drives tumor growth.
The HER2 mutations stimulate tumor growth in a different way. "Many turn on HER2 activity in an inappropriate manner, which probably results in abnormal, unregulated HER2 signaling. This is likely driving the cancer cell," Bose says.
The genetic analyses revealed that 1.5% to 2% of all breast cancer patients have these genetic mutations. With about 230,000 new cases of breast cancer in the United States each year, even this modest percentage translates into more than 4,000 patients per year.
Will HER2 Targeted Drugs Help?
In laboratory tests, Herceptin and Tykerb killed many of the mutant cells. Two mutations that were resistant to Tykerb responded well to neratinib, an experimental anti-HER2 drug.
Some mutations were found to be "silent," meaning they did not drive tumor growth and therefore would likely not respond to anti-HER2 drugs, Bose says.
Now the researchers have launched a study in which women will be screened for HER2 mutations. Those who have the mutations will be given neratinib. Doctors will follow the women to see if the drug is effective and safe.
Asked if the high cost of genetic analysis would prohibit its routine use, Bose says that it is increasingly being used in other forms of disease, such as lung cancer.
If trial results show that attacking the newfound mutations can prevent recurrences and save lives, then gene tests -- and their cost -- will quickly be accepted as part of the standard of care.
"In the future, we will probably be talking about panels of relevant genes that will need to be sequenced in breast cancer," he says.
SABCS co-director Kent Osborne, MD, a breast cancer specialist at Baylor College of Medicine in Houston, says he believes even more mutations that drive breast cancer growth will be discovered in coming years.
And it's likely the newly discovered mutations may promote growth of other types of tumors as well, he says.
Osborne says he would also like to see studies testing whether the anti-HER2 drugs already on the market benefit women with the mutations.
SOURCES: San Antonio Breast Cancer Symposium, San Antonio, Texas, Dec. 4-8, 2012. Bose, R. Cancer Discovery, published online Dec. 7, 2012. Ron Bose, MD, PhD, Washington University School of Medicine, St. Louis. Kent Osborne, MD, Baylor College of Medicine, Houston.
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