Next-generation sequencing-based testing can identify human epidermal growth factor receptor 2 (HER2) mutations in breast cancer not detected using standard HER2 testing. Many of these somatic mutations drive tumor growth and may respond to HER2-targeted drugs typically reserved for HER2-positive or overamplifying patients, say the authors of a study published online Dec. 7 in Cancer Discovery in conjunction with a presentation at the San Antonio Breast Cancer Symposium. “HER2 somatic mutation is an alternative mechanism to activate HER2 in breast cancer and they validate HER2 somatic mutations as drug targets for breast cancer treatment,” write the researchers, led by Ron Bose, M.D., Ph.D., from Washington University (St. Louis). Using DNA samples from eight breast cancer sequencing studies, the researchers identified and functionally characterized 13 HER2 somatic mutations in 25 HER2 gene amplification-negative breast cancer patients. Seven of the 13 mutations drove cancer growth with most of these mutations responding well to the anti-HER2 drugs lapatinib and trastuzumab or to neratinib, a newer anti-HER2 drug in clinical trials. Sounding caution, however, the researchers acknowledge that some of the mutations did not drive tumor growth and would likely not respond to HER2-targeting drugs. “If we can identify mutations that we can act […]
Next-generation sequencing-based testing can identify human epidermal growth factor receptor 2 (HER2) mutations in breast cancer not detected using standard HER2 testing. Many of these somatic mutations drive tumor growth and may respond to HER2-targeted drugs typically reserved for HER2-positive or overamplifying patients, say the authors of a study published online Dec. 7 in Cancer Discovery in conjunction with a presentation at the San Antonio Breast Cancer Symposium.
“HER2 somatic mutation is an alternative mechanism to activate HER2 in breast cancer and they validate HER2 somatic mutations as drug targets for breast cancer treatment,” write the researchers, led by Ron Bose, M.D., Ph.D., from Washington University (St. Louis).
Using DNA samples from eight breast cancer sequencing studies, the researchers identified and functionally characterized 13 HER2 somatic mutations in 25 HER2 gene amplification-negative breast cancer patients. Seven of the 13 mutations drove cancer growth with most of these mutations responding well to the anti-HER2 drugs lapatinib and trastuzumab or to neratinib, a newer anti-HER2 drug in clinical trials. Sounding caution, however, the researchers acknowledge that some of the mutations did not drive tumor growth and would likely not respond to HER2-targeting drugs.
“If we can identify mutations that we can act on, that information will help us better guide treatment,” said Bose in a statement. “In this case, we don’t even have to develop new drugs against HER2 mutations. It’s just a matter of finding the patients.”
The researchers estimate that undetected HER2 mutations—rather than the HER2 amplification—may be driving tumor growth in 1.5 percent to 2 percent of all breast cancer cases, or nearly 4,000 patients annually. As a result of these findings, the researchers have launched a phase II clinical trial to test whether HER2-negative, stage IV breast cancer patients will benefit from anti-HER2 drugs.
