AACR 2018 Preview: Acquired HER2 Mutations and Resistance to Hormone Therapy for Breast Cancer
Posted: Friday, March 16, 2018
Some patients with estrogen receptor–positive metastatic breast cancer may acquire HER2 mutations that confer resistance to hormone therapy, and such resistance may be reversed with combination therapies that include an anti-HER2 inhibitor. These findings were presented during a media preview for the upcoming 2018 American Association for Cancer Research (AACR) Annual Meeting (Abstract 4952).
“It was surprising to discover that HER2 mutations can be acquired in the metastatic setting, suggesting these tumors evolve,” stated Nikhil Wagle, MD, senior study author and Deputy Director of the Center for Cancer Precision Medicine at Dana-Farber Cancer Institute, Boston, in an AACR press release. “Repeated sequencing of tumors can pinpoint new genetic changes that cause resistance to therapies,” he added. “This in turn can enable physicians to personalize therapy, depending on the specific genetic changes in a patient’s tumor over time.”
The investigators used whole-exome sequencing to study metastatic tumor biopsies from 168 patients with estrogen receptor–positive metastatic breast cancer and resistance to hormone therapies. Of these patients, 12 were found to have HER2 mutations, and 8 of these mutations had previously been described as activating. Based on available pretreatment primary biopsies, four of five patients with activating mutations had no evidence of preexisting HER2 mutations, suggesting they were acquired as a result of hormone therapy.
In addition, treatment resistance mediated by these HER2 mutations was overcome by combining the estrogen receptor–directed therapy with the HER2 kinase inhibitor neratinib. Dr. Wagle and colleagues indicate this novel combination therapy may prove to be an effective treatment strategy in these patients.
