New research from the University of Michigan Comprehensive Oncology Center has found that the HER2 protein still plays a role even in breast cancers traditionally classified as HER2 negative, and if so, then the HER2-targeted drug Herceptin may play an additional role in breast cancer treatment and prevention of spread. About 20 percent of breast cancers are HER2-positive. Since its introduction, Herceptin has provided a significant survival benefit for HER2-positive breast cancer patients, especially when used as post-operative adjuvant therapy. This finding could potentially impact the treatment of the other 65% of women with breast cancer. A recent study re-analyzed data from previous studies and found that some tumors were incorrectly classified as HER2-positive, resulting in these women receiving adjuvant Herceptin therapy. The results showed that these patients had the same benefit as those who were HER2-positive. “We have now found a molecular explanation for this surprising finding that adjuvant therapy with Herceptin benefits HER2-negative patients. If these results can be confirmed in clinical trials, it will change the landscape of breast cancer treatment,” said article author Max S. Wicha, MD, PhD, distinguished professor of oncology and director of the Center for Integrative Oncology Research at U-M. Until now, Herceptin has not been considered for treatment of HER2-negative breast cancer patients. The reason for this may be that many HER2-negative breast cancers have tumor stem cells that selectively express HER2. the number of stem cells in the tumor is small, and HER2 expression is not sufficient to reach the threshold of positivity in HER2-positive breast cancers. The results were published online in the Journal of Oncology Research. Previous studies have shown that HER2 plays an important role in tumor stem cells, which, although small in number, are the engine of tumor growth and spread. It accounts for approximately one to five percent of all tumor cells. Stem cells are resistant to current chemotherapy and radiotherapy, but if they express HER2 protein, they can be targeted by Herceptin. In addition, the researchers in this study found that HER2 levels were higher in bone metastatic tumors of patients with HER2-negative cancers than in the primary tumor site. And the most common site of metastasis in breast cancer is bone metastasis. The investigators gave Herceptin to mice with bone metastases and found that the earlier the drug was given, the more effective it was, especially when the tumors were small or only minimally metastatic. In these cases, Herceptin almost completely blocked the growth of the tumors. When the tumors were already large when administered a little later, the efficacy was less pronounced. ”If Herceptin targets the bone micrometastatic environment, giving the drug before metastases develop could help reduce tumor recurrence,” said study author Hasan Korkaya, MD, assistant professor of internal medicine at the U-M School of Medicine. The implication of this research is that we need cancer therapies that not only kill a large number of tumor cells with chemotherapy, but also target a small number of tumor stem cells. This means that treatments that focus solely on shrinking tumor foci may not provide long-term benefits.