Trastuzumab: not just for HER2-positive breast cancer anymore?

The monoclonal antibody trastuzumab (Herceptin) may be effective against HER2-negative breast cancers in addition to HER2-positive disease, based on recent research findings.

Current treatment guidelines for breast cancer limit the use of agents that block human epidermal growth factor receptor 2 (HER2) to tumors with HER2 gene amplification (HER2-positive disease). However, recent research has suggested that a wider group of patients might benefit from this therapy, wrote investigator Max S. Wicha, MD, director of the University of Michigan (UM) Comprehensive Cancer Center in Ann Arbor, Michigan, and colleagues, in Cancer Research (2013;73[5]:1635-1646).

As recounted in a UM Health System statement accompanying the release of the study, new analyses of old data had revealed that women whose tumors were incorrectly categorized as HER2-positive benefited from adjuvant trastuzumab therapy. Wicha's group explored the reasons for this development, and discovered that HER2 is selectively expressed in the cancer stem cells of many HER2-negative breast tumors. However, because cancer stem cells represent only 1% to 5% of all cells in a tumor, they don't express enough HER2 to meet the threshold for HER2-positive cancer.

The HER2-expressing cancer stem cells are resistant to chemotherapy and radiation treatments, but are effectively targeted by trastuzumab.

“We now provide a molecular explanation for the surprising finding that adjuvant Herceptin benefited some women with HER2-negative breast cancer,” affirmed Wicha in the statement.

Wicha's team also found that for tumors classified as HER2-negative, HER2 levels were higher in bone metastases than in the primary breast tumor. (Bone is the most frequent site to which breast cancer metastasizes.) When the investigators administered trastuzumab to mice with these bone lesions very early in the metastatic process, the drug almost completely blocked tumor growth. After the bone tumors were more established, trastuzumab had little effect.

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