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Short HER2 Receptor Affects Tumor Response to Therapy

Tumors with shortened version of HER2 are resistant to trastuzumab and sensitive to lapatinib

WEDNESDAY, April 18 (HealthDay News) -- Breast cancer patients who have tumors that produce a shortened version of the HER2 receptor are resistant to trastuzumab, which cannot bind to the short receptor, but may be sensitive to lapatinib, according to a study in the April 18 issue of the Journal of the National Cancer Institute.

Jose Baselga, M.D., Ph.D., from Vall d'Hebron University Hospital and Research Institute in Barcelona, Spain, and colleagues compared the sensitivity of breast cancer cells producing the shortened HER2 (p95HER2) or full-length HER2 to trastuzumab and lapatinib.

The researchers found that lapatinib inhibited the growth of p95HER2-expressing cells, as well as similar tumors in mice, while trastuzumab had no effect. Of nine metastatic breast cancer patients producing p95HER2, only 11.1 percent responded to trastuzumab (one patient, a partial response), while 51.4 percent of 37 patients producing full-length HER2 responded to trastuzumab.

"Our findings support that further characterization of HER2-expressing breast tumors, based on the presence or absence of p95HER2, may assist in the selection of the appropriate anti-HER2 therapy," Baselga and colleagues concluded.

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