In order to accurately interpret HER2 test results, Joyce A. O’Shaughnessy, MD, recommends following the ASCO/CAP guidelines, which were updated in October 2013. The revisions now indicate that tumors are HER2-positive by IHC if protein expression is greater than 3 in more than 10% of cells. Also, by ISH testing, tumors are HER2-positive if the HER2/CEP17 ratio is greater than 2 or the HER2 gene copy number is over 6. These revisions make the guidelines more helpful in the clinic and are based on evidence from clinical studies, notes O’Shaughnessy.

ISH and IHC assays should be used preferentially for detecting HER2 status, as opposed to RT-PCR or microarrays, Hope S. Rugo, MD, believes. In some situations, expression based tests may incorrectly identify a patients as HER2-positive or negative, resulting in patients not receiving the most effective therapy. Moreover, the utilization of HER2-targeted therapies results in an improvement in survival for patients with breast cancer, which makes detecting HER2 positivity even more important, notes Kimberly L. Blackwell, MD.

In addition to optimizing testing strategies for HER2-positive breast cancer, studies are examining the optimization of dosing. One such study, explains Denise A. Yardley, MD, is exploring a weekly schedule of T-DM1 plus pertuzumab. This study will add to the clinical trial data already anticipated in the first-line setting from the MARIANNE study, which is exploring T-DM1 plus or minus pertuzumab compared to trastuzumab plus a taxane for untreated patients with HER2-positive metastatic breast cancer.