Background: The status of HER2 amplification in breast cancer is an important prognostic and predictive indicator. Only those tumors exhibiting HER2 overamplification are candidates for HER2 targeted therapy. It remains controversial how accurately HER2 status of primary tumors reflects HER2 status in distant metastases. Discordance between primary and metastatic tumors can impact significantly on patient management and suitability for HER2 targeted therapies in the setting of recurrent distant disease.

Methods: A literature search of the PubMed database was performed to identify all primary studies comparing HER2 status in matched primary and distant metastatic tumors between January 2005 and February 2011. Review and data extraction was performed by two independent reviewers. Eligible studies evaluated HER2 status by current ASCO guidelines. Studies comparing paired primary and axillary lymph nodes or synchronous primaries and metastases were excluded. Weighted pooled estimates were calculated.

Results: The original search strategy retrieved 1703 studies for which there were 62 eligible studies for full evaluation. Metastatic sites included bone, brain, lung and liver. Traztuzumab was received in three studies. Weighted summary estimate for negative to positive discordance was 23% (95% CI, 16.0-28%). Positive to negative discordance had a weighted summary estimate of 4% (95% CI, 0.0-6%).

Discussion: Meta analysis of studies adhering to ASCO guidelines for HER2 status determination revealed a significant rate of change to HER2 positive metastatic disease in HER2 unamplified primary breast cancers. This data suggests that nearly one quarter of patients may be denied the benefit of HER2 targeted therapy if HER2 primary status alone is used a the sole measure in determining therapeutic options upon distant recurrence.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-05.