Robert West

Publication Details

  • New cutpoints to identify increased HER2 copy number: analysis of a large, population-based cohort with long-term follow-up BREAST CANCER RESEARCH AND TREATMENT Jensen, K. C., Turbin, D. A., Leung, S., Miller, M. A., Johnson, K., Norris, B., Hastie, T., McKinney, S., Nielsen, T. O., Huntsman, D. G., Gilks, C. B., West, R. B. 2008; 112 (3): 453-459

    Abstract:

    HER2 gene amplification and/or protein overexpression in breast cancer is associated with a poor prognosis and predicts response to anti-HER2 therapy. We examine the natural history of breast cancers in relationship to increased HER2 copy numbers in a large population-based study.HER2 status was measured by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in approximately 1,400 breast cancer cases with greater than 15 years of follow-up. Protein expression was evaluated with two different commercially-available antibodies.We looked for subgroups of breast cancer with different clinical outcomes, based on HER2 FISH amplification ratio. The current HER2 ratio cut point for classifying HER2 positive and negative cases is 2.2. However, we found an increased risk of disease-specific death associated with FISH ratios of >1.5. An 'intermediate' group of cases with HER2 ratios between 1.5 and 2.2 was found to have a significantly better outcome than the conventional 'amplified' group (HER2 ratio >2.2) but a significantly worse outcome than groups with FISH ratios less than 1.5.Breast cancers with increased HER2 copy numbers (low level HER2 amplification), below the currently accepted positive threshold ratio of 2.2, showed a distinct, intermediate outcome when compared to HER2 unamplified tumors and tumors with HER2 ratios greater than 2.2. These findings suggest that a new cut point to determine HER2 positivity, at a ratio of 1.5 (well below the current recommended cut point of 2.2), should be evaluated.

    View details for DOI 10.1007/s10549-007-9887-y

    View details for Web of Science ID 000261951000007

    View details for PubMedID 18193353

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