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Correlation Between Quantitative HER-2 Protein Expression and Risk for Brain Metastases in HER-2+ Advanced Breast Cancer Patients Receiving Trastuzumab-Containing Therapy.

The oncologist 2012 Jan 10; 17(1):26-35

Link to PubMed abstract

Duchnowska R, Biernat W, Szostakiewicz B, Sperinde J, Piette F, Haddad M, Paquet A, Lie Y, Czartoryska-Arlukowicz B, Wysocki P, Jankowski T, Radecka B, Foszczynska-Kloda M, Litwiniuk M, Sylwia D, Weidler J, Huang W, Buyse M, Bates M, Jassem J

Warsaw, Poland;

AbstractBackground. Patients with human epidermal growth factor receptor (HER)-2(+) breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2(+) advanced breast cancer patients treated with trastuzumab.Methods. The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2(+) metastatic breast cancer. HER-2/neu gene copy number was quantified as the HER-2/centromeric probe for chromosome 17 (CEP17) ratio by central laboratory fluorescence in situ hybridization (FISH). HER-2 protein was quantified as total HER-2 protein expression (H2T) by the HERmark assay (Monogram Biosciences, Inc., South San Francisco, CA) in formalin-fixed, paraffin-embedded tumor samples. HER-2 variables were correlated with clinical features and TTBM was measured from the initiation of trastuzumab-containing therapy.Results. A higher H2T level (continuous variable) was correlated with shorter TTBM, whereas HER-2 amplification by FISH and a continuous HER-2/CEP17 ratio were not predictive (p = .013, .28, and .25, respectively). In the subset of patients that was centrally determined by FISH to be HER-2(+), an above-the-median H2T level was significantly associated with a shorter TTBM (hazard ratio, [HR], 2.4; p = .005), whereas this was not true for the median HER-2/CEP17 ratio by FISH (p = .4). Correlation between a continuous H2T level and TTBM was confirmed on multivariate analysis (HR, 3.3; p = .024).Conclusions. These data reveal a strong relationship between the quantitative HER-2 protein expression level and the risk for brain relapse in HER-2(+) advanced breast cancer patients. Consequently, quantitative assessment of HER-2 protein expression may inform and facilitate refinements in therapeutic treatment strategies for selected subpopulations of patients in this group.

Keywords: HER-2 Brain Metastases Trastuzumab Breast Cancer