Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.</p> <p>Methods</p> <p>HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence <it>in situ </it>hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.</p> <p>Results</p> <p>Median time to progression and overall survival were 9 (range 2 - 54) and 20 (range 3 - 101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (<it>p </it>= 0.05) and higher stage (<it>p </it>= 0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53 ± 10.21 vs 2.50 ± 4.12, <it>p </it>= 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (<it>p </it>= 0.046). p53 expression was only associated with higher stage disease (<it>p </it>= 0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.</p> <p>Conclusion</p> <p>Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.</p