Current method of assessing patients’ entry for treatment of signal transduction inhibitor is limited. About 30% of breast cancer patients overexpress the ErbB2 (HER2/neu) receptor but of those patients, only 35% with 3+ over-expression respond to trastuzumab. This indicates the limited capacity of the immunohistochmistry or FISH method alone in predicting treatment success of these patients as the overexpression of the ErbB2 may not correlate with the functional status of these receptors. A methodology to improve assessment of not just concentration of signal transduction target but their status, is urgently needed. This is further emphasized by the recent adjuvant trastuzumab trials reported from ASCO 2005 and NEJM 2005 (HERA,NSABP-B31 and NCCTG-N9831 trials) which showed an improvement in disease-free survival by trastuzumab in the adjuvant setting. The findings will encourage clinicians to use molecular therapy early on in the disease process, even before signs of disease recurrence, and hence the greater need of identifying patients who will benefit from this type of molecular therapy. We have developed a new innovative analytical approach to measure functional status of these signal transductions using FRET efficiency by High Throughput Fluorescence Lifetime Microscopy (FLIM) in the tumour arrays. We have previously validated this FRET method to assess ErbB1 functional status in cells (A431 cells & MCF cells) and head and neck tumour arrays. We have now applied the method to assess ErbB2 functional status in breast tumour arrays and will correlate the results with clinical and survival data. These results will be compared with that of ErbB1 activation status in breast tumour arrays as there is evidence to suggest that synchronous activation of both receptors is synergistic. The FRET efficiency by FLIM has great potential to be a prognostic marker and to be a predictive marker for treatment success of trastuzumab and other molecular therapy, complementary to the immunohistochemistry.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]