Current and Future Status of Herceptin with Prof Debu Tripathy.

Professor Debu Tripathy of the University of Texas discussed new treatment options for breast cancer, in particular the current and future status of Herceptin.

Research interest: Growth factor receptor transduction.

Professor Tripathy discussed the history of HER2-neu (Human Epithelial Receptor) that targets the HER oncoprotein, which occurs in 25-30% of breast cancer. The professor noted that the tumours that express this protein perform much worse. Generally, overall survival (OS) is about 3 years, verses 6-7 years if it is not expressed.

In the Herceptin trial, if no prior anthracycline, patients were given AC plus Herceptin verses AC, if prior tax or tax plus Herceptin.

HER2-neu is probably an embryonic morphogen (similar to other adult oncogenes) that when targeted is responsible for normal cardiac development. It seems to be important for regeneration and restoration of function in cardiac remodelling. Hence, one potential side effect is the cardiomyopathy. Generally low incidence responds to conventional management and can be predicted on basis of previous medical history e.g. heavy pre-treatment with anthracyclines, previous cardiac disease.

Good news is that although HER2-neu expression equals worse disease, the addition of Herceptin to treatment equals a good response rate.

Herceptin works with a variety of other treatment including weekly paclitaxel 90mg/m2 plus Herceptin 4mg/kg (or 2mg/kg).

In HER2 positive patients, response rate (RR) was 69-81% with the most problematic toxicity being congestive heart failure (CHF) approximately 2%. Note: this responded well to standard treatment for heart failure and would often be predicted.

Ongoing laboratory investigations suggested significant synergy with Cisplatin, Gemcitabine, Vinorelbine, Docetaxel, and Carboplatin, e.g. Herceptin plus Vinorelbine 25mg/m2 when used first line has response rate of 85% and 80% overall.

Good results are also apparent with Gemcitabine plus Herceptin.

There are a number of ongoing trials for women who progress on AC or taxane plus Herceptin, looking at change to Vinorelbine and Herceptin.

Professor Tripathy stressed the importance of up-front testing of HER2-neu status.