[RobinP]

Hi Barbara,
Thanks for the compliment. I have tried to learn my best about molecular markers to determine Herceptin's response or resistance pre-clinically as this was a great area of interest to me to help me decide if I had a good reason to start late Herceptin. I must admit that I had the help of one of the speakers from the SABC to determine what markers I needed. He actually referred me to Dr. Bacus at TMD lab who defined that list even further and more specifically. I shall list each test for you that she recommended with a description as to why.

1. Her2 by FISH with overexpression ratio. A her2-CEP ratio of over 4 is truly OVEREXPRESSION and not just amplification. As you know, those with overexpression of her2 usually respond more to Herceptin.
2. TAB250 tests for the extracellular domain of her2 to see if you have an intact extracellular surface with cleavage where the Herceptin fits into like a lock and key. If you are missing this extracellular domain, Herceptin can not bind to its target site. I believe via of my research that about 25% of early stage her2+ breast cancer do not have this extracellular domain and have p95 or truncated form of her2 rather than the elonagated form, p185.
3. pTen-test for the presence of pTEN in your tumor. If you have pTEN, Herceptin well activate it. It is the activation of pTEN by Herceptin that causes decreased proliferation events almost immediately after receiving Herceptin, even before downreguation of her2 by herceptin. So if you have pTEN,you probably will be a good responder to Herceptin particularly early on via of Herceptin exposure.
4. Her1 test to see if you have EGFR or her1. If you do, you may not only respond to herceptin but you may be a good candidate for Lapatinib which acts on her1 and her2.
5. Her3. The overexpression of her3 may cause Herceptin resistence. However, if you only have moderate to low over- expression of her3, you will probably respond to Herceptin. Unfortunately, TMD did not give me a quantitative result on her3, I only know that I do have it but not aware of how much expression. Hopefully, I am a low expressor.
6. Her4 is not so much a marker to determine Herceptin response but having her4 is thought to be favorable prognostic characteristic.
7. IGF-suggest that the IGF-IR/HER-2 heterodimer contributes to trastuzumab resistance and justify the need for further studies examining this complex as a potential therapeutic target in breast cancers that have progressed while on trastuzumab.


One thing you must understand, is that her2 does not work in and by itself. Interestingly, this forum is focused on one Epidermal Growth Factor, Her2. However, Her2 can only carry out its cancerous proliferation events with other infidel family members, her1 or her3 as her2 has no known ligands to bind with. Her2 heterodimers with her1 or 3 to form strong cellular signaling to set off a cascade of proliferation events. I wonder if being her2 would be a problem if you did not have her1 and her3. Funny, how her1 and her3 just are not spoken here on these forums when they play such a pivotal role in her2's jaded character.

PS. PLEASE REMEMBER THAT ALL THESE MARKERS ARE PRE-CLINICAL INDICATORS OF HERCEPTIN RESPONSE AND THIS MAY NOT TURN OUT TO BE INDICATORS IN THE HUMAN RESPONSE OR IN VIVO EXPERIENCE. I BELIEVE AS TIME GOES ON, MORE CLINICAL TRAILS WILL FIND THAT THE PRE-CLINICAL EXPERIENCE WILL CORRELATE WITH THE IN VIVO EXPERIENCE. HOWEVER, UNTIL CLINCIAL TRAILS PROVE THESE MARKERS HAVE EFFICACY , THERE IS NO MEDICAL BASED EVIDENCE FOR THEM, AT LEAST AT THIS MOMENT IN TIME. NONETHELESS, IF YOU WANT TO DRAW YOUR OWN LOGICAL CONCLUSIONS AS I HAVE, YOU CAN.

I CAN'T WAIT TO SEE IF THEY LOOK BACK ON THE SPECIMENS FROM THE HERA TRAIL FOR THESE MARKERS TO FIND OUT WHICH INDIVIDUALS RESPONDED AND NOT TO HERCEPTIN.