HER2 Support Group Forums - View Single Post - putting risk of brain mets as first evidence of recurrence in perspective

Becky · 05-27-2006, 12:41 PM

I will let you know my theory on why folks treated with chemo and herceptin may experience more CNS mets that those who do not. Again - my thoughts only (based on cell biology mechanisms that are known).

1. when there is a primary tumor present, that primary tumor does send out anti-VEGF factors into the body. These factors prevent any micro mets that may be present not to be able to grow at the rate of the the primary tumor. This is a smart self preservation technique. The primary tumor says "I want all the nutrients etc. I am king here!!!" This is one reason why the oncs want you to start chemo asap after surgery and not wait too long (usually they want you to start within 3-4 wks of surgery) because, if micro mets are out there, they do not want them to take hold and be able to grow blood vessels (since the "king" is now gone). That said....

2. Let's say you did have a rash of cancer cells leave your tumor and lodge in various (and lets say common) places in your body - lungs, liver, bones and brain. You get your tumor removed and have chemo and herceptin. Neither crosses the blood brain barrier. Therefore, lets say this tx is successful and kills all the micromets.... except for the one(s) in your brain since the drugs could not reach it.

I think this might be the reason that if you do have systemic mets, CNS mets happen much much later in the process. Your "liver" mets curtail the growth of the brain mets (at least until a chemo/herceptin regime starts to knock out the liver mets and thus, the anti VEGF substances produced by the mets (which are secondary to the primary breast tumor but since that was knocked out (with surgery) the mets become the "new king".). (I sure hope I am making myself clear here).

So... why less CNS mets if only a hormonal is employed? It is well know that tamoxifen crosses the blood brain barrier so that is easily one answer.

Secondly, although it is not absolutely, entirely clear if aromatase inhibitors (AIs) cross the blood brain barrier, it is not important that they do in order for them to protect the brain. The reason for this is that they work to reduce and/or eliminate the production of estrogen. No estrogen, no binding to the estrogen receptor, no stimulation for a ER+ bc cell to grow and divide. So, all ER+ cells would be starving for estrogen and die (no matter where they are located and lodging).

Basically - chemo and herceptin protect the body but AIs and tamoxifen protect the brain (something we all hope Tykerb will do for those with Her2 and Her1 disease - especially if you are also NOT hormone positive as well).

I hope this is understandable because I do have a tendency to get ahead of myself.

Kindest regards

Becky

05-27-2006, 12:41 PM	#5
Becky Senior Member Join Date: Sep 2005 Location: Stockton, NJ Posts: 4,179	I will let you know my theory on why folks treated with chemo and herceptin may experience more CNS mets that those who do not. Again - my thoughts only (based on cell biology mechanisms that are known). 1. when there is a primary tumor present, that primary tumor does send out anti-VEGF factors into the body. These factors prevent any micro mets that may be present not to be able to grow at the rate of the the primary tumor. This is a smart self preservation technique. The primary tumor says "I want all the nutrients etc. I am king here!!!" This is one reason why the oncs want you to start chemo asap after surgery and not wait too long (usually they want you to start within 3-4 wks of surgery) because, if micro mets are out there, they do not want them to take hold and be able to grow blood vessels (since the "king" is now gone). That said.... 2. Let's say you did have a rash of cancer cells leave your tumor and lodge in various (and lets say common) places in your body - lungs, liver, bones and brain. You get your tumor removed and have chemo and herceptin. Neither crosses the blood brain barrier. Therefore, lets say this tx is successful and kills all the micromets.... except for the one(s) in your brain since the drugs could not reach it. I think this might be the reason that if you do have systemic mets, CNS mets happen much much later in the process. Your "liver" mets curtail the growth of the brain mets (at least until a chemo/herceptin regime starts to knock out the liver mets and thus, the anti VEGF substances produced by the mets (which are secondary to the primary breast tumor but since that was knocked out (with surgery) the mets become the "new king".). (I sure hope I am making myself clear here). So... why less CNS mets if only a hormonal is employed? It is well know that tamoxifen crosses the blood brain barrier so that is easily one answer. Secondly, although it is not absolutely, entirely clear if aromatase inhibitors (AIs) cross the blood brain barrier, it is not important that they do in order for them to protect the brain. The reason for this is that they work to reduce and/or eliminate the production of estrogen. No estrogen, no binding to the estrogen receptor, no stimulation for a ER+ bc cell to grow and divide. So, all ER+ cells would be starving for estrogen and die (no matter where they are located and lodging). Basically - chemo and herceptin protect the body but AIs and tamoxifen protect the brain (something we all hope Tykerb will do for those with Her2 and Her1 disease - especially if you are also NOT hormone positive as well). I hope this is understandable because I do have a tendency to get ahead of myself. Kindest regards Becky