[Gina]

Lani, LUCKY YOU..you caught me AT HOME after my Herceptin yesterday...a RARE day off...so I will have a moment to send you an infamous GINA LONG ANSWER...but first a couple of short ones...

One reason that Herceptin alone has worked for me so long is probably because I do not have a PTEN problem...and I extremely over-express her-2. I have no pathology report to prove the PTEN one way or the other, but if I am reading the one article right...the PTEN problem that sometimes may block the efficacy of Herceptin is also often associated with hereditary bc...as far as we have been able to determine, there is no hereditary BC in my family. Both Grandmothers lived into their 90's, very healthy their whole lives, very robust hard-working women. Neither my mother nor my two sisters have any BC or other cancers and are relatively healthy. My mother, as I mentioned on an earlier post, will be 70 this year and looks as though she will probably live at least as long as her mom,--91 or actually even make it to the magic 100. The men in my family, due to their dangerous occupations in the coal mines and railroad, died accidental or emphysema- related deaths, but no cancer as far as we know, but my one paternal grandfather who did make it into his eighties had a bone scan suspicious for bone mets at the very end, but died of black-lung related causes before we could confirm cancer dx one way or the other.

The second thing about my longevity with Herceptin that you have to remember is that even though I have used it off and on since 1999...you have to keep in mind...that I did not take very MUCH of it...

This was my choice and of course, at the time, counter to all HERCEPTIN wisdom...In 1999, I think I took 4mg one week, then 2mg, then 2mg, etc for about 5 or 6 weeks and stopped for nearly a year...then in 2000, mets in liver returned..so I took another 6 or so hits of herceptin...regressed the lesions back out and then went another year off Herceptin before mets struck a third time...This time, I decided to test 11 or 12 hits of herceptin to see if MORE herceptin would buy me more time to progression, but --as if on its own circadian rhythm..the mets would return on cue by the following year...this went on for 4 years until my really good onc left town and I was put with another onc who at a certain point...refused to let me go OFF the herceptin...but even then, I pushed the envelope...first moving immediately to the every 3 weeks and then, against ALL advice...pushing that envelope and moving the the 6mg /per kg for the every 3 weeks out to 6mg one time every 6 weeks...I did this for over a year and a half, until last September, as though on cue, my mets acted up and I went back to the more normal dosing of 6mg/kg...so you see...over all, I have taken SO LITTLE herceptin, that even though I am nearly 7 years with mets out, I may have actually taken LESS DOSINGS of herceptin than the average gal, say only 3 years out who has followed the standard dosing recommendations, either weekly or bi-weekly or every 3 weeks.

The third BIG difference in my case is that for the whole 7 years, by accident, I have been getting daily amounts of more oleic acid than the normal person because every day, since around July 1999, I have taken more or less the following supplements: 500mg of evening primrose oil (oleic acid and GLA rich (I take NO MORE THAN 500mg daily and only because I was and am still PRE-menopausal...this supplement may not be good for some one post menopausal and is also contraindicated for anyone who is taking cumidun for their port or to keep their blood from clotting as evening primrose is a powerful anticoagulant in its own right...but also remember...I DON't have a port and have not had one since it was removed after initial chemo in 1998); 25,000 I.U. Vitamin A with 800 to 1,000 I.U. Vitamin D in Solgar's fish oil tab with safflower...which accidentally turned out to be a specially genetically engineered safflower oil filler, rich in guess what??? OLEIC ACID!!!; a good basic multi-vitamin that contains another 5,000 I.U. of A as in palmatic acid (not just beta-carotene) and another 400 IU of D with equal calc to mag ratios...like 100mg to 100mg--as I do NOT especially believe that her-2 folks, for any reason, should ingest supplemental calcium..long story --my multi also contains zinc but no iron and traces of micro-nutrients like boron, copper (to balance zinc), etc. not too much B-6--as it blocks oleic acid..fyi); I take about one fourth of a kelp tab as more than that makes me eat like a fiend..smile.., and MOST importantly, I take a lot of magnesium..as I am always low...300mg of country life with silica and horsetail for breakfast with either another 400mg of PURE mag or PURE mag orotate, followed by another 700 to even 1,000mg later in the day...depending on how my platelets look...; then, around the year 2000, I added 500mg to 1,000mg of olive leaf capsules to my regimen, again, unaware of the connection the Dr. Mendenez was to make in early January 2005, and off and on, I would test so many things...like Hulda Clarks' formula...really appreciated the cloves...and tend to have taken them instead of the tumeric to kill "progeny" but at the moment, as so many have recommended tumeric on this site and especially when I saw one 'patient' with bc mets basically every where Except NOT in THE LIVER--which was a bit bizarre and later learned that she was a daily taker of tumeric...I decided for protecting the liver, it must be useful...will let you know how it goes with me...although I really think ground cloves hits this same mechanism. I also took Dr. Clark's green walnut tincture off and on which may be rich in oleic acid as walnuts certainly are, and tested her wormwood, but it gave me so much neurapathy and made me feel so tired like I was back on taxotere that I could not keep taking it, and WELL, THERE are so many alternatives I have tested--no joke, I have saved every bottle for posterity..smile as I was sure no one would believe me if I did live for a while, but the main ones that worked for my her-2, other than what I wrote above that have helped me have been echinacea, artichoke (for liver, I am allergic to ragweed and have difficulty taking milk thistle as they run in same family), zinc oxide on the feet (as in Desitin--to keep my lymphs up and grans down), and certain macrolide classes and quinolone classes of antibiotics--but only those that disrupt PLASMID protein synthesis and that are designed to hit aerobic (air BREATHING) gram NEGATIVE bacteria...antibiotics designed to take out anaerobic or gram positive bacteria, such as penicillins and the like, have zero effect, fyi as they work on a totally different destruction mechanism than those designed to disrupt plasmid protein synthesis.

However, HERE is MY question to the experts...some one REALLY needs to tell me how is it even possible for a monoclonal antibody to "become resistent"...all the herceptin does technically is connect up like a lock and key on her-2 receptors sitting on the cell surface. As long as you are over-expressing her-2 on some of your cells, the Herceptin, should, theoretically anyway, connect to those cells and those cells alone...like a key to a lock. It is your own body's immune system that later comes along BEHIND the herceptin and cleans up the herceptin-tagged/flagged cells as NOW the supposed CANCER cells have become apparent to our immune system and as soon as the hampster- tainted herceptin smell reaches the immune patrol...it knows that something that is NOT SELF is under foot and sends in reinforcements to take out the entire HERCEPTIN tagged cell. Unless something else is already sitting on the her-2 receptors and blocking the HERCEPTIN 's docking site--which may happen in some isolated cases, I really don't think that the herceptin has "stopped" working for most folks, meaning, that as long as they STILL have over-expressing her-2, the herceptin is still going to dock with the cells that are exhibiting the over-expression, provided nothing is blocking the docking site. That your cancer may be progressing is still quite possible, but the problem is NOT WITH THE HERCEPTIN...oh, brother..I AM GOING TO GET A LOT OF HATE mail for what I am about to say next, but as this post is so long...most folks won't read this far down..hee hee... so I will just say it. In practical experience...I have long -observed that it is the patient and their immune system which gives out LONG before the HERCEPTIN stops doing exactly what it was designed to do, but I see it so DIFFERENTLY from most folks.... Herceptin alone does not KILL cancer cells...although the final scientific word is still out...in my opinion, all the herceptin does is dock with and tag the cells over-expressing her-2 period dot. It is the PERSON's own immune system that has to come in BEHIND the herceptin and start using phagocytosis to eat up and clean up the lesion /tumor debris. In my opinion, we have not yet even begun to use herceptin properly...instead of being used like a class A chemo drug...it should be used more the way insulin is for diabetics...based on YOUR OWN TUMOR BURDEN as defined by how saturated YOU PERSONALLY ARE with serum her-2 tumor markers...because if you are pouring her-2 over-expressed protein into your bloodstream as I AM...you need to take ENOUGH herceptin to GET IN FRONT OF OR AHEAD of the deluge and then, you can bring it back under control and return to more maintainance dosing.

So, often, it is NOT that the herceptin has stopped working..it is just that you have MORE cells over-expressing the her-2 than the standard 2mg can hit--as 2mg is a limited substance that can only hit a finite number of her-2 over-expressing cells...LET ME EXPLAIN by using a model..what we sometimes call a "cartoon" in grad school....THIS IS VERY OVER-simplified but just to give you a mental SNAPSHOT of my idea--not proven..fyi:

Suppose that 2mg of herceptin administered every week is enough saturation to take out a finite number of up to 2,000 cells in your body over-expressing her-2. You take the herceptin, your immune system is plenty strong at first to RECOGNIZE that suddenly you have 2,000 hampsterish (smile) smelling cells in you, mount a response, administer phagocytosis and clean up the debris and wash it all out via your circulatory, digestive and lymph systems... OK...if you are on every 2- week dosing, your body must mount this attack EACH week...which means you must eat well and rest well and supplement well so that YOUR nutrient stores necessary to mount the attack are at the ready...we are all only human...it is very difficult to take the herceptin week after week after week after week...So, over time...what happens is the original 2,000 cells tagged in our cartoon by the herceptin...don't get completely cleaned up...remember, the herceptin is JUST docking with the her-2 receptors..it is NOT killing the cancer or causing the cell to commit apoptosis..., so what happens...some of the cells not taken out by your immune system start to multiply...from my tests on myself...my her-2 rate tends to double over time...faster if my body is in a stressed or weakened conditon slower, if I am fairly healthy...now suppose that instead of 2,000 cells over -expressing her-2, suppose you now have 4,000...remember that in the logic for this cartoon we stated that 2mg of herceptin has a finite number of cells that it can tag and for our purposes we set that number equal to 2,000. OK...so you go in, you take 2mg of herceptin..it tags 2,000 her-2 over-expressing cells, your weakened immune system takes out about 1500 of the 2,000 tagged ones...oh joy, guess what 4,000 minus 1500, leaves you with 2, 500 her-2 over expressing cells that may double before your next 2mg dose of herceptin..so guess what...this week you go to take your normal 2mg dose and you have 5,000 cells over -expressing her-2 and the 2mg dose tags 2,000, you have 3,000 left that may double to 6,000 before your next dose, and...WELL, you see it doesn't take much to progress using this model and the herceptin HAS NOT STOPPED DOING WHAT IT WAS DESIGNED TO DO--tag a finite number of cells over-expressing her-2--...sorry I am always so OUTSIDE the box, but this is just the way I see it.

Usually it is very easy to see in your own bloodwork that you are not getting enough herceptin to take out all your her-2 over -expressing cells...as the more cells you have over-expressing the her-2, the MORE her-2 protein will be dumped into your bloodstream..this is why it is beyond me why no one really pays that much attention to the serum her-2 numbers...these are not MYTHOLOGICAL entities playing peek-a-boo in our bloodsteams..it is my understanding that the only way this protein can increase in your blood is because you have CELLS inside you that are pumping it out....am I missing something here??? smile...

Also, as a footnote, MY CASE IS NOT STANDARD and it is important to remember, that every time I progressed, as I had BEEN off the herceptin for an extended time, and I was made to take both a prophylactic quinolone type antibiotic and a new RE-loading dose each time I got back on it and my numbers would DROP straight down by half and then, by the next week, the overall tumor burden would be manageable enough (as my original onc made a deal with me that if my numbers got to a certain number, we would return to treatment or else he would not let me go off the herceptin in the first place) that the 2mg dose in the early days, would be sufficient...however, we must also keep in mind that I may have been helping the herceptin do its job more efficiently and reducing the amount of herceptin I needed by taking the oleic acid rich supplements, keeping my immune system strong by refusing drugs like chemo, ativan, and benedryl, and by walking a LOT, and eating right and getting adequate rest. Plus, as a single mom with a tremendous zest for life, I was VERY motivated to live...sometimes, no matter how sick you are, that hard core motivation to survive is the single most important factor in doing just that..surviving.

It was also interesting to note that my cancer would progress more quickly every time I over-extended myself with my work or research or social activities...it was very important to maintain adequate rest and exercise at all times...that is why I had to learn over years of trial and error to rigidly adhere to my base regimen, even though I am somewhat of a free spirit and am not by nature, very disciplined...but having her-2 GAVE me no choice.

BOTTOM LINE: Before I would just randomly assume or "GUESS" that the herceptin wasn't working, I would do TWO THINGS: First, I would have my serum her-2 tumor marker levels checked several times to see where they were and if they were higher than 10, I would assume that I had cells in my body that were over-expressing the her-2 protein and dumping it into my blood at levels high enough for me to measure which would be a STRONG indication that I had cells over expressing her-2 in me. Once I empirically established active her-2 cells inside me, and was sure that my health and immune system were generally good and if my muga permitted it, I would ask for a higher reloading dose of herceptin, and hit it while continuing to take the markers..and follow through with as many consecutive dosings of herceptin as necessary to bring the serum her-2 numbers down into the single digits--and if the markers were way high...I would return to weekly or bi-weekly not every three weeks, until I could get ahead of the NUMERIC tumor progression, then attempt to return to herceptin maintenance--which can be more spaced out...once the markers consistently were under 10...BASIC CONCEPT: before trying anything else and certainly before ADDING an immune depleting chemo..I WOULD INSIST on being treated with more herceptin more frequently to see if you could drop the tumor burden and return to NED. IF that did not work, and if your GRANS were very high, over 80, I would consider adding micro taxol to knock way down the grans (neutrophils which may be propagating the her-2 mediated disease--I also would not under any circumstance take neulastin or any other drug designed to INCREASE neutrophils..fy), but I would do a lot of zinc and good nutrition and supplementation to keep the rest of the body intact and supply the immune system with every nutrient it needed to launch a full- scale attack on lots of her-2 tagged cells as in my model...it stands to reason that if 2mg of herceptin can hypothetically tag a finite number of say 2,000 over -expressing her-2 cells, then 4mg could hypothetically tag MORE, say double = 4,000 her-2 over-expressing cells, and 6mg could tag 6,000, and 8mg could tag 8,000, etc--for example, the real numbers are probably much MUCH HIGHER.

In fact, I have always been amazed that they give you a LOWER dose of herceptin after the first loading dose rather than the other way around...as it seems counter intuitive for a disease we all know tends to progress. For instance, I think it would be interesting to see a trial of 2mg the first week, followed by 4mg the second week, followed by 6mg the third week...of course, the worry is that this would be too hard on the heart--but if it could be proven that say the 2mg per week dosing of herceptin actually does just hit a finite number of cells, why not just give some of us with really bad mets a heavy 12mg from the start??? and see how long it is from mega hit to progression? I personally, would LOVE to volunteer for this, but alas, I am a poor test subject as I don't take direction very well...but I think herceptin has been proven safe for up to 14mg, but I am not sure. If my model of limited herceptin dosing hitting a finite number of cells is right, why are we wasting time and MONEY with all this 2mg stuff...when many of us are exhibiting serum her-2 levels over 500, even over 1,000. Anyway, it does not make good scientific sense to me, but from a business perspective of course, it is only logical...smile.

Anyway, the zinc will also especially boost the lymphs which have an inverse relationship to the grans...you want your lymphs high, and your grans LOW. This will also give you good energy flow. And anyhow, there may be a much SIMPLER solution to the whole problem than screwing around with the Herceptin dosing as the herceptin is merely hitting the her-2 which is already way DOWN stream from the source of the problem, but that is a story for another day off...smile.

In the final analysis, I am only a patient...what could I POSSIBLY KNOW???????.........................smile,
Gina