November 2, 2008

Capturing article info...

HER2 Breast Cancer Vaccine Shows Promise In Lab

September 25th, 2008 by allsoch

Researchers in the US are hoping that their new breast cancer vaccine will be effective in humans because it safely destroyed HER2-positive tumors, even those resistant to anti-HER2 drugs, when tested on mice.

The study was the work of scientists at the School of Medicine and Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, and is published in the September 15 issue of Cancer Research, a journal of the American Association for Cancer Research.

HER2 (Human Epidermal growth factor Receptor 2) is a receptor that sits on the surface of cells in breast tissue. Their normal job is to promote cell growth, but when there are too many of them, the growth becomes uncontrolled and forms very aggressive tumors. Up to 30 per cent of breast cancers are of this HER2-positive type.

Conventional treatments rely on drugs like Herceptin (trastuzumab) and Tykerb (lapatinib) that bind to and disable the HER2 receptors, but a significant number of patients eventually become resistant to them.

The researchers hope this study will lead to a vaccine for women with HER2-positive breast cancer that has become resistant to treatment, or perhaps stop it recurring. They said it also shows promise as a cancer-prevention vaccine in women who are cancer free.

Principal investigator Dr Wei-Zen Wei, professor of immunology and microbiology at the Karmanos Cancer Institute, said the vaccine activated the patient's own immune system to destroy the cancer.

"The immune response against HER2-positive receptors we saw in this study is powerful, and works even in tumors that are resistant to current therapies," said Wei.

"The vaccine could potentially eliminate the need to even use these therapies," she added.

When there is a low level of HER2, such as that expressed when they are on the surface of normal cells, the immune system ignores them. But if there is a sudden and enormous change in HER2 receptors, the immune system responds as if to an attack and learns very quickly to destroy them.

This was the mechanism that Wei and colleagues decided to provoke, using "naked" DNA genes to produce the HER2 receptors, and a stimulant to boost the immune system response. They used a bacterial plasmid to encapsulate these two ingredients and then with the aid of electrical pulses they injected them into the leg muscles of mice.

The stimulant the researchers injected at the same time as the HER2 gene, was an agent that temporarily suppresses the regulatory T cells that stop the immune system from over-reacting, thus causing a much stronger reaction than normal and giving the immunisation process a head start.

The gene very quickly produced large numbers of HER2 receptors and the immune system responded with large numbers of antibodies and killer T cells. When they implanted HER2-positive breast tumors in the animals, the cancer was eradicated. As Wei explained:

"Both tumor cells that respond to current targeted therapies and those that are resistant to these treatments were eradicated."

"This may be an answer for women with these tumors who become resistant to the current therapies," she added.

This is the second HER2 DNA vaccine that Wei and her team have developed. The first was in 1999, when they published a study that led to the development of a vaccine that is currently in early phase clinical trials in the US and Europe on women with HER2-positive breast cancer.

The new version uses HER2 genes that have been altered so they can't become "oncogenic". The earlier version retained traces of the underlying receptor structure, and when this happens there is a slight risk this can trigger tumor formation later, because the "signalling" system of the receptor is still active and can communicate with the cell nucleus.

Wei said the first vaccine was safe, but it contained a bit more of the "native" HER2 receptor structure, whereas "With this vaccine, I am quite certain the receptor is functionally dead," she said.

October 16, 2008

I saw this post in the Her2 site and I don't want to forget about this combination of meds for Stage 4. Doesn't have anything to do with me, however I may need it down the road!

Ixabepilone & Tykerb

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Success with this combination after only 3 treatments. My wife, Kathleen, is 58 yrs old, original breast cancer 7 years ago, removed left breast, standard chemo & radiation. Followed for 6 yrs with Herceptin when treatment discontinued. 9 months later her cancer returned with 3 lymph nodes involved and a mass above her heart. Treated with Tykerb & Xeloda for 9 cycles with terrible side effects & progression of disease. PET scan disclosed 8 lymph nodes involved, growth of mass above heart, & small mass in plura space below left lung. Discontinued Xeloda and began infusions of Ixabepilone every 3 weeks and continued daily Tykerb. After 3 infusions cancer is undetectable on PET scan. Will continue infusions for at least 2 more cycles & thereafter the plan is to continue daily Tykerb and monitor cancer. Consider this treatment!

July 30

I visited Kevin Mortara, my oncologist, yesterday.  I had a bunch of stuff to discuss with him, and it's interesting, because that's what it really is with our appointments...interactive discussions.  In my opinion we have the perfect doctor/patient relationship: I stay current on the science behind my condition so that he and I can talk through things on the same level (well, maybe not the exact same level since I'm not a doctor!) and decide my course of treatment together. 

Obviously one of the things we talked about is my new case and its pathology.  I was troubled by the fact that they wouldn't test for Her2 this time.  Before I met with Kevin, I emailed Walt Carney, who heads up oncogene science at Siemens Healthcare Diagnostics in Cambridge MA (he is one of the guys I interviewed a couple years ago when I wrote the BC feature story for the Scene; we have stayed in touch because his research involves Her2 cancer).  I was looking for a second opinion about the pathology of this new case, and he checked with a pathology friend of his who heads up pathology at a large Boston hospital).  He concurred with the opinion that there isn't a need for Her2 testing in this situation because Herceptin is only given for invasive cancers.  In other words, since I would not change my course of treatment if the sample turned out to be Her2+, there is no need to test.  I asked that Kevin check to see how long BC tissue samples are retained because I want to make sure that for future reference that my samples are retained for the maximum possible time.  With all the advances in cancer treatment now and expected to occur in the future, I want to retain the ability to retest these samples if doing so would open up opportunities for alternative future treatments should my cancer recur.  The current cancer doesn't carry much risk of recurrence, but the case form a couple years ago still does.

The new was indeed staged at Stage 0 (zero).  Cases are staged between 0 and 4.  Stage 4 is when the tumor has spread to other body parts, such as lung, liver, brain, or bones.  So if you have to have cancer, stage 0 is the best way to go!  I will not need any further treatment for this new case.  Tamoxifen is only indicated when there is breast tissue left to save.  Many times it's women who undergo a lumpectomy who use Tamoxifen for usually five years post-treatment.  I think the stats are that if I took it, my chances of recurrence change by a really tiny number, and this case doesn't have high odds of recurrence anyway.  So I'm pretty happy that I don't need to pursue any follow up treatment.

We also discussed my ongoing Herceptin treatments.  Even if I hadn't developed this new case of cancer, I was contemplating discontinuing Herceptin.  Women with Her2+ breast cancer who have received ongoing Herceptin for metastasized cancer have sometimes gotten to the point where they stop responding to Herceptin.  In case I end up with mets in the future, I want to keep Herceptin in the "bag of tricks."  So last week was my final injection, hopefully forever!

With Herceptin out of the picture, the only thing I'm still doing is getting an annual brain MRI (I'm sure my employer, which is also my health plan, will be happy about the cost savings!).  I may also start getting the Bayer serum test (the one developed by Walt Carney's team).  I'm re-reading some of the journal articles about it and will talk to Kevin Mortara next week about starting it.  This test checks for Her2 markers and has been shown to be an effective way to monitor whether there is tumor growth somewhere in the body.  But if mets develop that are not Her2 I don't know that there is a test for that.  What's interesting is that a primary tumor that is Her2 positive (like mine from a couple years ago) still contains cancer cells of other types, so a predominantly Her2+ tumors can still result in future mets that are of a different type.  This happens when one or more of the minority non-Her2 cells are the ones to "escape."  Mortara's advice was that, aside from mets to the liver, the best way to monitor for tumor mets is to pay attention to your body.  Bone pain can indicate bone mets, and lung mets aren't that hard to discover because there are obvious symptoms.  The liver isn't so easy.  And I have the MRIs to keep an eye out for brain mets.

The final thing I asked Kevin Mortara about is the effect that diet and alcohol have on the odds of recurrence.  And his reply was the same as I thought.  Are there people out there who will tell you that you should eat no sugar and drink no alcohol, there is no data that is definitive.  Everything in moderation is the way to go.  So I went out and bought a four-pack of those double chocolate muffins from Copps and ate one when I got home.  I'll saved the alcohol for the next day :-)

I was so curious about whether this new case, if it hadn't been caught, would have developed to be a similar case to the one a couple years ago.  But I'll never know, and that's fine with me.  I'm really pleased that this new case turned out to be such an early stage!

Val

P.S. I probably won't write an update for awhile, because I don't anticipate any new news.  But that's a good thing!!!

July 17

Recovery has been fairly smooth sailing.  I have been back at work full time this week and I'm still feeling fine.  I haven't yet gone back to teaching my biking classes at the Neenah YMCA, but I expect I will be back doing that next week or for sure the following week.  The surgical site remains a little bit sore, but at this point it's really no more than a minor irritant.

I was supposed to have an appointment with my oncologist this afternoon, but when I got there they said that they thought that I had canceled it.  I called earlier in the week and told them that I was postponing my Herceptin injection but that I would still see the doc, but they must have gotten confused.  So now I need to wait a week or two.  And I still don't know the Her2 results, so hopefully I will be able to track that down soon.  When I met with the surgeon, she told me that the post-treatment drugs women take for ER/PR positive breast cancer only prevent breast cancer, and since I had my breast tissue removed, I have nothing to protect.  But now I'll have to wait until I get al the path results and I have a chance to talk to my oncologist before I decide if I want to do something different than I have already been doing.  So I'll have to tell you about that in a later post.

Thanks so much for all your cards, well wishes and surprises--all of it really makes me smile :-)

I went to work for awhile today and am feeling pretty much back to normal; still a little bit sore, but nothing out of the ordinary.  So far I've only gotten part of the pathology results on my cells, and how weird is this...the path is different this time than last time.  Last time the cells were Her2 positive and ER & PR negative (ER and PR stands for estrogen and progesterone receptors, which are basically markers that describe cancer cells).  This time the cells are ER positive and PR negative; the Her2 results aren't back yet. 

This means I will likely be taking Tamoxifen or Femara, which are commonly taken for 5 years post-breast cancer treatment.  They are only indicated for patients with ER/PR positive cells, so I need to read up on them because they weren't applicable for me last time.  And having positive receptors is usually considered a good thing, because then these types of drugs can be used; there really aren't any post-treatment drugs when the cells are ER/PR negative.  That's why I've been doing the Herceptin quarterly--no other real choices.

But without doing more research and/or talking to my oncologist, I'm not sure what the ramifications are of one positive receptor and the other negative, and I'm not sure how things change, if at all, if the Her2 receptor is positive.  And I still want to do something preventative with regard to the cells from last time.  So I have some thinking to do :-)

July 5, 2008

All the bandages are off, so I took a full shower today.  Thankfully I don't have to rely any longer on a 13-year old girl to wash my hair in the kitchen sink.  Yesterday I finally just asked her for the sprayer and I finished the job myself.  I told Jane that I hoped that I will someday never need her to be my primary care giver because I would most certainly be a neglected patient!  I think it's just that 13-year olds have better things to do, even if there's nothing else going on.  I love my showers and can't stand it when someone tells me I can't take one, but I must admit it's interesting how much of a shower one can take without actually taking a shower.  It's not even that hard to shave.  Desperation usually results in finding a way to do almost anything!

I left a band-aid on the spot where the drain came out.  It kinda freaks me out that I had this long tube inserted way inside by body, and then they yank it and just cover it up with gauze and tape.  But it looks as if it healed up OK, so I put on the band-aid just to make sure it doesn't get rubbed and start bleeding or something.

Yesterday was also my first party since surgery.  Some friends of ours own their grandmother's former home on the Neenah harbor and they are remodeling it -- right now it's completely gutted.  They had a cookout/party there for the 4th, probably because they have a perfect view for the fireworks.  We didn't stay for that part because we were going to have a houseful of kids over -- both Jane and Charlie were planning to have friends over after the fireworks and we had be there to do our parental due diligence.

Today I am planning to go shopping and then I'll lay around and read.  I read a book on Wednesday that was pretty good, but I can't remember the name of it -- it's already ben returned to the library (I'm really bad at remembering the names of books I read--probably because I read lots of them--once I was 70 pages into a book before I realized I had already read it years earlier).  It was a novel about the turmoil in Iran and involved a family who fled the country; the father was imprisoned during part of the book.  The book I'll read today is called House of Sand and Fog and it's also about a middle-eastern family but takes place in San Francisco after they flee their country.  I must have read reviews of these books somewhere and decided to reserve them, because they came up on my list at the same time.  I love the library reservation system..now you can even specify when you want the book (as opposed to reserving it and having it arrive right away--if you have a lot of books you want and they all come at once, then what?)

I paid a visit to the surgeon's office today because the post-op drain wasn't really collecting much.  I was worried that it was clogged, but I also thought that because it hadn't really drained that much since the surgery that I could maybe ask them to remove it today.  Peggy, the nurse who works with my surgeon, offered me the choice of having it pulled or waiting it out.  The worst that can happen in a situation like that is that some fluid would build up internally, but eventually the body takes care of it.  So, surprise surprise, I opted to have it pulled.  Things sure are a lot easier without that to worry about!

I'm feeling pretty good today, not much nausea any longer.  My only mistake is sitting here watching Saw III and Saw IV...not the best movies to watch after you've recently been cut open.  But the movies are here and I want to see them before they have to go back to the video store, so here I sit watching them :-)