Waiting on Trial, got Brain Mets...

[julierene]

I was waiting on this perfect trial for my genetic p53 issue, but they required 4 weeks of being off therapy with growing disease. They had to have something to "measure". During my talks with the doctor who lead the trial, I asked "What about brain mets?". His initial reaction was that it 'should' work on them too. Well during my pre-screening I asked the nurse if she could check out my head, because I had felt a little like a sinus headache had been hanging on too long.

I was supposed to start the trail today, and I found out on Thursday that the brain CT had spots of salt and pepper everywhere and that I have one little 12 mm tumor too. They are putting my trial on hold until I get WBR (which is starting today). Apparently, the low blood pressure and high-grade fevers made them very nervous about putting me in the trial right now. But the BAD part is, if I don't get the brain mets under control, I fear where this might be headed. I have 3 children 10,9, and 5. I was divorced by a cheating husband 2 years ago, but leaning on my parents and boyfriend a lot right now.

I am so scared, even though the radiologist said he felt 80% responded to the 3 week / 14 day WBR cycle. And this is really stupid too, but I have lost my hair 3 times since I was 28. I am 34 years old, and SICK of loosing my hair. Doesn't the hair get tired of coming back after loosing it so many times? How vain is that? I just want to keep what I have, and not feel so battered by cancer anymore. Loosing my hair felt worse to me than my breasts!

I know you women understand. So I am hoping I can get some kind of reassurance that my hair will grow back, that maybe this WBR therapy will work long enough to get me back in the p53 trial. It's my only chance at getting something that might work. I have a p53 mutation, and I have been watching the trials for about 6 years now. This one seemed like my shot, now was the day I was waiting for... and it just got snagged right out from under me.

I know that I might get another chance at it, but I am terrified that I trusted this trial doctor with my life, and I took the wrong gamble. If I just could have ignored the 'sinus' pressure and little hints of dizziness, I would be sitting in the trial right now. I am so upset with myself. I am so upset with the trial doctor saying that they thought it would penetrate the blood-brain barrier. If I had ever thought I might get 'put on hold', I never would have had it checked. How do I deal with this huge mistake? I feel like I just cost myself my life... and it's all my fault or something...

[Ellie F]

Hi
I just don't have the words to express how sorry I am that you are facing this difficulty after such a long struggle to get on a trial. I have read a lot about p53 but didn't know they could actually test to see if it was knocked out. I am aware that some people believe vaccines given to children in the late 50's and 60's has been linked to this problem.
Please try not to despair. From your post it sounds like the door to the trial will still be open when you have had the WBR so it is by no means the end of the road.
I have lost my hair twice in 12 months and fully understand your feelings about it. Some morning's I look in the mirror and don't recognise the person I used to think I was!
You will be in my thoughts
Love Ellie

[Lani]

something to think about--
Unfortunately it may require you having a biopsy of your brain met--I do not know if examining the biopsy of your primary tumor for the symporter will suffice. (It seems 80% of her2+ brain mets have the symporter from one of the articles below.)

If so, you might want think about sending some of the specimen for testing for Na/I symporter, a marker which theoretically makes treatment with radioactive iodine possible (simple treatment, small molecules so should cross the blood-brain barrier, already FDA approved for treatment of thyroid disorders). The other variable which decides whether one is a candidate for this treatment from what I understand is knowing how much radiation the brain has already had, so it sounds like it is something worth looking into BEFORE deciding for WBR.

Might help you "not burn any bridges" Again, the good news is that it is already FDA approved and that they are already authorized to treat patients it seems.

J Neurooncol. 2009 Jul 19. [Epub ahead of print]

Breast cancer brain metastases express the sodium iodide symporter.

Renier C, Vogel H, Offor O, Yao C, Wapnir I.
Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive H 3625, Stanford, 94305-5655, CA, USA.
Breast cancer brain metastases are on the rise and their treatment is hampered by the limited entry and efficacy of anticancer drugs in this sanctuary. The sodium iodidesymporter, NIS, actively transports iodide across the plasma membrane and is exploited clinically to deliver radioactive iodide into cells. As in thyroid cancers, NIS is expressed in many breast cancers including primary and metastatic tumors. In this study NIS expression was analyzed for the first time in 28 cases of breast cancer brain metastases using a polyclonal anti-NIS antibody directed against the terminal C-peptide of human NIS gene and immunohistochemical methods. Twenty-five tumors (84%) in this retrospective series were estrogen/progesterone receptor-negative and 15 (53.6%) were HER2+. Overall 21 (75%) cases and 80% of HER2 positive metastases were NIS positive. While the predominant pattern of NIS immunoreactivity is intracellular, plasma membrane immunopositivity was detected at least focally in 23.8% of NIS-positive samples. Altogether, these findings indicate that NIS expression is prevalent in breast cancer brain metastases and could have a therapeutic role via the delivery of radioactive iodide and selective ablation of tumor cells.
PMID: 19618116

^^^^^

Mol Imaging. 2006 Apr-Jun;5(2):76-84. Links
Bioluminescent Monitoring of NIS-mediated 131I Ablative Effects in MCF-7 Xenografts.

Ghosh M,
Gambhir SS,
De A,
Nowels K,
Goris M,
Wapnir I.
Stanford University School of Medicine.
AbstractOptical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with 131I is predicated on the expression of the Na+/I- symporter (NIS) in many tumors and uptake of I- in some. The pattern of 131I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of 131I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in 131I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in 131I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less 99mTcO4- than untreated tumors. NIS immunoreactivity was present in <50% of 131I-treated cells compared to 85-90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after 131I administration was observed in NIS-expressing breast cancer xenografts.
PMID: 16954021
^^^
I think Dr. Wapnir is the one running the pilot study/trial:
AUG. 26, 2009
.




Lasting impressions: Wapnir on the memory of a breast cancer patient
BY DIANE ROGERS


Every doctor carries at least one patient in his or her head—a memory of a difficult case, perhaps, or of a tragic outcome. And sometimes there’s a patient who simply touches the heart. This is one in an occasional series about the patients they carry.

Breast surgeon Irene Wapnir keeps a photo of Patty taped to her office door.

“People have asked me how long I’m going to leave it there, and I say, ‘I don’t know—until it falls off?’”

Wapnir takes a long, studied look at the young woman’s face and her timeless smile. “She’s one of those people who looked me squarely in the eye and said, ‘This, too, shall pass.’ Even though she must have understood ....”


Patty was one of Wapnir’s patients who didn’t make it. A couple of years after her breast cancer was successfully treated, Patty’s disease metastasized to her brain. “And the brain is a particularly hard place for us to treat,” Wapnir noted.

Metastatic breast cancer in the brain is relatively common today. “More patients present with metastasis to the brain as their only site of cancer, in part because chemotherapy has gotten better at eliminating metastasis elsewhere,” Wapnir explained. While she is encouraged by therapeutic advances in the field—surgery, radiation and biological therapies now prove successful in 30 percent of such patients—there is much room for improvement.

As a result of seeing Patty and other patients with the same condition, Wapnir began concentrating her research on finding alternative ways to treat breast cancer brain metastases. Stanford’s Cancer Center is offering many cutting-edge therapies for the disease, including one that Wapnir is developing that involves the use of radioactive iodide. Although novel for breast cancer, radioactive iodide has been used for decades to detect and treat thyroid cancer.

“Now it looks like this approach could be applied to brain metastases,” Wapnir said, though much more research needs to be done. She is doing a pilot study on this subject for women with advanced breast cancer, work that is supported by the Stanford Center for Clinical and Translational Education and Research.

When Wapnir looks at her photo of Patty, who died three years ago, she sometimes gets a little teary. “There are patients who’ve looked at me and said, ‘I’m going to get through this, I’m going to keep on going,’ and that hasn’t always been the case.”

Patty’s tenacity spurs her on in her efforts to treat women who develop brain metastases. “Patty helped me to focus on this problem,” she said.

[julierene]

I don't have time to research any of this....

[Lani]

are you sure? are there mets on your brainstem? did they put you on steroids?

It may be that just discussing it with the rad onc who is going to treat you might allow him/her to check with Dr. Wapnir re whether you are burning any bridges by going straight for WBR right away. If not, then great. If so, then he/she could give you an opinion on what your options might be after talking with Dr. Wapnir.

It sound as if you already have at least one circumstance for which (rightly or wrongly) you are blaming yourself and/or your doctors for not getting more information before proceeding/ proceeding differently. Perhaps one or two questions could clarify whether this is an instance where you have an alternative or not and whether or not steps can be taken to make it more certain you have more alternatives in the future.

.

[margiermc]

you are a beautiful girl, so sorry to hear this - letting dr. know about your aches is the right thing to do, i learned not to beat myself up, im 46, and did not have mam. in 3 years, told I have dense breast.
I felt guilty, let myself down, let my kids down, done this for to long -it doesn't help. My hair was down the middle of my back, it looked
like the late Farah Fawcett hair, i cried losing it at this age - it's not about the hair, I learned that - at your age i understand - my hair, was my signature look. But, it grew back in 3 month, thick, wavy, blonde - and i enjoy it short - i get alot of compliments. email Joe -
about brain met - we are all scared with you - i'm going to pray heavily for you - for a healing! I will demand it! you have too much to live for - take care margie see my pics at washington, with my short hair www.caringbridge.org/visit/margierose


8/08 - dcis/lump.
10/08-liver met (almost died of liver failure)
2/11/09 - last chemo TCH
Her every 3wk
vaccine 6 mon last in Nov. 09

[Ruth]

Oh Julierene ~
I am sending you lots of hugs and prayers. You will be here for your precious babies! Let the WBR zap it out and get on that trial. I'm not sure about the hair part...I think Chrisitine or Joe would know this? Could they not do Gamma knife? Please don't think you did the wrong thing by telling them about your sinus headache and slight dizziness. I would think it would be much worse to let the brain mets grow without treatment versus delaying the trial.

I know how you feel about losing your hair - it was harder for me than losing my breast too. The hair is something you see whereas you can hide the lost breast in clothes etc. Losing hair gives cancer a face. I feel deeply for you and hopefully it will grow back or not fall out at all. Christine is such an inspiration and look at what she has accomplished with brain mets...you can too! Don't give up hope, please. We are here for you!
Hugs ~ Ruth
I just read StephN thread...please read it and it will give you much hope.

[MJo]

Please come here to bitch and complain. I read your other post, and I know when we hit bottom it all feels so bad. " I made the wrong choice...I had a *()*_&*(&() husband... and now look where I am!!" Plus you have to be strong mommy to three little kids. I think there is lots of hope for you - whole brain rads, then into the trial. As for Lani's posts, you don't have to do any research. Just print them out and hand them to the doc.

I feel like you need a big teddy bear to hug -- maybe that's your boy friend. I am amazed at the s--t you've gone through so young. You deserve to scream and holler, and this is the place to do it. All the best to you. YOu know that every woman on this board is pulling for you.

[StephN]

Dear Julierene -
Not sure where in Texas you are being treated right now, but it looks like the treatment Lani is suggesting is at Stanford. You may not have the means to go to California. I see no harm in running this possibility past your team. They may know nothing about it, but at least you can bring it to their attention.

You would need an open surgery to remove the larger tumor to send a speciman for testing. These surgeries are normally easy to tolerate and nearly painless. This would depend on the location of that tumor.

Treatment with radioactive iodine should not result in hair loss.

Having had brain mets myself, I know exactly what it feels like to want to get on with something to knock them out. Plus you have this other p53 trial pulling you forward. It is all overwhelming, but we DO have some choices now instead of being railroaded into the old standard treatments.

If I understand correctly you have numerous small specks and one that is about 1/2" in diameter. Seems they want to give WBR as too many to treat individually. Perhaps the larger one should be treated with Gamma knife as well, if you do not take the route Lani is suggesting. This two part treatment by radiosurgery is often done.

Dear Julierene, take a deep breath and try to find a moment of peace. Some people believe that things happen for reasons that are not always clear at the time, so maybe there is a window of opportunity that will open for you. That is my fervent wish for you.

[ElaineM]

Lean on us whenever things get tough. Try to stay positive and keep putting one foot in front of the other.
Believe that you are going to be okay. Hugs !!

[julierene]

Yes, they put me on steroids. 4mg three times a day. I took in the article, and they felt like the WBR was the best route b/c of all the little spots. They feel 80-90% sure that this will buy me the time I need to start the trial in early December. However, now I worry about the bone mets in my back and hip, and the stuff in my liver. It's 4 more weeks to wait, where 4 was already enough - as we can all see.

I talked with the experiential researcher today and he told met this was the right thing to do. We don't know if the experimental drug will go through the blood/brain barrier - none of the mice got it in their brains. They practically got it everywhere else, being born with Li-Fraumeni Syndrome. But the mice lived normal life-spans after the treatment, so I just wanna be a mouse right now.

My p53 overexpression has been known for about 5 years now, but I know that it doesn't really work. So the idea that they can put a wild-type functioning p53 tumor suppressor gene into my cells seems like such a novel approach they have been working on for all these years.

Many of the test subjects that went before me were good guesses as to who might be p53 positive, but none were confirmed and only one out of about 12 have even responded with 5 weeks of stable disease. I'm not too sure how I feel about it, but I actually have the perfect diagnosis to test it on. These people may not even have a p53 deficit in their tumor cells, where I have it in every single cell in my body. It's a systematic mutation and gene deficit. It makes so much sense right?

Just getting the p53 in there has been one of the biggest challenges, and now it seems like they finally got a good delivery in a fat liposome delivered with nanoparticle technology, that doesn't get eaten by the body's immune system before it makes it to it's destination. I want the treatment so bad, it was excruciating to wait 4 weeks with no treatment. Now I have to wait 4 more weeks.

I finally got excited for the first time back in September when I got approved, and the thought actually occurred to me "Maybe I shouldn't have cashed out my 401K". I never looked back on that decision until about a week after I got accepted into the trial. Now I feel like i've got this huge hurtle to go through trying to gamble again with another 4 weeks. I guess I have to count my blessings, they were saying I might have to wait 4 more weeks after the radiation to get started.... and I knew I didn't have 12 weeks to be waiting around to start this with nothing but WBR inbetween.

I was thankful that they waived the 4 week period. I already put my life in their hands for 4 weeks, and I have very little options left. I have 3 young children depending on me, with a moron ex-husband and his new little wife trying to take over my position as their new mom.

I just wanted to give a big BIRD to them and say, "I'm not going anywhere, you're not going to get any life insurance from me, and I hope you won't get any Social Security from me either!" The bum wouldn't work no matter how hard I tried, until he got his new little wife. Strung me along for 3 years with no job, making me work through chemo with barely any salary, refusing to work... it was the worst. He just got married in June of this year, and said "Before I get married, I need to repent for my sins. I cheated on you 9 years ago after our second daughter was born back in 2000."

After being divorced for 2 years, he finally decided to tell me why he gave up on our marriage? When I asked him why he did it, he said "because I knew i could." He KNEW he could? I said, "No, you couldn't. You were married. I loved you and cherished you. Why?! Give me a real reason." He never would, and he blamed me for being manipulative, hateful, vindictive, and hoped that I would "wallow in my own anger" at what he did because I wanted all my questions answered. Said he "couldn't remember" tons of things about how it happened, if he flirted with her, why he took her to his work between classes on a Saturday, why he put her in his car knowing she had a cheating husband too, could have exposed me to STD's.

I will likely never get the answers, and his new little Mormon wife totally accepted him knowing all this and knowing what all he has done to me. How can someone love someone else who does that to another? I am still dealing with so much hurt from all that and how I feel I wasted 12 years of my life on him.

I now have a wonderful boyfriend that I really love though, so I can't really complain. He cares more about me than my ex ever seemed to. I just look back and wonder why I ever got involved with him, and I can only see my mistakes as just being vulnerable to his lies. He lied so well, I hardly didn't believe he really cheated. I thought maybe he just wanted me to stop asking why he divorced me and made up the story to anger me and satisfy me. But it wasn't so, he actually did it "because he could".

I feel like he just robbed me of some of the best years of my life, and all I have left is the sick ones for my relatives and friends. I hate him for doing that to me and I don't know if I can ever forgive him.

[Jackie07]

Julierene,

I will keep you in my prayers during your WBR. You might feel weak after a while.

[julierene]

A little foggy, but the weird "blue light" and smell of chlorine seems like a rare side effect.

[MJo]

Don't worry about foregiveness. Stay militant. Channel that anger into obliterating those brain mets. A blue light and smell of chlorine...Weird. Hope it's the wonderful aroma of dying cancer cells! All the best..

[julierene]

Yeah, I figure the biggest BIRD I can give my ex is to stay alive.

Not a very common side effect at all either. That is my hope, every time I get some strange pain or sensation, I seem to have good results - which is almost every successful treatment.

Yeah, forgiveness is a long ways away - if at all. I find infidelity one of the hardest most devastating things to try to overcome in a marriage. I just never expected my ex to do that to me, never-in-a-million-years. I tried so hard to be a great mom and wife... I wasn't always perfect, but I sure can't fault myself for not really being adequate enough to keep him from straying. I never denied him, and rarely snuffed off his needs. We had a pretty awesome and healthy sex life too... Go figure?

[Rich66]

Noting you were ER- before Herceptin. I just posted a reminder that it could have changed. Would Tamoxifen exclude you from trial? Might help you regardless of ER status.

If handy, please post a link to your p53 trial.

[Joan M]

Julierene,

I echo Lani and Steph on removing the 1.2 cm tumor and sending it for testing to Stanford University.

I am in the process of having a sample sent there now, even though my brain tumor was HER2-. There's a 10%-15% chance that a metastasis is discordant with the primary, according to my oncologist. However, I'd like the test done anyway just to find out whether I might be a candidate for radioactive iodine treatment for any future brain mets.

Sending you a lot of hugs,

Joan

[julierene]

I already had my ovaries removed, because I had a DCIS bilateral cancer on the other side that was PR+ (I think). What good would ER+ meds be in my brain mets?

[Lani]

Estrogen DOES cross the blood brain barrier and just because your ovaries were removed doesn't mean you are not making estrogen to feed your tumor.

Even with your ovary removed, your body makes estrogen (from testosterone) in your liver, muscles and fat AND most importantly locally around your breast (for the primary) and even perhaps around your mets. It seems the breast cancer tumor cells and their surrounding stroma cells may have a thing going where they can cause testosterone locally to turn to estrogen and AROMATASE is only ONE OF THREE ENZYMES that can help them do it. Even AIs only block one of the three enzymes.

Tamoxifen may have more actions than just sitting on the estrogen receptor and blocking it

So removing your ovaries does not prevent Estrogen from fueling growth of breast cancer.

If you don't think estrogen crosses the blood-brain barrier, then you must think men and women think alike!

Just joking...

[chrisy]

Julie,

Sorry, but I have to disagree with Rich on the Tamoxifen. Unless you are retested and find there is ER+ cancer, tamoxifen is not recommended and COULD possibly hurt. There is some evidence that tamoxifen can upregulate Her2.

And you are right - living (especially if you can do it well!) is the best revenge. HA!

Stay focused on that. Never blame yourself for your ex's dishonorable behavior. He does not deserve your forgiveness...it is yours to offer or not, and he won't care a whit anyway. You have every right to feel anger at his betrayal.

Forgiveness, if you choose to try and go there, is about releasing a burden off your shoulders not his.

I'm holding you in my prayers and wrapping you in love as always, but especially now.

Chris