after reading post by Rolepaul on brain mets--repostr 4 those running out of options

[Lani]

Lani

for those with brain mets running out of options
I have previously written about the unusual approach of Dr. Irene Wapnir of Stanford against her2+ brain mets.

She has published that her2+breast cancer brain mets often have an additional feature called a sodium-iodine symporter. This is something that is apparently simple to test for on a biopsy of a brain met.

When present, it opens up the opportunity to try to treat the brain met(s) with a simple, safe, already FDA approved (against thyroid cancer) treatment consisting of radioactive iodine as I understand it.

They have to temporarily suppress your own thyroid glands secretion for a short time to make it work and that is totally reversible.

I was recently able to discover who best to contact about this possibility and as so many here recently have been plagued by brain mets with fewer and fewer additional options I thought it best to post again on this possibility.

Marilyn Florero, Breast Surgery, 650 724 1953. Email: florerom@stanford.edu
^^^^^^^^^^^
09-09-2011, 06:58 AM #2
Lani

Re: for those with brain mets running out of options
from my previous posts--

also as I understand it the trial accepts those who have had multiple other treatments in the past but there may be a limitation to how much radiation one has already received



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.


WHAT I PREVIOUSLY POSTED FOR HUTCHBK and Believe51

Have you had a brain biopsy of any of your brain mets? If so, you might want to send 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"

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
^^^

The last I heard, the pilot study is open and available--just need to test a specimen of the brain met for the NA/I symporter and be sure the maximum amount of radiation to the brain area has not already been given.

AS 80% of her2+ brain mets are NIS-positive, perhaps this information may prove useful to one/some of you

[NEDenise]

Lani,
Thanks for taking the time, and making the effort to post this again. You really are a treasure!
Denise

[tricia keegan]

Thanks Lani, I dont have brain mets (thankfully) but appreciate this info!

[Lani]

bumping this us so more may see

Lani

[hutchibk]

Thanks Lani! I still haven't (and won't) do WBR, we chose 'wack-a-mole' after we did 18 months on Tykerb/Xeloda, with an excellent response to both avenues.

I currently don't show any brain mets, but I do show a small pituitary spot (9mm) in a place that has had radiation twice to it... meaning I can't have anymore radiation there since the optic chiasm has had it's full share of radiation.

I wonder if this treatment in SF is an option, since this 9mm spot isn't in the brain, but more in the bony skull?

(all docs, about 8 of them, lean a little more towards radiation necrosis and not tumor, because of my history with the twice radiated cerebellum being necrosis and not tumor. They aren't starting at 0 though... they are starting at 50/50 and 'lean' necrosis, but aren't sure, so I am on watchful MRI waiting...)

[Rolepaul]

Excellent work. I hope that we get news on more patients. I know that there may be more than one way to attack HER+ brain mets, but the Herceptin intothe CNS with either IT or lumbar puncture have worked for individuals on this forum.

[Lani]

I never knew and do not remember all the details, but Courtney initially responded to IT herceptin but later progressed.......

Not trying to sound negative, but I think it always is good to feel there might be something in the back pocket...a plan B

[Rolepaul]

Courtney had a lower dosage amount. I have two back pockets and both have plans.

[Lani]

very glad to hear it (and discover more about Courtney)

You can never have enough pockets (back or otherwise) or plans

I like to say if you are prepared/ take along an "umbrella" it seems to be less likely to rain

With Plans A B C... hopefully you won't ever have to use them, just like the umbrella!

[Rolepaul]

Courtney I think also had it spread to other areas besides the brain. Nina is having those treateed with IV Herceptin and Navlebine. We saw abnormal cells in blood pulls, tumor markers were above normal, and other faint signs that there was a need for systemic treatment. Those are all back in normal ranges for serum based tests, and the blood cells are being run through an analyzer and no deformed cells are seen in 10,000. CNS fluid samples show noral glucose and protein, which were 40 for glucose and 555 for protein in January. These are being tracked with every IT treatment, currently at every two weeks.

I appreciate your concern, and have the same. A women treated at UCLA and currently in treatment at Cedar Sanai in Los Angeles is nearly four years out for treatment of LMD/brain HER+ mets and is doing great. There was only one other case besides Courtney where cancer returned in an IT Herceptin patient and that was in the liver. I am tracking the patients pretty well, as I did last December when it went to Nina's spine. There are still vaccine trials and other options to explore. MD Anderson has a very successful vaccine trial on going that we war elooking at.

Thank you again for your insight. I get some early info on the lab trials and sometimes see galley proofs before the release date. That helps with deciding what to do for Nina's treatment. I also have been known to edit an article or two for content.

Keep up the good work. I will try to get a couple more people from industry to go to this blog and see why they do the work they do.

[KDR]

Rolepaul, is it possible that someone with hemangioma (spelling?), non HER2 could be treat this way? I ask for a friend's husband.
Thanks
Karen

[yanyan]

Thanks Lani and Paul for putting in those great info on treating brain mets. Thanks Brenda for sharing your treatment history ! It really helps those who are in treatment and those who might store it as a bullet just in case.

[Rolepaul]

Update from the first of September: There is a slight change in the lumbar MRI that is unclear. There might be something at the L2-L3 area of nerves and a slight increase in die uptake where the lumbar puncture occurred. We bumped the IT Herceptin dose to 1.6 mg/kg, but want to go back to once per week to see if that removes the slight (neither doctor could see it) indications that were seen. The doctors are not even sure there is anything to worry about, but we want to be aggressive. Might think about Gamma knife to the spinal nerve in question. At least Nina is back in Raleigh and flying out as needed. That helps her spirits. New oncology hematology team her is more responsive to us as well. We might have some treatments local to lessen the travel.
Rolepaul

[KDR]

Hi, Paul,
It sounds a bit murky at this point, but you are taking pre-emptive steps, as you do, to be sure you stay ahead of the game.
Never a dull moment in this game. My scans are Wednesday. Will keep you in the loop, and my best goes to you and Nina.
Always,
Karen

[NEDenise]

Paul,
Keeping my fingers crossed, and sending prayers for Nina. Sounds like she's in good hands! And Karen...I'll be thinking of you on Wednesday too!
Hugs all around, friends!
Denise

[Lani]

at one conference I went to, one poster presenter from Sweden had already given humans radioisotope labeled affibodies (w herceptin-like targeting) and they seemed to cross the blood-brain barrier and identify brain mets (don't remember about leptomeningeal mets)

When and if this becomes available, it would help identify if these are indeed recurrences.

It was at either a ASCo or AACR annual meeting or ASCO or AACR BREAST MEETING (not sabcs as far as I recall) in the last 2.5 yrs I seem to think it might have been last yrs asco breast.

Don't know how far they have gotten with this...just a thought

[Rolepaul]

Nina is still going strong on the IT Herceptin and Topotecan, with IV Herceptin and Navelbine. No signs of abnormal cells in the blood or Ommaya fluid. The last MRIs showed two very small areas to keep under observation, but nobody really cannot tell what they are. They could be related to the lumbar puncture for one and to lower back issues on the other. Nina continues to do her yoga, drive, walk 5 miles a day (most of the time cracking the whip to get me to go), and even lew into Houston on Sunday, treatment on Monday morning, and back home Monday night so 8 hours on the planes in two days. Keep up the good vibes.

[schoonder]

Excerpt from prior post:

"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."

that discusses how common brain metastasis really is and scarcity of effective treatment options, makes one wonder why so little effort is currently expanded in improving upon this situation. Case in point, T-DM1 completed or about to complete 3 phase III trials in mBC, about to start a phase III in gastric her2+ cancer, but nothing as yet directed at this common occurring progression with this disease. Would think targeted approach, with little damage to non-cancerous tissue, provide a
great opportunity to evaluate this agent' s performance beyond the blood-brain barrier.
There probably are good reasons why NIH in conjunction with other governmental health agencies haven't pressured big pharma in more aggressively seeking better solutions for treatment.

[Pray]

Gods blessings to Nina. Please know that you both are in my prayers. Peace

[NEDenise]

Nina and Paul,
Think of you often...praying for good things to continue.
Denise