Remember Lani's Na/I symporter test post?

[Joan M]

I sent a sample of my lung tumor to Stanford University and it tested positive for the iodide symporter.

Lani's post referred specifically to bc brain mets, but as it turned out, the PI wanted any bc met.

I tried to send a sample brain met from my Oct. 2008 craniotomy, but it didn't work out. At first, Stanford didn't receive enough, and another sample could not be sent because the other blocks were preserved in such a way as to exclude them from testing (preserved in OTC, rather than in paraffin).

Since that didn't work, I had a sample of my lung nodule from April 2007 sent, and it tested positive for the symporter.

However, each nodule might have a different result, such as when my lung nodule tested HER2+ positive but my brain nodule tested HER2-. So, a sample always has to be tested for whether it's Na/I symporter positive.

Even though I was positive, I was not eligible for the next step because I have no measurable disease. The next step would have been to determine whether a tracer lights up anywhere and then step three would have been to treat it with the iodide. And I guess they wanted bc patients with disease that's already showing up in scans. The Na/I symporter test for bc is similar to that for treating thyroid cancer.

The PI's research assistant told me yesterday that if I develop another nodule that's biopsied, I can send another sample for as long as the study is still being conducted. Keep this in mind. I got the impression that they're looking for as many samples as possible.

This is a pilot study, and the details can be found under NCT00568438 at clinicaltrials.gov. In short, the PI is looking for another way to treat bc, especially for women who are triple negative. Also, the symporter crosses the blood brain barrier (BBB).

I'm not sure whether I've used the word symporter correctly, etc., but this basically explains it.

Joan

[Rich66]

Sounds kind of Sc-fi. Hope it delivers non-fiction results.

[Ellie F]

Thanks for the posting Joan.It does sound a bit sci-fi but sometimes these shifts in thinking are just whats needed. If a patient is suitable and progresses to stage 3 is it the iodide that 'kills' the cancer cells or is something attached to it as in heceptin and t-dm1?
Ellie

[Joan M]

Yes. It's sounds kind of out of this world, and it would be heavenly if something of clinical significance came out of it.

I believe it's the radioactive iodide that kills the cancer cells, not attached to anything. Also, you would have to be stage 4, at least for the trial.

Joan

[Lani]

Glad to hear you made contact with these people. Sorry you couldn't participate, but glad that you have no measurable disease to allow participation. It would be great if this pans out!!!

[Ellie F]

Hi again
just read article about nimotuzumab linked to a radioactive body. This would potentially be a great leap forward. Just imagine a targeted treatment selective to only the bad cells!! Let the sci-fi era of bc treatment commence..
Ellie

[Rich66]

Here's the study LINK (http://clinicaltrials.gov/ct2/show/NCT00568438)..with a err..slightly less than extensive explanation:

Detailed Description: The objective of the study is to further understanding of proteins that occur in both normal cells and tumor cells and to learn more about certain diseases and potential alternative treatments for these diseases.

Seriously. This is the leanest study page I've seen. Where's the beef?

[Joan M]

I would agree. The clinical trials information at clinicaltrials.gov is sparse. But here's some information that I cut and pasted from the pdf permissions file Standford University sent me for step 2 of the trial. That is, after I tested NIS positive, but before they decided that I needed to have measurable disease to participate in the next step. The third step is treatment (administering iodide 131I).

****
STANFORD UNIVERSITY - Research Consent Form
Protocol Title: A Pilot Study to Determine Radioiodide Accumulation and Dosimetry in Breast Cancers Using 124I PET/CT
Protocol Director: Irene L. Wapnir, MD
IRB Approval Date: November 18, 2009 IRB Expiration Date: November 17, 2010

Are you participating in any other research studies? _____ Yes _____No

A research study is designed to answer specific questions, sometimes about a drug’s or device’s safety and effectiveness. Being in a research study is different from being a patient. When you are a patient, you and your doctor have a great deal of freedom in making decisions about your health care. When you are a research participant, the Protocol Director and the research staff will follow the rules of the research study (protocol) as closely as possible, without compromising your health.

You are invited to participate in this research study because you have breast cancer. This clinical research study is designed to help find out whether iodide transport is present in breast cancers and determine the feasibility of treating patients like you with radioactive iodide. The secondary goal of this study is to calculate the amount of iodine concentrated in your tumor(s) to estimate whether radioactive iodide (a form of iodine called 131I used to destroy thyroid cancer cells) could be used.

You were selected as a possible participant in this study because your tissues have been tested for the iodide carrier protein called the sodium iodide symporter or NIS (NaI symporter). This does not represent genetic testing. Your participation in this study is entirely voluntary.

Your decision whether or not to participate will not prejudice you or your medical care. If you decide to participate, you are free to withdraw your consent, and to discontinue participation at any time without prejudice to you or effect on your medical care. If you decide to terminate your participation in this study, you should notify Irene Wapnir, MD.

This research study is looking for a total of 10 women who have breast cancer and whose tissues have tested positive for NIS. This study is funded by the Stanford Center for Clinical and Translational Education and Research (SCCTER) and will occur at the Stanford University only.
****
The rest of the consent form describes how step 2 unfolds.

Joan

[Rich66]

Not sure if this is the same approach..maybe augments the previous..but looks interesting:

Breast Cancer Res Treat. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Breast%20Ca ncer%20Res%20Treat.%27%29;) 2010 Mar 9. [Epub ahead of print]
The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS).

Fortunati N (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fortunati%20N%22%5BAuthor%5D), Catalano MG (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Catalano%20MG%22%5BAuthor%5D), Marano F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Marano%20F%22%5BAuthor%5D), Mugoni V (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mugoni%20V%22%5BAuthor%5D), Pugliese M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Pugliese%20M%22%5BAuthor%5D), Bosco O (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bosco%20O%22%5BAuthor%5D), Mainini F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mainini%20F%22%5BAuthor%5D), Boccuzzi G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Boccuzzi%20G%22%5BAuthor%5D).
Oncological Endocrinology, AOU San Giovanni Battista, University of Turin, Turin, Italy.
New drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G(2)/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease.

PMID: 20213084 [PubMed - as supplied by publisher]

[Ellie F]

Thanks Joan and Rich for digging out this info.

Joan-would you seriously consider this option if you needed more treatment?
BIG FINGERS X YOU WON'T NEED IT
Ellie

[Joan M]

Rich, I think that probably several people are working on the same idea or similar approaches, which seems common in cancer research and is good for us.

Ellie, Yes, I would certainly consider a radioactive iodide treatment if it showed promise. And thanks for the crossed fingers! I'm always doing that, too!

Joan