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Lani · 11-02-2009, 09:18 AM

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.

11-02-2009, 09:18 AM	#3
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	Re: Waiting on Trail, got Brain Mets... 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.