Copper Depletion Therapy Keeps High-Risk Triple-Negative Breast Cancer at Bay

NEW WEILL CORNELL STUDY SHOWS ANTI-COPPER DRUG MIGHT PREVENT THE SPREAD OF CANCER TO ORGANS

Folks, this is very important news...

The last time I posted was in June, shortly after starting to take TM, the drug discussed in the press release below. I've been taking it since then. It took a long time to bring my copper levels down, but they are where they need to be now and I'm in a holding pattern, expecting this to work.

So, if you know anybody diagnosed with triple negative breast cancer (no hormone connections), please pass this along. It could prolong or save a life. And it doesn't even cause side effects...unless TM is responsible for all those new dark hairs I'm finding among the white.

NEW YORK (February 13, 2013) — An anti-copper drug compound that disables the ability of bone marrow cells from setting up a "home" in organs to receive and nurture migrating cancer tumor cells has shown surprising benefit in one of the most difficult-to-treat forms of cancer — high-risk triple-negative breast cancer.

The median survival for metastatic triple-negative breast cancer patients is historically nine months. However, results of a new phase II clinical trial conducted by researchers at Weill Cornell Medical College and reported in the Annals of Oncology shows if patients at high-risk of relapse with no current visible breast cancer are copper depleted, it results in a prolonged period of time with no cancer recurrence. In fact, only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after using the anti-copper drug, tetrathiomolybdate (TM).

"These study findings are very promising and potentially a very exciting advance in our efforts to help women who are at the highest risk of recurrence," says the study's senior investigator, Dr. Linda Vahdat, director of the Breast Cancer Research Program, chief of the Solid Tumor Service and professor of medicine at Weill Cornell Medical College.

Dr. Vahdat says four of the study participants with a history of metastatic triple-negative breast cancer have had long-term benefit remaining disease free for between three and five and a half years.

"The anti-copper compound appears to be keeping tumors that want to spread in a dormant state," reports Dr. Vahdat, who is also medical oncologist at the Iris Cantor Women's Health Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "We believe one of the important ways it works is by affecting the tumor microenvironment, specifically the bone marrow-derived cells that are critical for metastasis progression."

In addition, study participants with other forms of high-risk for relapse breast cancers — either stage 3 or stage 4 — without evidence of disease after treatment have also fared well. The progression-free survival rate among these 29 patients in the study has been 85 percent, to date.

"As good as these interim findings look to us, we cannot talk about significant benefit until we compare TM treatment to other therapies," she says. Dr. Vahdat expects to launch a phase III randomized clinical trial in the near future.

This research is a report of the first 40 patients. The clinical trial, which began in 2007, has been expanded many times and now includes 60 patients, more than half of who have triple-negative breast cancer.

DEPLETE COPPER TO PREVENT CANCER SPREAD

New discoveries in the science of metastasis and examination of the body's utilization of copper to promote cancer spread led to this clinical trial.

Investigators at Weill Cornell, including some of this study's co-authors, have contributed to the recent understanding of the role bone marrow cells play in promoting metastasis. They previously found that a collection of bone marrow-derived cells, which include VEGFR1+ hematopoietic progenitor cells (HPCs), prepare a site in distant organs to accept cancer cells. HPCs also recruit endothelial progenitor cells (EPCs), among others, to activate an "angiogenic switch" that establish blood vessels at the site to feed newly migrated cancer cells.

Breast cancer research studies conducted at Weill Cornell have also found that immediately prior to cancer relapse, levels of EPCs and HPCs rise significantly further, suggesting that the EPC target of the copper depletion approach is one that makes sense.

"Breast tumors want to move to specific organs, and these EPCs and HPCs cells leave a 'popcorn trail' for cancer cells to follow, as well as provide the building blocks for blood vessels to greet them as they arrive," Dr. Vahdat says.

Copper is critical to mobilizing these cells. Copper is essential to the metastatic process. It is a key component of enzymes that help turn on angiogenesis in the tumor microenvironment, and it also appears to play a role in directing cancer cell migration and invasion, according to researchers.

TM is a copper chelation compound used to treat Wilson's disease, a hereditary copper metabolism disorder, and has been studied in phase I and phase II clinical trials for a number of disorders. Animal studies have demonstrated that depleting copper decreases proliferation of EPCs, as well as blood vessel formation and tumor growth.

Dr. Vahdat's study is the first human clinical trial to utilize a copper depletion strategy to modulate EPCs in breast cancer patients with an extraordinarily high risk of relapse from hidden residual disease. Most of the studies in other solid tumors with visible advanced disease have been disappointing, say researchers.

Despite improvements in breast cancer therapy, there is significant risk of relapse in a high-risk subset of patients. The risk of relapse in stage 3 patients is 50-75 percent over five years, and patients with stage 4 breast cancer always recur. Triple-negative breast cancer patients have a poorer prognosis even when diagnosed in early disease stages.

"These triple-negative patients represent a substantial proportion of metastatic breast cancer patients," says Dr. Vahdat. "These are the patients that need the most attention, which is why we have focused most of the resources of our Metastases Research Program on this problem."

In the study, researchers found that 75 percent of patients achieved the copper depletion target using TM after one month of therapy, and that copper depletion was most efficient (91 percent) in patients with triple-negative tumors, compared to other tumor types (41 percent). In copper-depleted patients only, there was a significant reduction in EPCs, and the 10-month relapse-free survival was 85 percent. In addition, TM was found to be safe and well-tolerated in patients.

The study shows copper depletion appears to inhibit the production, release, and mobilization of EPCs from the bone marrow, leading to a suppressed angiogenic switch and tumor dormancy.

"There are a lot of cancer experts at Weill Cornell working very hard to understand this precise mechanism, define the clinical benefit in this ongoing copper depletion drug clinical trial, and determine its future study," says Dr. Vahdat. "Keeping cancer dormant is what we all want for our patients — especially triple-negative breast cancer patients at highest risk of recurrence."

Study co-authors include Dr. Sarika Jain, Maureen M. Ward, Naomi Kornhauser, Dr. Ellen Chuang, Dr. Tessa Cigler, Dr. Anne Moore, Diana Donovan, Christina Lam, Marta V. Cobham, Sarah Schneider, Sandra M. Dr. Hurtado Rúa, Celine Mathijsen Greenwood, Dr. Richard Zelkowitz, Dr. J. David Warren, Dr. Maureen E. Lane, Dr. Vivek Mittal and Dr. Shahin Rafii from Weill Cornell; Dr. Jules Cohen from Stony Brook University Cancer Center, Stony Brook, N.Y.; and Steven Benkert from NewYork-Presbyterian Hospital.

The study was funded by the grants from the Anne Moore Breast Cancer Research Fund, Stephen and Madeline Anbinder Foundation, Rozaliya Kosmandel Research Fund, Susan G Komen for the Cure, New York Community Trust, Cancer Research and Treatment Fund, Manhasset Women's Coalition Against Breast Cancer and Berman Fund.

WEILL CORNELL MEDICAL COLLEGE

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

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Nineteen

It’s been a long while since I’ve written a blog entry, in fact, almost a year. A lot has happened during that time, much of it concerning the cancer that started my fingers to blogging in the first place. I’ve learned a few lessons during the last year, and I’m still enjoying life in Oly, even on the days when it’s been far too long since seeing sunshine.

As you know, I’ve worked with a lot of alternative therapies to keep my body functioning well while undergoing treatment. And I’ve outlived the two other women I’ve known who had the same aggressive triple negative breast cancer. Despite my best efforts, the tumor continued growing and became more threatening, with indicators it had become inflammatory. This is pretty much a death sentence, so I’m lucky to still be here – and not only that, but feeling good and looking healthy.

One of the things I've learned is that PET scans, which show cancer cells that grow by feeding on sugar, aren't always accurate. I had four clear PET scans even though the tumor in my breast was continuing to grow. Apparently my tumor didn't get it's growth from glucose, but, just like normal cells, from oxygen. I only recently learned that cancer, or at least some cancers get energy just like normal cells, using oxygen. So much for the often touted "cancer can only grow in an oxygen-poor environment." 

Most alternative cancer treatments and cures rely heavily on the body’s ability to detoxify through the liver. As I described in post eleven  (http://wwwadifferentway-rebecca.blogspot.com/eleven), the genetic flaw, MTHFR, cuts down my ability to detoxify to somewhere between 10-30% of normal. So, while I really, really, really don’t like putting nasty chemo toxins into my body, adding even more to the burdens of my already struggling liver, I once more signed on for a round of chemo, to be followed by a mastectomy, starting last October.

I did find a doctor who isn’t opposed, and even encourages, the use of natural therapies to enhance the use of chemo drugs, so I was very pleased with Dr Ben Chue at Lifespring Cancer Treatment Center in Seattle. He impressed me at first because, after looking over my past paperwork for a few minutes, he seemed to remember everything he had read. Amazing! And on my first day of treatment I was quite surprised to see him talking with each patient who was being hooked up. He asked and answered questions and never seemed to be too hurried. Previous experience had shown me doctors who set the protocol up and turned it over to the nurses. To actually see the doctor and ask a question or two required an appointment. But Dr Chue was available every treatment day, and I really appreciated that.

Another reason I was happy with Dr Chue was because he had introduced metronomic chemotherapy in Seattle many years ago. Instead of giving a huge dose of the drugs every three weeks, he gave one third of the dose weekly. It meant a trip to Seattle almost every week from late October through early March, but it also meant I didn’t get as sick and weak as many cancer patients. He also used a most effective anti-nausea medication, Aloxi, as part of my weekly infusion. Aloxi works for five days, so I never had the unfortunate experience of being nauseated and unable to eat.

My hair began falling out like crazy just after Thanksgiving. Vacuuming the loose hair didn't help! So I went to Dave's barber and had him trim what was left back to half an inch. When that continued falling and getting into everything, I had Dave shave me bald! Yikes! Right in the middle of winter, it was back to wigs and caps. I really don’t like wearing a hot, itchy wig, and eventually gave it up in favor of caps and scarves tied into turban-like arrangements.

My biggest side effect was tiredness. By late December I spent a lot of days in the recliner. I’d get up feeling fine, eat breakfast and empty the dishwasher. Then I’d sit down in the recliner and wake up two hours later! I really do see the superiority of the Insulin Potentiation Chemotherapy (IPT) I had in Arizona in 2010. I actually had more infusions in the seven weeks I was there than I had this past winter, without the side effect of either nausea or tiredness, and without my immune system being compromised to the point where I couldn’t be treated. I did lose my hair, though most patients on IPT don't. But it was clear to me that much more of the drug went straight to the cancer cells and less of it went throughout my body. The tumor  responded quickly that time, but much less so this time. Of course, cancer is one tricky devil which often learns to adapt and become resistant to drugs, so perhaps that was the reason it responded less well this time.

On St Patrick’s Day I turned 70 and we had a big party for the occasion. What a delight to see so many old friends and relatives in one place, all to celebrate with me four days before the planned mastectomy. Friends gave me money for a spa day, and I’ve yet to treat myself to this pleasure, but I will soon. Scott flew in from London to help celebrate my birthday as well as to be here for surgery day. Erin, Katie and Keegan came from Enumclaw for the birthday party.

March 20 we drove to Seattle for surgery the next day. I had chosen a surgeon from the Seattle Cancer Care Alliance (SCCA) who operates at the University of Washington Hospital. A woman from Oasis had sent me several articles about how to help prevent the metastases that surgery often stimulates. I was prepared, and I requested a regional anesthetic, called a paravertebral block, which numbs the area of surgery with shots near the spinal cord. This meant I would need much less general anesthetic. As a result, I had none of the usual side effects, which are mostly caused by anesthesia and narcotic pain medication. In fact, over the next couple of weeks of recovery I had no pain to speak of, and never filled the prescription for Oxycodone.

Surgery wasn’t until 6 PM, and Dave and Scott finally saw me again about 9:30. It must have been a very long day for the surgeon, because I was originally scheduled for 5:30 AM. I was thankful for the schedule change, but amazed at how long the preparation for this type of anesthesia took. Still, it was well worth it!

The hospital was filled to 100+% capacity, so they wheeled me back to the pre-op area, where I spent the night in a tiny room, with Dave at my side in a recliner. The nurses were attentive and helpful, and I went home the next morning. Wow! Drive-by surgery. Practically. But I was feeling good and happy to be back in my own home.

So, the next big question is what to do to prevent a return of the cancer. Yes, there was still live cancer in the tumor, even after a round of chemo, and yes, it had spread to seven lymph nodes. Dr Chue wants me to continue chemo, but change the drugs. The SCCA folks want me to do radiation. The local oncologist, Dr Ye, thinks I should do both. But, I’m thinking, why put my poor body through more toxic chemicals and radiation, both of which stimulate new cancers?

As part of my research, I had an appointment with a medical oncologist at SCCA a couple of weeks ago, to see if there were any clinical trials of a specific nature that I might qualify for. The first doctor came in, read a summary of my medical report, and said, “We don’t see too many people like you.”

“No,” I replied, “I should be dead by now, right?” She agreed. Later, another oncologist came in and said they don’t really have a standard of care for someone in my situation. But, even so, they both thought I should have radiation and they made a couple of other suggestions.

Of course, in the perverse but usual way, I didn’t think of this at the time, but a couple of hours later, as we ate dinner, I told Dave, “You know, they were surprised to find me not only alive, but looking healthy. That tells me that what they are using on women with triple negative breast cancer isn’t working very well. Maybe instead of recommending the things they do, they should have been asking me what I’ve been doing to be as healthy as I am.” Dave agreed.

I’ve been working with David Lerner, an acupuncturist with a special interest and study of cancer. His recommendation was for a drug called Tetrathiomolybdate (TM), which takes excess copper out of the body. It turns out that, in order to grow, cancer cells require a lot of copper. Normal cells also need copper, but to a much lesser extent than cancer cells. So the idea is to remove excess copper and keep the levels high enough for normal function, but low enough so cancer cells, which may still be lurking, cannot grow and spread. So I’m doing that and hope to have my copper levels down sufficiently in another few weeks. It amazes me how easily we are all depleted in other minerals, but how long it takes to get rid of extra copper.

A year or so ago, as my search for cancer alternatives continued, I watched a film on my computer at the website www.phoenixtears.com. It is all about the healing power of cannabis oil, and how to make it. It sounded promising, but I didn’t have a clue where to buy the stuff, and when someone told me of a source, it was far too expensive for me to consider. However, the political climate around marijuana has changed dramatically in Washington State. I discovered I can now buy cannabis oil, with a doctor’s recommendation, at half a dozen dispensaries right here in Olympia. A syringe, which lasts about three weeks, costs $50 cash. No credit cards, no checks. So I’m now taking a dose, about the size of a grain of rice, every evening. The side effect? I’m sleeping like a baby!

Here’s the interesting thing. Marijuana comes in various types. The cancer-healing chemicals, cannabinoids (CBDs) are most prevalent in the Indica type, while Sativa carries the most THC – the stuff that makes you high. Not only that, but the CBDs actually counteract the THC to a degree. So I don’t get high. Dosing correctly has been problematic, but if I get too much I just don’t have a lot of ambition the next day. More recliner time!

Most of the research on cannabis and its’ ability to cure cancer and other diseases comes out of Israel and Spain. There is good research showing it kills cancer cells and prevents them from spreading. An excellent program to watch, originally on Wealth TV, but also found on Youtube, is Marijuana - Miracle Cure 2 www.youtube.com/watch?v=H8eybPn6cLU. So I’m counting on my two-pronged approach to keep me cancer free. I haven’t said no to further treatment, but I’m hoping to avoid putting my poor body through a chemical wringer once again. And besides, my hair is growing and I don’t have to wear caps and hats everywhere I go these days!