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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