Thursday, October 09, 2003
A Canadian-led international clinical trial
has found that post-menopausal survivors of early-stage breast cancer who
took the drug letrozole after completing an initial five years of tamoxifen
therapy had a significantly reduced risk of cancer recurrence compared to
women taking a placebo. The results of the study appear in today's advance
on-line edition of the New England Journal of Medicine.
The clinical trial has been halted early
because of the positive results and researchers are notifying the 5,187 women
worldwide who have participated in the study. Women on letrozole will continue
taking the drug and those on the placebo can begin taking letrozole, if they
wish.
"This very important advance in breast
cancer treatment will improve the outlook for many thousands of women," said
Andrew von Eschenbach, M.D., director of the National Cancer Institute which
led the study in the United States. "This is one more example of the ability
to interrupt the progression of a cancer using a drug that blocks a crucial
metabolic pathway in the tumor cell."
Study researchers found that letrozole,
when taken after five years of tamoxifen therapy, substantially increased
the chance of remaining cancer free. In total, 132 women taking the placebo
had their disease recur compared to 75 on letrozole. Overall, letrozole
reduced the risk of recurrence by 43 percent, so that after four years of
participating in the trial, 13 percent of the women on the placebo, but only
seven percent, of those on letrozole had recurred. Deaths from breast cancer
were also reduced. Seventeen women taking the placebo died of breast cancer
compared to nine taking letrozole.
While tamoxifen is widely used to prevent
breast cancer recurrence in post-menopausal women, it stops being effective
after five years because, researchers believe, tumours become resistant to
it.
"More than half of women who develop
recurrent breast cancer do so more than five years after their original diagnosis,"
says Paul Goss, M.D., of Princess Margaret Hospital in Toronto. "For years,
we have thought that we had reached the limit of what we could do to reduce
the risk of recurrence with five years of tamoxifen. Our study ushers in
a new era of hope by cutting these ongoing recurrences and deaths from breast
cancer after tamoxifen by almost one half." Goss, a leading expert in novel
hormone therapies for the treatment and prevention of breast cancer, conceived
and chaired the international trial with letrozole.
A form of hormone therapy for the treatment
of breast cancer, letrozole works by limiting the ability of an enzyme called
aromatase to produce estrogen, a major growth stimulant in many breast cancers.
Mayo Clinic medical oncologist James
Ingle , M.D., says, "Based on our findings, all post-menopausal women with
hormone-receptor positive tumours completing about five years of tamoxifen
should discuss taking letrozole with their doctors to reduce their risk of
breast cancer recurrence." Ingle, from Rochester, Minn., led the research
study in the United States.
With Canadian Cancer Society funding,
the clinical trial was coordinated by the National Cancer Institute of Canada
Clinical Trials Group at Queen's University, in partnership with the U.S.
National Cancer Institute and its Clinical Trials Cooperative Groups. Novartis,
which manufactures letrozole, also known as Femaraź, provided the drug for
the trial.
Women participated in the study for
an average of 2.4 years and for as long as five years. The study found that
women taking letrozole had a reduction in the number of recurrences of cancer
in their previously affected breast, a reduction in the number of new cancers
in their opposite breast, and a reduction in the spread of the cancer outside
their breast.
The side effects of letrozole, a pill
which is taken once a day, are very similar to those experienced by women
undergoing menopause. They were generally mild in study participants. Women
in the study will continue to be followed to more thoroughly assess any effects
of long-term use of letrozole on bone strength or other organs. Until these
are known, patients should be monitored closely.
"The Canadian Cancer Society is pleased
to have made a key contribution to this study," says Barbara Whylie, M.D.,
director of Cancer Control Policy for the Canadian Cancer Society. "We estimate
that more than 20,000 Canadian women will be diagnosed with breast cancer
this year and just over half of those are going to be eligible for this drug.
That means these women will have a significantly improved hope for a future
without cancer."
"This large trial only began in 1998
and we already have important results that will change clinical practice,"
says Jeffrey Abrams, M.D., coordinator of the U.S. National Cancer Institute's
Cooperative Group breast cancer treatment trials. "This is a tribute to
the patients and physicians who participated since their efforts will now
have a positive impact on so many lives."
Participants in the clinical trial were
enrolled through hospitals, cancer centers and institutes throughout Canada,
the United States, England, Belgium, Ireland, Italy, Poland, Portugal and
Switzerland. The European Organization for Research and Treatment of Cancer
and the International Breast Cancer Study Group coordinated the European
component of the trial.
The Canadian Cancer Society is the largest
charitable funder of cancer research in Canada. It funds clinical trials
research through its support of the National Cancer Institute of Canada Clinical
Trials Group.
The National Cancer Institute is the
primary U.S. agency for cancer research.
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For more information on the results of this clinical
trial and what it might mean for you:
A Q&A on this finding can be found at: http://cancer.gov/newscenter/pressreleases/letrozoleQandA
More information on aromatase inhibitors can be found
at: http://cancer.gov/clinicaltrials/developments/aromatase-inhibitors-digest
In Canada, call the Canadian Cancer Society at 1-888-939-3333,
Monday to Friday, 9 a.m. to 6 p.m., or visit www.cancer.ca. Service is available in
English and French.
In the United States, call the National Cancer Institute'
Cancer Information Service at 1-800-422-6237, Monday to Friday, 9 a.m. to
4:30 p.m. or visit cancer.gov. Service
is available in English and Spanish.
