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Late treatment with letrozole can reduce
breast cancer recurrence risk
Therapy beginning long after
stopping tamoxifen still offers preventive benefits
BOSTON - March 10, 2008 - Treatment with the aromatase inhibitor
letrozole (Femara) can reduce the risk of breast cancer recurrence
even when initiated one to seven years after a course of tamoxifen
therapy. The results of a study involving women originally in the
placebo arm of an international trial of letrozole will appear in
the Journal of Clinical Oncology and are receiving early
online release. Among those who chose to begin letrozole treatment
after the initial trial was halted, the risk that their cancer would
recur was cut in half compared with those who never received letrozole.
In addition, the risk of metastasis was 60 percent lower with letrozole,
and the chance that a new tumor would develop in the unaffected
breast dropped more than 80 percent.
"It appears that estrogen-sensitive tumors remain hormone
dependent and that patients' survival can be improved with careful
use of aromatase inhibitors, even many years after completing tamoxifen
treatment," says Paul E. Goss, MD, PhD, director
of Breast Cancer Research at Massachusetts
General Hospital Cancer Center, who led both the current study
and the earlier investigation, called the MA.17 trial. "These
results can be put into practice right away to improve the outlook
for women treated for receptor-positive breast cancer."
Letrozole is one of a class of drugs called aromatase inhibitors
that suppress the production of estrogen, which stimulates the growth
of breast tumors expressing the estrogen receptor. The most widely
used estrogen-blocking drug is tamoxifen, but the benefits of tamoxifen
treatment drop significantly after five years, while the drugs'
side effects continue.
The original MA.17 trial, conducted through the National Cancer
Institute of Canada, was designed to test whether letrozole could
reduce tumor recurrence and increase survival in breast cancer patients
who had completed five years of tamoxifen treatment. The study was
halted in October 2003 - a year earlier than planned - when interim
data analysis showed that tumors of women taking letrozole were
significantly less likely to recur. The final
analysis of MA.17 data, published in the September 7, 2005 Journal
of the National Cancer Institute, confirmed that women taking
letrozole had significantly better disease-free survival than those
taking a placebo.
Since women who received letrozole in the MA.17 trial began taking
the drug within a few months of stopping tamoxifen treatment, letrozole's
current approval restricts the initiation of therapy to the first
three months after tamoxifen discontinuation. However, participants
in the placebo arm of the MA.17 trial were offered the opportunity
to begin letrozole treatment when that trial was halted, which gave
investigators the opportunity to determine whether those women could
also benefit from the drug.
The current study analyzes data on more than 1,500 women from the
placebo group who chose to take letrozole and about 800 who chose
no further treatment. Almost three years after the MA.17 trial was
halted and letrozole offered, those who began letrozole therapy
had only a 2 percent risk of tumor recurrence, compared with almost
5 percent in those choosing no treatment. The risk of death from
breast cancer during that period was cut in half in those receiving
letrozole. Treatment also reduced the risk of metastasis by 61 percent
and appeared to prevent development of a new tumor in the opposite
breast by 82 percent.
The research team notes that this study is limited by the fact
that participants choose whether to take the drug themselves and
were not randomly assigned. While a randomized clinical trial would
more conclusively determine the benefit of letrozole treatment for
those who have been off tamoxifen for several months or years -
or even those who never took the drug - the results of this study
can help guide physicians and patients in deciding whether letrozole
therapy would be appropriate.
"Every patient who has previously taken tamoxifen should discuss
these new results with her oncologist. The risk that hormone-dependent
breast cancer will recur continues indefinitely, and our results
imply that aromatase inhibition is effective whenever initiated,"
says Goss, a professor of Medicine at Harvard Medical School
The current study was supported by grants from the Canadian Cancer
Society, the National Cancer Institute of Canada, the U.S. National
Cancer Institute and Pharmacia Corp. Novartis Pharmaceuticals, which
markets letrozole under the brand name Femara, also supported and
provided study medications for the initial MA.17 trial and the current
study.
Co-authors of the JCO study are James Ingle, MD, Mayo Clinic; Silvana
Martino, DO, Angeles Clinic and Research Center; Nicholas Robert,
MD, Inova Fairfax Hospital, Falls Church, Virginia; Hyman Muss,
MD, University of Vermont; Martine Piccart, MD, Institut Jules Bordet,
Brussels; Monica Castiglione, MD, University of Bern; Dongsheng
Tu, PhD, Lois Shepherd, MD, Michael Palmer, MSc, and Joseph Pater,
MD, National Cancer Institute of Canada Clinical Trials Group; Kathleen
Pritchard, MD, Toronto-Sunnybrook Regional Cancer Centre; Robert
Livingston, MD, University of Washington; Nancy Davidson, MD, Johns
Hopkins Hospital; Larry Norton, MD, Memorial Sloan-Kettering Cancer
Center; Edith Perez, MD, Mayo Clinic, Florida; Jeffrey Abrams, MD,
National Cancer Institute; and David Cameron, MD, Western General
Hospital, Edinburgh.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Stacy
Neale, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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