Women who received letrozole for 5 years after prior tamoxifen treatment in a randomized phase III clinical trial had a 34 percent lower risk of recurrence than those who received a placebo. The study found that postmenopausal women with early breast cancer benefit from extending treatment with aromatase inhibitor (AI) therapy with letrozole (Femara) from 5-10 years (Abstract LBA1).
Canadian Cancer Trial Group led the study, which was presented in a plenary session at the 2016 American Society of Clinical Oncology Annual Meeting.
“Women with early-stage hormone-receptor positive breast cancer face an indefinite risk of relapse,” said lead study author Paul Goss, MD, FRCP, PhD, Director of Breast Cancer Research at Massachusetts General Hospital in Boston, and Professor of Medicine at Harvard Medical School. “The study provides direction for many patients and their doctors, confirming that prolonging aromatase inhibitor therapy can further reduce the risk of breast cancer recurrences. Longer AI therapy also showed a substantial breast cancer preventative effect in the opposite, healthy breast.”
The ASCO expert in breast cancer, Harold J. Burstein, MD, FASCO, said 10 years of any therapy is significant.
“Fortunately, most women tolerate extended treatment reasonably well with few side effects. Now women can talk with their clinical team and make informed decisions to extend adjuvant endocrine therapy, or not,” Burstein said. “These data are important to the millions of women around the world with ER-positive breast cancer and suggest that longer durations of widely-available therapy reduce the risk of cancer recurrence, and prevent second cancers from arising.”
Although overall survival was not markedly different in the two groups of the study, Goss explained that finding may be due to the slow chronic relapsing nature of hormone-receptor breast cancer. With that factor, overall survival has proved difficult to demonstrate in clinical trials. As a result, regulatory approval for most endocrine therapies has been based only on improvement of disease-free survival.
Quality of Life Assessment
Patient overall quality of life was also studied in the trial. It was found to be comparable between the two groups.
“A large proportion of women with early breast cancer are long-term survivors. As hormone therapy is given over a long period of time, measuring how women feel is very important,” said Julie Lemieux, lead author of the analysis of patient reported outcomes from the study and also a researcher at the Centre hospitalier universitaire de Quebec in Canada.
The trial consisted of 1,918 postmenopausal women who had received 5 years of any one of three AI therapies as initial treatment or any duration of tamoxifen. Patients were allowed to enroll in the study for up to 2 years after completing previous AI therapy, but approximately 90 percent began receiving letrozole or placebo within 6 months of completing it.
Moderator and ASCO President Julie M. Vose, MD, MBA, FASCO, University of Nebraska Medical Center in Omaha, said, “It's really important that we consider quality of life with all of these types of studies. Make sure we consider what patients are going through.”
For the quality-of-life assessment, patient-reported data was measured with the standard SF-36 questionnaire, focusing on physical and mental health. A second questionnaire, MENQOL, was used to study menopause specific elements. Initial quality-of-life assessments were completed by 1,428 of the 1,918 participants. The assessments were repeated at 12, 24, 36, 48, and 60 months, with more than 85 percent of women completing the questionnaires at follow-up.
In both groups, no significant differences in quality of life or menopause-specific quality of life were found. Small differences in physical role functioning were found in favor of placebo, but were not assessed as clinically meaningful.
Among the key findings is a 34 percent lower risk of breast cancer recurrence for women in the extended letrozole group. The letrozole group also showed a lower annual incidence of contralateral breast cancer (0.21% vs. 0.49%) indicating a prevention effect. At 5 years of follow-up, 95 percent of women in the letrozole group were breast cancer free, compared with 91 percent in the placebo group.
The results of the trial may have significant benefit for the patient population. In 2012, more than 6 million women worldwide survived at least 5 years after a breast cancer diagnosis and the majority had ER-positive breast cancer.
Romi Herron-Cologna is a contributing writer.