A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer
Open accessAbstract
BACKGROUND: In hormone-dependent breast cancer, five years of postoperative tamoxifen therapy--but not tamoxifen therapy of longer duration--prolongs disease-free and overall survival. The aromatase inhibitor letrozole, by suppressing estrogen production, might improve the outcome after the discontinuation of tamoxifen therapy. METHODS: We conducted a double-blind, placebo-controlled trial to test the effectiveness of five years of letrozole therapy in postmenopausal women with breast cancer who have completed five years of tamoxifen therapy. The primary end point was disease-free survival. RESULTS: A total of 5187 women were enrolled (median follow-up, 2.4 years). At the first interim analysis, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the contralateral breast--75 in the letrozole group and 132 in the placebo group--with estimated four-year disease-free survival rates of 93 percent and 87 percent, respectively, in the two groups (P< or =0.001 for the comparison of disease-free survival). A total of 42 women in the placebo group and 31 women in the letrozole group died (P=0.25 for the comparison of overall survival). Low-grade hot flashes, arthritis, arthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding was less frequent. There were new diagnoses of osteoporosis in 5.8 percent of the women in the letrozole group and 4.5 percent of the women in the placebo group (P=0.07); the rates of fracture were similar. After the first interim analysis, the independent data and safety monitoring committee recommended termination of the trial and prompt communication of the results to the participants. CONCLUSIONS: As compared with placebo, letrozole therapy after the completion of standard tamoxifen treatment significantly improves disease-free survival.
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AET can cause side-effects such as hot flushes, joint pain and vulvovaginal symptoms.
“AET can cause side -effects such as hot flushes, joint pain and vulvovaginal symptoms. 5-7”
From A pilot randomised controlled trial of acceptance and commitment therapy for medication decision-making and quality of life in women with breast cancer: The ACTION trial (2024) · cites this paper as [6]
The Results and Table 5 report more hot flashes and arthralgia (joint pain) with letrozole than with placebo. They do not establish vulvovaginal symptoms as a letrozole side effect; the vaginal symptom reported, bleeding, was less frequent with letrozole. (LLM, conf=0.88)
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- Authors
- Goss, P. E., Ingle, J. N., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Tu, D., Shepherd, L. E., Pritchard, K. I., Livingston, R. B., Davidson, N. E., Norton, L., Perez, E. A., Abrams, J. S., Therasse, P., Palmer, M. J., & Pater, J. L.
- Affiliations
- Princess Margaret Cancer Centre (CA)
- Mayo Clinic (US)
- Inova Fairfax Hospital (US)
- Institut Jules Bordet (BE)
- International Breast Cancer Study Group (CH)
- Canadian Cancer Trials Group (CA)
- Sunnybrook Health Science Centre (CA)
- University of Washington (US)
- Johns Hopkins University (US)
- Memorial Sloan Kettering Cancer Center (US)
- National Cancer Institute (US)
- European Organisation for Research and Treatment of Cancer (BE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-11-06
- Volume
- 349
- Issue
- 19
- Pages
- 1793-1802
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2101881391
- Cited by
- 1,795
- References
- 44
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 22 · 2023: 26 · 2022: 34 · 2021: 30 · 2020: 40 · 2019: 31 · 2018: 37 · 2017: 57 · 2016: 61 · 2015: 78 · 2014: 51 · 2013: 80 · 2012: 66
- FWCI
- 72.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- National Institutes of Health (2u10ca038926-25)
- National Cancer Institute (CA-32102, (CA-25224, U10CA025224, U10CA032102, U10CA031946, CA 38926, U10CA021115, CA 21115, CA-31946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- letrozole, tamoxifen, aromatase inhibitors, early breast cancer, postmenopausal women, disease-free survival, overall survival, breast cancer recurrence, contralateral breast cancer, osteoporosis, adverse effects, hormone-dependent breast cancer
- MeSH terms
- Letrozole, Adult, Aged, Antineoplastic Agents, Breast Neoplasms, Double-Blind Method, Enzyme Inhibitors, Female, Humans, Middle Aged, Neoplasms, Hormone-Dependent, Nitriles, Quality of Life, Tamoxifen, Triazoles, Survival Analysis, Chemotherapy, Adjuvant, Postmenopause, Antineoplastic Agents, Hormonal, Aromatase Inhibitors
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