ArticlesAssessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up
Introduction
Aromatase inhibitors are now part of standard treatment for most postmenopausal women with oestrogen-receptor-positive and/or progesterone-receptor-positive early invasive breast cancer.1 Generally, these agents, such as letrozole, are given either alone, or in sequence, before or after tamoxifen. The BIG 1-98 trial's design allowed the comparison between tamoxifen and letrozole monotherapies, and the comparison of the sequential treatments with monotherapy.2, 3, 4, 5 The population included has a persistent, long-term risk of breast-cancer recurrence requiring extended follow-up.6, 7 The trial was therefore designed to include updates every 2 years of the primary analyses to monitor long-term safety and efficacy. We present updated results at a median follow-up of 8·1 years (range 0–12·4), 12 years since entry of the first patient, to provide a comparison of 5 years of letrozole versus tamoxifen monotherapy, and a direct comparison of each sequential treatment with letrozole monotherapy.
Section snippets
Study design
BIG 1-98 is a randomised, phase 3, double-blind trial that recruited postmenopausal women with early breast cancer positive for oestrogen receptor or progesterone receptor, or both.2, 3, 4, 5 Primary surgery with resulting clear margins and adequate haematological, renal, and hepatic function were required. Exclusion criteria included evidence of metastatic disease and previous or concurrent cancer other than adequately treated non-invasive breast or cervical cancer, or basal-cell or
Results
Among all 8010 patients, 2074 disease-free survival events and 1284 deaths were noted at this protocol-specified update, 12 years since trial commencement and after a median follow-up time of 8·1 years (range 0–12·4). This compares with 1569 events and 923 deaths noted at the previous 10-year update.4 The additional 505 disease-free survival events, which were mostly recorded between 5 and 11 years from randomisation, included 279 (55%) breast cancer recurrences, 106 (21%) second non-breast
Discussion
Although it has been 12 years since BIG 1-98 opened for accrual, disease-free survival events continue to occur in large numbers in this population of postmenopausal women with endocrine-responsive early breast cancer. The trial protocol specified that updates of the primary analyses would be done every 2 years in recognition of the prolonged, persistent hazard of breast-cancer recurrence in this population.6 At this update, 2074 disease-free survival events were recorded in all 8010 patients,
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Members of the BIG 1-98 Collaborative Group and IBCSG are listed in the webappendix (pp 2–7)