ArticlesTreatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials
Introduction
In 1982, the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated the first randomised clinical trial (B-14) designed to assess the efficacy of adjuvant tamoxifen treatment in women with oestrogen-receptor-positive breast cancer and histologically negative axillary lymph nodes. Initial results from that study, from nearly 3000 women, showed that tamoxifen-treated women had a significantly better outcome than did those who received placebo.1 Findings from long-term follow-up continued to lend support to the initial results.2, 3, 4 Before the B-14 results became available, we thought that the degree of benefit achieved with tamoxifen would probably be insufficient to eliminate the need to assess potentially more effective therapeutic regimens in that patient population. Consequently, in 1988, we implemented B-20, a randomised trial designed to test the hypothesis that addition of chemotherapeutic drugs to tamoxifen would result in a greater benefit than that achieved with tamoxifen alone. Findings from more than 2000 women enrolled in the B-20 study showed a significantly better outcome after treatment with chemotherapy and tamoxifen.5
In this report, we present data on recurrence-free survival and overall survival of all women in the B-14 study through 15 years of follow-up, and of all women in the B-20 study through 12 years of follow-up. We also present information about the outcome of women in both studies according to age, menopausal status, and concentrations of tumour oestrogen receptors, and estimate the extent of the progress achieved in the treatment of node-negative patients with oestrogen-receptor-positive tumours.
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Patients
Women at NSABP institutions in the USA and Canada who had primary breast cancer and axillary lymph nodes that were negative for cancer on histological examination, were eligible for participation in either the B-14 or the B-20 trial if their tumours were oestrogen-receptor-positive—ie, had 10 or more fmol per mg cytosol protein—and if they fulfilled specific eligibility criteria that were similar in both trials. Written, informed consent was required from patients who entered the study. Both
B-14
On average, women had significantly better outcomes after tamoxifen treatment than after placebo throughout 15 years of follow-up (recurrence-free survival 78% vs 65%, p<0·0001; overall survival 71% vs 65%, p=0·0008, figure 2). When these outcomes were examined in women according to age (table 1), a significant benefit of tamoxifen in women aged 49 years or younger was noted for each of the endpoints. In women aged 50–59 years, a significant benefit of tamoxifen was apparent for recurrence-free
Discussion
In the B-14 study, the benefit from tamoxifen initially reported after 4 years of follow-up1 has continued to increase through 15 years for all patients, irrespective of age. Moreover, the B-14 study has provided the longest prospective natural history information from oestrogen-receptor-positive, node-negative breast cancer patients treated with surgery alone. The rate of nearly 35% for treatment failure and about 35% for overall mortality in women who were assigned to placebo emphasises the
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