Adjuvant tamoxifen over drie decennia: effect op borstkankervrije en afstandsrecidiefvrije overleving

AIMS: The primary aim was to compare 2 years of adjuvant tamoxifen versus no systemic treatment in premenopausal patients with oestrogen receptor (ER)-positive tumours, regarding breast cancer-free interval (BCFi) and distant recurrence-free interval (D-RFi), with 30 years of follow-up and for specified intervals. Moreover, we aimed to investigate the effects of adjuvant tamoxifen on the incidence of secondary malignancies and survival after distant recurrence. METHODS: Premenopausal patients with primary breast cancer were randomised to 2 years of tamoxifen (n = 277) or no systemic treatment (n = 287), irrespective of ER status. Information regarding events was collected by a review of medical records and from national registers. RESULTS: The median follow-up for all patients without events was 28 years, and only four of the patients alive had a follow-up of <20 years. With 30 years of follow-up, tamoxifen prolonged BCFi in the intention-to-treat population (hazard ratio [HR] = 0.76, 95% confidence interval (CI) 0.61-0.94, p = 0.011) compared with no treatment. In patients with ER-positive tumours (n = 362), tamoxifen prolonged BCFi (HR = 0.62, 95% CI 0.47-0.82, p = 0.001) and D-RFi (HR = 0.73, 95% CI 0.54-0.99, p = 0.043). The positive effect on BCFi was significant also for the interval >15-30 years (HR = 0.53, 95% CI 0.28-0.98, p = 0.042). For patients with ER-positive tumours who were diagnosed with distant recurrence (n = 165), survival after distant recurrence was shorter among tamoxifen-treated patients (median, 29 months versus 43 months). The incidence of contralateral breast cancer was 42% lower in the tamoxifen group (HR = 0.58, 95% CI 0.35-0.96, p = 0.035), whereas no differences were observed regarding other secondary malignancies. CONCLUSIONS: With three decades of follow-up, 2 years of adjuvant tamoxifen reduced the incidence of breast cancer-related events and distant recurrence, and the carryover effect seems to extend beyond 15 years. Moreover, adjuvant tamoxifen seems to be associated with shorter survival after diagnosis of distant recurrence.