Beneficial Effect of Tamoxifen for Women with DCIS: Long-Term Results from the UK/ANZ DCIS Trial in Women with Locally Excised DCIS.

Abstract

Abstract Background: Initial results of the UK/ANZ DCIS trial found that adjuvant radiotherapy reduced the recurrence of ipsilateral invasive breast cancer (BC) and ductal carcinoma in situ (DCIS) by 55% and 64% respectively, but the effect of tamoxifen was smaller (Lancet 2003, 362: 95-102). Here, we report an updated analysis of this trial.Methods: 1701 women with completely locally excised DCIS were enrolled in a randomised 2x2 trial of radiotherapy, tamoxifen or both. Elective decision to withhold or provide one of the treatments was also permitted and long-term follow-up was performed by treating hospitals. Seven patients were excluded due to protocol violations leaving 1694 patients available for analysis.Results: After a median follow-up of 12.7 years, a total of 376 breast cancers were diagnosed; 162 invasive (122 ipsilateral; 39 contralateral) and 197 DCIS (173 ipsilateral; 17 contralateral). Radiotherapy continued to reduce the incidence of ipsilateral invasive disease (HR=0.32 (0.19-0.56), P<0.0001) and ipsilateral DCIS (HR=0.38 (0.22-0.63), P<0.0001), but had no significant effect on contralateral breast cancer (HR=0.84 (0.45-1.58)). Tamoxifen significantly reduced all recurrences by 29% (HR=0.71 (0.58-0.88), P=0.002) (Figure 1). This consisted of a 30% (HR=0.70 (0.51-0.86)) reduction in recurrent ipsilateral DCIS, a small 5% (HR=0.95 (0.66-1.38)) reduction in ipsilateral invasive disease, and a 56% (HR=0.44 (0.25-0.77)) reduction in contralateral tumours. Overall, women randomised to radiotherapy and not receiving tamoxifen had a 59% reduction in recurrence (HR=0.41 (0.30-0.57), P<0.0001), whereas those randomised to tamoxifen and not receiving radiotherapy had an overall reduction of 29% (HR=0.71 (0.57-0.87), P=0.001).Conclusion: This updated analysis confirms the long-term benefit of radiotherapy in women with DCIS treated by complete local excision and also established a benefit for tamoxifen. Ongoing work will examine in detail which subsets of tumours (e.g. high grade, oestrogen receptor positive) will benefit most from these treatments. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 34.