Women with ductal carcinoma insitu (DCIS) are significantly less likely to develop subsequent ipsilateral DCIS or invasive disease if they are given radiotherapy, reports the 12.7 year follow-up of the UK/ANZ DCIS study. In the 4.4 year follow-up no significant reductions were found in new breast events for women given tamoxifen, however with longer term follow up tamoxifen was shown to reduce the incidence of recurrent ipsilateral DCIS and contralateral tumours.

Ductal carcinoma in situ (DCIS), or cancer in the milk ducts of the breast, represents 10% of all breast carcinomas and around 20% of screen-detected cancers. The UK, Australia and New Zealand (UK/ANZ) DCIS trial, which started shortly after the British Breast Cancer screening programme got underway in 1990, was designed to establish whether additional treatment with tamoxifen or radiotherapy, or both tamoxifen and radiotherapy would reduce the likelihood of cancer coming back following surgery to completely remove DCIS.

Initial results published in 2003, after a median follow-up of 4.4 years, suggested that radiotherapy reduced new breast events of ipsilateral invasive and DCIS compared with no radiotherapy, but that no significant events were noted with tamoxifen.

In the current study, Jack Cuzick and colleagues from Cancer Research UK report the long term follow-up(median 12.7 years) of women from the UK/ANZ DCIS trial. Between May 1990 and August 1998, 912 women were randomly assigned in a two by two factorial design to radiotherapy and tamoxifen (n=242), radiotherapy alone (n=224) , tamoxifen alone (n=220) or to no adjuvant treatment (n=226).

Results at a median follow-up of 12.7 years showed:

- Radiotherapy after surgery reduced the risk of ipsilateral invasive disease by 68% and the risk of ipsilateral DCIS by 62% (both P<0.0001); but had no effect on contralateral breast cancer (p=0.6). This corresponds to an absolute 10-year reduction in local cancer recurrences of 12.6%.

- Tamoxifen reduced recurrent ipsilateral DCIS by 40% (p=0.03), and contralateral tumours by 56% (p=0.005). However, tamoxifen had no effect on ipsilateral invasive breast cancer, and seemed deliver no added benefit in patients who were given radiotherapy.

- Adverse events were not recorded, although there was a small statistically significant increase in the risk of cardiovascular death in patients who received radiotherapy.

"This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision," write the authors.

In an accompanying editorial Henry Kuerer, from University of Texas MD Anderson Cancer Center (Houston, Texas), expressed concerns that we are over treating many cases of small, mammographically detected DCIS. "For patients with small (<1cm) completely excised low-grade and intermediate-grade lesions, the best course might be to monitor for recurrence and offer adjuvant treatment only as needed," he wrote, adding that the focus should now be on accurate molecular identification of patients with DCIS who can safely forego therapy because the risk of developing life-threatening invasive carcinoma is so low.

Reference

J Cuzick, I Sestak, S Pinder et al Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long term results from the UK/ANZ DCIS Trial Lancet Oncology DOI: 10.1016/S1470-2045(10)70266-7