SAN ANTONIO -- Adjuvant therapy for excised ductal carcinoma in situ (DCIS) significantly reduced the risk of breast cancer recurrence, but radiotherapy and tamoxifen affected recurrence patterns differently, according to long-term data from a large, randomized clinical trial.
Radiotherapy reduced the risk of ipsilateral recurrence by 68% during almost 13 years of follow-up but had no effect on contralateral recurrence. The benefit emerged early in the course of follow-up.
Tamoxifen had a smaller overall effect but reduced the risk of ipsilateral and contralateral recurrence. Tamoxifen's benefit also required more time to emerge.
"This updated analysis confirms the benefit of radiotherapy for the treatment of DCIS," Jack Cuzick, MD, of Cancer Research UK in London, said at the San Antonio Breast Cancer Symposium. "The benefits are confined to the ipsilateral breast."
"Tamoxifen significantly reduced all ipsilateral and contralateral recurrences," he added. "The effect was larger for contralateral tumors and for low- to intermediate-grade tumors. Tamoxifen had minimal effect on invasive ipsilateral recurrence."
The findings came from a randomized clinical trial begun in 1990 by investigators in England, Australia, and New Zealand. The primary objective was to determine the value of treating surgically excised DCIS adjuvantly with radiation or tamoxifen to reduce the risk of recurrence.
The initial report from the study showed that radiation therapy reduced the risk of recurrence by more than 50% (Lancet 2003; 362: 95-102). However, adjuvant tamoxifen was associated with a nonsignificant 17% reduction in recurrence risk.
The initial report came after a median follow-up of 52 months. Cuzick presented data on patients who had a median follow-up of 12.7 years.
The trial involved 1,701 patients with completely excised DCIS. They were randomized to no adjuvant treatment, adjuvant tamoxifen, adjuvant radiotherapy, or adjuvant treatment with both therapies. Either adjuvant therapy could be omitted at the physician's discretion. A total of 1,576 patients received tamoxifen, and 1,030 received radiotherapy.
Comparing all patients who received radiation therapy with those who received none, investigators found that the magnitude of radiotherapy's benefit on ipsilateral recurrence increased from an absolute difference of 8.6 percentage points at five years (4.4% versus 13% for patients who received no radiation therapy) to 14.6 percentage points at 15 years (7.1% vs 21.7%).
The difference in ipsilateral recurrence translated into a hazard ratio of 0.32 (P<0.0001) and did not differ substantially for invasive recurrence (HR 0.32) versus DCIS recurrence (HR 0.38).
Radiotherapy had a much smaller impact on contralateral recurrence, 3.4% versus 4.1%, representing a nonsignificant 16% risk reduction.
Considering all recurrences, irrespective of site or type, radiation therapy reduced the risk of recurrence by almost 60% (HR 0.41, 95% CI 0.30 to 0.56).
The benefits of tamoxifen also continued to accrue over time, such that the overall risk reduction reached 29% and achieved statistical significance (HR 0.71, 95% CI 0.58 to 0.88, P=0.002).
The absolute benefit increased from 3.3 percentage points after five years of follow-up (13.3% with tamoxifen versus 16.6 points without) to 6.3 percentage points at 10 years (18.1% versus 24.4%) to 6.5 points at 15 years (19.6% versus 26.1%).
Tamoxifen reduced the risk of ipsilateral recurrence by 22% (HR 0.78, 95% CI 0.62 to 0.99) The effect on invasive recurrences was negligible (HR 0.95) but significant for recurrent DCIS (HR 0.70, 95% CI 0.51 to 0.86).
Contralateral recurrences were reduced by 56% with tamoxifen (HR 0.44, 95% CI 0.25 to 0.77), including a 53% reduced risk of invasive recurrence (95% CI 0.24 to 0.94) and a 64% reduction in DCIS recurrence (95% CI 0.11 to 1.12).
The 29% overall risk reduction with tamoxifen included a 19% lower incidence of invasive recurrence (HR 0.81, 95% CI 0.59 to 1.12) and a 33% lower incidence of recurrent DCIS (HR 0.67, 95% CI 0.50 to 0.90).
Overall mortality was 10.6%, including 9.6% among patients who received neither adjuvant therapy, 9.7% in patients treated with radiation therapy alone, and 10.2% in patients treated with tamoxifen alone.
Patients who received both therapies had the highest mortality (13.6%), although Cuzick said the between-group differences were not statistically significant.
Cuzick had no relevant disclosures to report.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
San Antonio Breast Cancer SymposiumSource Reference: Cuzick J, et al "Beneficial effect of tamoxifen for women with DCIS: Long-term benefits from the UK/ANZ DCIS trial in women with locally excised DCIS" SABCS 2009; Abstract 34.