21-Gene Assay and Breast Cancer Mortality in Ductal Carcinoma in Situ.

BACKGROUND The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the over-treatment of DCIS. The 21-gene Recurrence Score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown. METHODS We performed a population-based analysis of 1,362 individuals of DCIS aged ≤75 years at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as > 25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were two-sided. RESULTS With 16 years median follow-up, 36 (2.6%) died of BC and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (HR = 11.27 95%CI = 3.00 to 42.33, p<.001 in women ≤50 years of age at diagnosis treated with BCS alone, culminating in a 9.4% (95%CI= 2.3 to 22.5) 20-year risk of BC death. For women with a high RS, treatment with RT was associated with a 71% (HR = 0.29, 95%CI = 0.10 to 0.89. p = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC. CONCLUSION The 21-gene RS predicts BC mortality in DCIS and combined with age (≤50 years) at diagnosis can identify individuals for whom RT reduces the risk of death from BC.