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.