Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study

Abstract

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40-84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N=38,568). Unadjusted 5-year BCSM were 0.4% (n=21,023; 95% confidence interval (CI), 0.3-0.6%), 1.4% (n=14,494; 95% CI, 1.1-1.7%), and 4.4% (n=3,051; 95% CI, 3.4-5.6%) for Recurrence Score <18, 18-30, and ⩾31 groups, respectively (P<0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P<0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N=4,691), 5-year BCSM (unadjusted) was 1.0% (n=2,694; 95% CI, 0.5-2.0%), 2.3% (n=1,669; 95% CI, 1.3-4.1%), and 14.3% (n=328; 95% CI, 8.4-23.8%) for Recurrence Score <18, 18-30, ⩾31 groups, respectively (P<0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials.

Figure 1

Five-year estimates of breast-cancer-specific mortality, by Recurrence Score group (prespecified primary analysis). Patients with HR+, HER2-negative, node-negative breast cancer who had Recurrence Score (RS) results <18 (green), 18–30 (yellow), or ⩾31 (red) were included in the primary analysis. Five-year estimates of breast-cancer-specific mortality (BCSM) with 95% CIs (green, yellow, and red shading) were 0.4% (0.3–0.6%) in the RS <18 group, 1.4% (1.1–1.7%) in the RS 18–30 group, and 4.4% (3.4–5.6%) in the RS ⩾31 group. Five-year estimates of BCSM±s.e. are shown to the right of their respective lines. Numbers of patients at risk in each group are shown beneath the graph.

Figure 2

Five-year estimates of breast cancer-specific mortality, by Recurrence Score group (subgroup analyses). Patients with HR+, HER2-positive, node-negative (a,c,e,g,i) and node-positive (micrometastases up to three positive nodes; b,d,f,h,j) breast cancer who had Recurrence Score (RS) results <18 (green), 18–30 (yellow), or ⩾31 (red) were included in subgroup analyses by age (a,b), race (c,d), socioeconomic status (e,f) as defined by the Yost composite index, tumor grade (g,h), and tumor size (i,j). Five-year estimates of breast-cancer-specific mortality (BCSM)±s.e. are shown. Percentages of patients with chemotherapy use reported as ‘yes’ as a proportion of all patients (‘yes’ or ‘no/unknown’ chemotherapy use) are shown beneath the graph.

Figure 2

Five-year estimates of breast cancer-specific mortality, by Recurrence Score group (subgroup analyses). Patients with HR+, HER2-positive, node-negative (a,c,e,g,i) and node-positive (micrometastases up to three positive nodes; b,d,f,h,j) breast cancer who had Recurrence Score (RS) results <18 (green), 18–30 (yellow), or ⩾31 (red) were included in subgroup analyses by age (a,b), race (c,d), socioeconomic status (e,f) as defined by the Yost composite index, tumor grade (g,h), and tumor size (i,j). Five-year estimates of breast-cancer-specific mortality (BCSM)±s.e. are shown. Percentages of patients with chemotherapy use reported as ‘yes’ as a proportion of all patients (‘yes’ or ‘no/unknown’ chemotherapy use) are shown beneath the graph.