Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry

Abstract

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.

Fig. 1

Kaplan–Meier distant recurrence curves by Recurrence Score (RS) groups and clinicopathological characteristics. Rates of distant recurrence for the entire cohort (a) and by nodal status (b), age (c) tumor size (d), and tumor grade (e). For each RS category, the percentage of patients receiving chemotherapy is indicated. The box under each graph presents the number of patients at risk at each time point. Results for the subgroup analyses (b–e) should be interpreted cautiously due to small number of patients in some of the subgroups, low event rates, and the potential for selection bias with respect to the patients being RS tested

Fig. 2

Kaplan–Meier breast cancer death curves by Recurrence Score (RS) groups in all patients. The box under the curve presents the number of patients at risk at each time point

Fig. 3

Kaplan–Meier distant recurrence (a) and breast cancer death (b) curves in chemotherapy-untreated patients with Recurrence Score (RS) < 18 and RS 18–30 who received hormone therapy. The box under each graph presents the number of patients at risk at each time point

Fig. 4

Forest plots of 5-year distant recurrence risk (a) and 5-year breast cancer death (b) by adjuvant chemotherapy treatment