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.

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

“…The identification of patients with high clinical risk and low genomic score with at least a 92.5% chance of being free of distant metastasis without chemotherapy at 5 years was demonstrated using the Mammaprint assay in the MINDACT trial . Prospective outcomes in >60,000 patients (including both clinical and epidemiological data) treated based on 21‐gene assay results have shown that patients within the low RS group (RS < 18) have excellent outcomes without chemotherapy . The prognostic power of the RS was validated in an endocrine‐treated NSABP B14 cohort, in the Kaiser Permanante, JBCRG, SWOG 8814 and in the transATAC studies .…”

“…21 Prospective outcomes in >60,000 patients (including both clinical and epidemiological data) treated based on 21-gene assay results have shown that patients within the low RS group (RS < 18) have excellent outcomes without chemotherapy. [32][33][34][35][36][37][38] The prognostic power of the RS was validated in an endocrine-treated NSABP B14 cohort, in the Kaiser Permanante, JBCRG, SWOG 8814 and in the trans-ATAC studies. 2,9,11,23,24,39 The predictive power of RS for the prediction of chemotherapy benefit was initially validated in the NSABP B20 study in endocrine only vs. chemoendocrinetreated cohorts.…”

Lymph node involvement: Positive about the role of the recurrence score in estrogen‐driven breast cancer?

“…In a different nonrandomized study of 709 patients who had pN1 lymph node status with micrometastases (pN1mic) (n = 298) or pN1 breast cancer from the Israeli Clalit Health Services registry, chemotherapy was associated with a lower Cancer January 15, 2019 distant recurrence rate in those who had a RS from 18 to 30 (1.0% vs 9.7%; P = .02). 13 This chemotherapy benefit was not observed for those who had a RS <18 (n = 379), although only 27 patients (7%) received chemotherapy in that group. Although data from those nonrandomized studies should be interpreted with caution, they also support the idea that the RS may identify a subgroup of patients with lymph node-positive breast cancer for whom chemotherapy is not warranted.…”

“…In multivariable analysis, the number of positive lymph nodes and RS category were independent predictors of breast cancer‐specific survival. In a different nonrandomized study of 709 patients who had pN1 lymph node status with micrometastases (pN1mic) (n = 298) or pN1 breast cancer from the Israeli Clalit Health Services registry, chemotherapy was associated with a lower distant recurrence rate in those who had a RS from 18 to 30 (1.0% vs 9.7%; P = .02) . This chemotherapy benefit was not observed for those who had a RS <18 (n = 379), although only 27 patients (7%) received chemotherapy in that group.…”

Routine Use of Oncotype DX Recurrence Score Testing in Node-Positive Hormone Receptor-Positive HER2-Negative Breast Cancer: The Time Has Come

“…However, discordance between clinical risk defined by tumor grade and genomic risk defined by RS has been demonstrated in up to 30% of patients in other datasets of both node-negative and node-positive patients, highlighting the potential for genomic assays to refine prognosis beyond traditional clinicopathologic factors. [4][5][6] After a median follow-up of 57 months, there were significant differences among RS risk groups with respect to breast cancer-specific survival (BCSS) and overall survival (OS). Multivariate analysis showed that both RS risk group and the AJCC pathologic prognostic stage were independent prognostic factors for BCSS and OS.…”