Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy

Abstract

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan–Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0–10, 17.8%; RS 11–25, 62.5%; RS 26–100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0–10, 11–25, and 26–100: 2.6% (95% confidence interval [CI], 1.1–6.2%), 6.1% (95% CI, 4.4–8.6%), and 13.1% (95% CI, 9.4–18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1–5.1%), 2.2% (95% CI, 1.3–3.7%), and 9.5% (95% CI, 6.0–14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0–10/11–25), 10-year distant recurrence and BCSM rates for RS 0–10 patients were 2.7% (95% CI, 1.1–6.5%) and 0.8% (95% CI, 0.1–5.3%), respectively, and for RS 11–25 patients, 5.7% (95% CI, 3.9–8.3%) and 2.0% (95% CI, 1.1–3.7%), respectively. For RS 11–25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0–25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26–100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

Personalised medicine and the decision to withhold chemotherapy in early breast cancer with intermediate risk of recurrence – a systematic review and meta-analysis

“… Stemmer et al 2017 [ 40 ] Israel Cohort 637 I = 508 C = 129 Oncotype DX Recurrence RS ≤ 25 DR at 5 yrs: 21/488 (4.4%) vs 2/89 (2.3%); P = 0.521 Node+. Unmatched groups Characteristics of compared groups not reported + – – Stemmer et al 2019 [ 39 ] Israel Cohort 853 I = 773 C = 80 Oncotype DX Recurrence RS 11-25 DR at a median follow-up of 9 years: 34/773 (4.4%) vs 6/80 (10%) (P = 0.703) Unmatched groups Characteristics of compared groups not reported ? – – Wen et al 2016 [ 42 ] USA Cohort 1,406 I = 1,236 C = 170 Oncotype DX Recurrence RS < 18 DR at a median follow-up of 46 months: 5/1,236 (0.4%) vs 1/170 (0.6%) Unmatched groups Characteristics of compared groups not reported + – – *We inverted the HR provided in the publication if their analysis presented results for control versus intervention; 95% CI provided within parentheses.…”

The Potential Use of Tumour-Based Prognostic and Predictive Tools in Older Women with Primary Breast Cancer: A Narrative Review

“…Oncotype DX stands out as the only tool validated for both predictive and prognostic utility. It is the most used tool in the USA and has the largest body of evidence in terms of trials conducted and research undertaken [ 13 , 66 ]. The large-scale TAILORx study [ 36 ] was promising in its recruitment of older women, but in the intermediate-risk group the study focused on, only 4.3% of the women were over 70 years old.…”

“…Patients who have been identified as ‘low risk’ of recurrence by tools of this kind have been shown to have a very low risk of metastatic disease after extensive follow-up. A study by Stemmer et al [ 13 ] examined 1365 women from the Clalit Health Services Registry with node-negative, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who underwent Oncotype DX testing between the years 2006 and 2009. The median age of the group was 60 years (standard deviation 52–66 years).…”

Ethnicity, recurrence score distribution, and clinical outcomes in ER + HER2‐negative breast cancer patients in Israel: A registry analysis

“…The only statistically significant differences in baseline patient/tumor characteristics were age and tumor size (younger patients and a higher proportion of larger tumors in Arabs/Druze vs Jewish patients; Supplementary Table 1). A second RS distribution analysis involved a subset of the first cohort for which treatments and 10‐year clinical outcomes were previously reported 2 . In this cohort (n = 1365, all node‐negative; 93% Jews, 7% Arabs/Druze), RS distribution was also similar between the ethnic groups ( P = .75), and the only statistically significant difference was age (Arabs/Druze patients were younger compared to the Jewish patients; Supplementary Table 2).…”

“…Kaplan–Meier curves for distant recurrence and BCSM by ethnicity and RS category in the Stemmer et al cohort 2 (n = 1365). In the Arabs/Druze group, there were 3 cases of distant recurrence (1 in RS 11‐25 patients and 2 in RS 26‐100 patients), and all 3 died.…”