Prognostic Impact of the 21-Gene Recurrence Score Assay Among Young Women With Node-Negative and Node-Positive ER-Positive/HER2-Negative Breast Cancer

Abstract

PURPOSE The 21-gene recurrence score (RS) assay is prognostic among women with early-stage estrogen receptor–positive (ER+) and human epidermal growth factor receptor 2–negative (HER2−) breast cancer and is used to inform recommendations for chemotherapy. Women ≤ 40 years of age represent a minority of patients studied using gene expression profiles. METHODS The Young Women's Breast Cancer Study is a prospective cohort of women diagnosed with breast cancer at age ≤ 40 years and enrolled patients between 2006 and 2016 (N = 1,302). We identified patients with stage I-III ER+/HER2− breast cancer. The RS assay was performed on banked specimens for patients who had not been tested clinically. Distant recurrence-free survival (DRFS) was assessed by TAILORx and traditional RS risk groups among patients with axillary node–negative (N0) and limited node–positive (N1) breast cancer. RESULTS Among eligible women (N = 577), 189 (33%) had undergone RS testing, and 320 (56%) had banked specimens sufficient for testing. Median follow-up was 6.0 years. Median age at diagnosis was 37.2 years; 300 of 509 patients (59%) had N0 breast cancer, of whom 195 (65%) had an RS of 11-25 and fewer than half (86 of 195; 44%) received chemotherapy. Six-year DRFS rates were 94.4% and 92.3% (RS < 11), 96.9% and 85.2% (RS 11-25), and 85.1% and 71.3% (RS ≥ 26) among women with N0 and N1 disease, respectively. CONCLUSION The RS assay is prognostic among young women with node-negative and limited node-positive breast cancer, representing a valuable tool for risk stratification. Disease outcomes with a median follow-up of 6 years among young women with N0 disease and an RS of 0-25, a minority of whom received chemotherapy, and node-positive disease with an RS < 11 were very good, whereas those with N0 disease and an RS ≥ 26 or N1 disease with an RS ≥ 11 experienced substantial risk of early distant recurrence.

Clinical utility of genomic signatures in young breast cancer patients: a systematic review

“…Only three studies compared the indication to perform genomic tests across age groups, all of which focused on the impact of age on Oncotype DX testing in the United States [20][21][22] . Overall, there was a tendency toward higher testing probability in younger patients (32 vs. 29%, p = 0.033) ( Fig.…”

“…Prognostic value of genomic signatures in YWBC and potential impact of chemotherapy use A total of nine studies evaluated the prognostic performance of genomic signatures in young women (using a per-study definition) and disclosed survival outcomes according to age group (Table 2). However, only two studies included in this review performed a dedicated analysis on the prognostic value of genomic signatures in women aged ≤40 years at diagnosis, both using Oncotype DX 21,23 .…”

“…Other noteworthy analyses of prognostic value of Oncotype DX in YWBC include Harbeck et al 24 who demonstrated that patients aged <40 years with a high recurrence score using the TAILORx threshold (i.e., >25) had a similar DFS than their older counterparts when treated with chemotherapy, and Sparano et al 25 who showed that patients aged ≤40 years who had high-intermediate risk scores (i.e., [16][17][18][19][20][21][22][23][24][25] did not benefit from chemotherapy addition in terms of DFS.…”

“…3 Proportion of patients that underwent genomic testing with Oncotype DX according to age. Data were extracted from studies by Poorvu et al 21 , Lund et al 20 , and Williams et al 22 . Table 2.…”

“…Table 2. Studies investigating the impact of genomic test risk score and outcomes in young breast cancer patients 21,23,25,27,29,32,[48][49][50] . Only those with a high ESR1 expression were taken into account.…”