Abstract
To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients. The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters. PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ(2) 15.32, P < 0.001; ROR-based risk groups: ΔLRχ(2) 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease. PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors.
Highlights
More than two-thirds of breast cancers express estrogen receptor (ER) and/or progesterone receptor (PgR; ref. 1).These patients are candidates for treatment with drugs targeting ER signaling either by interfering with ligand binding, blockade of estrogen biosynthesis, or ER downregulation
Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group
The distant recurrence-free survival (DRFS) differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease
Summary
More than two-thirds of breast cancers express estrogen receptor (ER) and/or progesterone receptor These patients are candidates for treatment with drugs targeting ER signaling either by interfering with ligand binding (tamoxifen), blockade of estrogen biosynthesis (aromatase inhibitors or gonadotropin-releasing hormone analogs), or ER downregulation (fulvestrant). Adjuvant treatment with tamoxifen reduces the risk-of-recurrence (ROR) in patients with ER-positive breast cancer over all time periods by 39% [1]. 50% of recurrences in ER-positive disease will occur after the first 5 years beyond initial diagnosis and tamoxifen treatment [1]. Mortality and recurrence risk vary over time according to molecular and clinical risk factors. In contrast with ERnegative tumors, which usually develop metastases early (mostly within 5 years) after initial diagnosis and treatment, the annual recurrence rates of ER-positive breast cancers are
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