Comparative Analysis of Oncotype DX Recurrence Scores in Screen‑Detected Versus Symptomatic Early‑Stage Breast Cancer: The COSSEB Study

TL;DR

This study compares genomic risk scores in breast cancers detected through screening versus those found due to symptoms, finding similar risk levels and treatment recommendations.

Contribution

The study provides new evidence that genomic risk scores are comparable between screen-detected and symptomatic early breast cancers.

Findings

Screen-detected cancers were smaller and more likely to use breast-conserving surgery.

Low HER2 expression was more common in screen-detected cancers.

Genomic risk scores and chemotherapy recommendations were similar between the two groups.

Abstract

Background: Breast cancers detected through population-based screening mammography (screen-detected breast cancers, SDBCs) typically differ from cancers first identified after symptom onset (symptomatic breast cancers, SBCs) in stage and biology. We investigated whether these clinical differences extend to genomic risk as measured by the 21-gene Oncotype DX Recurrence score (ODX-RS), which guides adjuvant treatment in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer, and examined whether presentation mode influenced adjuvant treatment recommendations.

Methods: We performed a retrospective analysis of 200 women aged ≥50 years who underwent surgery for ER-positive, HER2-negative early breast cancer between 2017 and 2025. The cohort comprised 100 SDBCs and 100 age-matched SBCs, all of whom had low-burden axillary disease and successful ODX-RS testing. Clinicopathologic features, ODX-RS categories (≤25 vs ≥26), and adjuvant treatment recommendations were compared between groups using counts/percentages (or differences for continuous variables) with two-tailed P values; adjusted associations, where applicable, are reported as odds ratios (ORs) with 95% confidence intervals.

Results: SDBCs were smaller (median 24 mm vs 28 mm; median difference −4 mm (95% CI −7 to −0.5); P=0.05) and more frequently treated with breast-conserving surgery (77% vs 61%; P=0.01). Low HER2 expression (immunohistochemistry 1+) was more common in SDBCs (54% vs 38%; P=0.014). An ODX-RS ≥26 occurred slightly more often in SBCs than SDBCs (21% vs 17%; P=0.47), and subgroup analyses by tumor size and grade showed largely similar score distributions between groups. Adjuvant chemotherapy was recommended for 23% of SBCs and 19% of SDBC cases (P=0.49); endocrine therapy was advised for most patients in both cohorts.

Conclusions: Screen-detected and symptomatic ER-positive/HER2-negative early breast cancers exhibited broadly comparable ODX-RS distributions. Mode of presentation alone should therefore not dictate adjuvant chemotherapy decisions; multigene testing and standard clinicopathologic factors remain essential for individualized treatment planning. Larger, prospective studies are warranted to validate and extend these observations.

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