Is oestrogen receptor-negative/progesterone receptor-positive (ER-/PR+) a real pathological entity?

Background: The existence of oestrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) breast cancer continues to be an area of controversy amongst oncologists and pathologists.

Methods: To re-evaluate breast cancers originally classified as ER-/PR+ via Oncotype DX® assay and compare molecular phenotype with Recurrence Score® (RS) result, clinicopathologic features and clinical outcomes were retrospectively obtained from electronic health records between January 1998 and June 2005. Archived formalin-fixed, paraffin-embedded (FFPE) tumour specimens were tested for the expression of ER, PR and human-epidermal-growth-factor-2. The number of positive ER-/PR+ samples confirmed by transcriptional analysis was the primary outcome of interest with event-free and overall survival as secondary outcomes. Biopsies from 26 patients underwent Oncotype DX testing and analysis.

Results: Approximately 60% were middle-aged (40-50 years old) women, and 84.6% had invasive ductal carcinoma. Based on the Oncotype DX assay, approximately 65% ( = 17) had ER+/PR+ status; 23% (N = 6) had ER-/PR- status; and 12% had a single hormone positive receptor (1 ER-/PR+, 2 ER+/PR-) status. Almost one-quarter of patients were stratified into the low-RS (<18) or intermediate-RS (18-30) results, and half of the patients had a high-RS (>30) result.

Conclusion: Our findings suggest the ER-/PR+ subtype is not a reproducible entity and emphasises the value of retesting this subtype via molecular methods for appropriate treatment selection and patient outcomes. Multigene assay analysis may serve as a second-line or confirming tool for clinical determination of ER/PR phenotype in breast cancer patients for targeted therapies.