Abstract

BackgroundThe existence of oestrogen receptor-negative (ER−)/progesterone receptor-positive (PR+) breast cancer continues to be an area of controversy amongst oncologists and pathologists.MethodsTo 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.ResultsApproximately 60% were middle-aged (40–50 years old) women, and 84.6% had invasive ductal carcinoma. Based on the Oncotype DX assay, approximately 65% (N = 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.ConclusionOur 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.

Highlights

  • Breast cancer is not one disease but comprises a heterogeneous disease group of a growing number of biological subtypes that have diverse natural histories and responsivenessPublished: 24/08/2021 Received: 01/07/2021Publication costs for this article were supported by ecancer (UK Charity number 1176307).Copyright: © the authors; licensee ecancermedicalscience

  • Of the hormone receptors (HRs), ER expression is predictive in identifying tumours that will respond to endocrine therapy, whereas progesterone receptors (PR) expression is prognostic with patients exhibiting PR− breast cancers having poor outcomes [2,3,4]

  • By re-examining the phenotype and associated patient outcomes of breast cancer biopsies previously designated as ER−/PR+ with updated techniques, our results suggest that ER−/PR+ tumours are not a reproducible pathological entity, though small sample size precludes definitive conclusions regarding the existence or non-existence of this subtype

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Summary

Introduction

Determination of appropriate breast cancer treatments and prognostic outcomes are dependent on the accurate histologic classification and measurement of two main biomarker groups: hormone receptors (HRs; including oestrogen (ER) and progesterone receptors (PR)) and human epidermal growth factor 2 (HER2) [1]. Endocrine therapy is considered the most effective treatment to downregulate ER-related cancer cell functions with relatively low toxicity compared to cytotoxic chemotherapy in patients with ER+ breast cancer [1]. The existence of oestrogen receptor-negative (ER−)/progesterone receptor-positive (PR+) breast cancer continues to be an area of controversy amongst oncologists and pathologists

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