Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER−/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER−/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER−/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER−/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER−/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER−/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER−/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER−/PR- None of the cases were confirmed to be ER−/PR+. The ER−/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.