The combined endocrine receptor in breast cancer, a novel approach to traditional hormone receptor interpretation and a better discriminator of outcome than ER and PR alone

Background: The functional role of progesterone receptor (PR) signalling was previously unclear and PR testing in breast cancer is controversial. Recent defining work has highlighted the functional crosstalk that exists between the oestrogen receptor (ER) and PR. The purpose of this retrospective cohort study was to compare the prognostic value of the combined ER and PR score with either ER or PR alone.

Methods: Tumour Allred ER and PR scores were reclassified as negative, low and high. The combined endocrine receptor (CER) was calculated as the average of the reclassified ER and PR scores, resulting in three groups: CER negative, impaired and high. Cox proportional hazards models were used to estimate disease-free survival (DFS) and breast cancer-specific survival (BCSS).

Results: The CER was a more powerful predictor of 5-year DFS and BCSS than either ER or PR alone. In multivariate analysis that included ER, PR and CER, only CER remained an independent prognostic variable for 5-year DFS (hazard ratio (HR) 0.393; CI: 0.283-0.548, P=0.00001) and BCSS (HR 0.553; CI: 0.423-0.722; P=2.506 × 10-8). In ER-positive (ER+) patients impaired CER was an independent marker of poor outcome for 5-year DFS (HR 2.469; CI: 1.049-5.810; P=0.038) and BCSS (HR 1.946; CI: 1.054-3.596; P=0.033) in multivariate analysis that included grade, lymph node, tumour size, HER2 status and PR status. The results were validated in a separate cohort of patients.

Conclusions: Combined endocrine receptor is a more powerful discriminator of patient outcome than either ER or PR alone. Economical and simple, it can identify risk in ER+ early breast cancer and potentially be used for adjuvant cytotoxic chemotherapy decision-making.