The primary purpose of this single-center, retrospective, observational cohort study was to assess the impact of PR negativity on oncologic outcome in ER+ BC patients. A secondary purpose of this study was to compare the presentation and clinicopathological features of ER+/PR+ and ER+/PR- BCs and to determine the associations and predictors of PR- disease.

Patients aged 50 to 70 years who presented either symptomatically or through BreastCheck, Ireland's national mammography-based breast screening, between January 2005 and December 2015 were included in the study. ER and PR status was routinely analyzed, as was human epidermal growth factor receptor (HER2) receptor status. Data were gathered on BC recurrence, overall survival (OS), and disease-free survival (DFS), which was defined as freedom from invasive disease recurrence. 

A total of 2,660 consecutive patients who were diagnosed with ER+ BC were studied. Of these, 83% were PR+ and 17% were PR-. The mean age at diagnosis was 59.6 years, with 71.4% being postmenopausal at diagnosis. More than three-quarters of patients were symptomatic at the time of diagnosis. Mean follow-up was 97.2 months.

Using binary logistic regression, investigators found that being postmenopausal at the time of diagnosis (odds ratio [OR] 1.66), presenting with symptoms (OR 1.71), having invasive ductal carcinoma subtype (OR 1.51), and having grade 3 tumors (OR 2.20) were predictors of PR- status. Treatment characteristics between those with a PR+ and PR- status were similar for the use of neoadjuvant chemotherapy, having undergone primary surgery and axillary surgery, and the use of adjuvant chemotherapy and radiotherapy.


Significant differences between the PR groups existed in terms of Oncotype DX Risk Score (RS) and in terms of whether adjuvant endocrine hormonal therapy (EHT) was administered. The mean Oncotype DX RS in PR+ patients was 17.5 and the median was 16, whereas in the PR- group these scores were 24.2 and 24, respectively, indicating higher risk of recurrence in the latter group (P <.001). PR status is part of the genomic panel in the gene assay OncogeneDX. EHT was administered in 98.4% of PR+ cases but in only 96.7% of PR- cases (P = .008).

Median OS, 5-year OS, DFS, and 5-year DFS were 84 months, 88.9%, 81 months, and 90.3%, respectively. There was no difference in local recurrence rates between patients who were PR+ and those who were PR-. However, the rate of distant recurrences was 11.7% in those who were PR+ but 15.0% in those who were PR- (P = .049). PR- patients also had a significantly worse 5-year DFS (91.0% vs. 85.8%) and OS (90.0% vs. 83.9%) compared with PR+ patients.

PR- status decreased DFS approximately 1.6-fold and OS by about 1.8-fold. Patients who were both PR- and HER2- had worse 5-year DFS and 5-year OS compared with those who were PR+ and HER2- (85.7% vs. 89.6%, P = .059, and 82.0% vs. 91.0%, P = .004, respectively). In patients who were HER2+, PR status did not impact survival.

Independent predictors of both worse DFS and worse OS included age >65 years at diagnosis, being symptomatic at presentation, grade 3 tumor, clinical nodal stage, and requiring a mastectomy. Additional predictors of worse OS included being postmenopausal at diagnosis and clinical tumor stage. On the other hand, receiving radiation therapy predicted improved OS.

This paper stresses the important prognostic role that PR- status has in overall DFS and OS in this population. Pharmacists need to consider PR status, not just ER status, when making treatment recommendations for patients with BC.

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