The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer

Background: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. Methods: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. Results: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P<0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P<0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P=0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P<0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P=0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P=0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P<0.001), as well as worse overall survival in ER+/HER2- disease (P=0.004). Conclusions: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.