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

Abstract

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.

Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer

“…Furthermore, the discovery and development of diagnostic, prognostic and therapeutic biomarkers have transformed the international perception such that at least four heterogeneous molecular subtypes are recognised in clinical practice [11,12]. Distinguishing these subtypes relies on the genetic expression of estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, and Ki-67 proliferation indices due to their critical role in the substratification, prognostication, and personalization of treatment modalities for each subtype [10,[12][13][14][15][16][17][18][19]. Mandatory ER, PgR, and HER2 immunohistochemical appraisals are recommended to approximate the genetic expression of these in all cases of invasive breast cancer according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines [20,21], as these are established predictive and prognostic biomarkers in breast oncology, proving crucial in therapeutic decision making [18,[22][23][24].…”

“…Distinguishing these subtypes relies on the genetic expression of estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, and Ki-67 proliferation indices due to their critical role in the substratification, prognostication, and personalization of treatment modalities for each subtype [10,[12][13][14][15][16][17][18][19]. Mandatory ER, PgR, and HER2 immunohistochemical appraisals are recommended to approximate the genetic expression of these in all cases of invasive breast cancer according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines [20,21], as these are established predictive and prognostic biomarkers in breast oncology, proving crucial in therapeutic decision making [18,[22][23][24]. Additionally, Ki-67 proliferation indices remain critical in the 2011 St. Gallen Consensus for differentiating Luminal A and Luminal B molecular subtypes [12].…”

Lost but Not Least—Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer

“…On the other hand, PgR-negativity in ERα(+) BC is associated with higher rates of pathological complete response to neoadjuvant chemotherapy (NAC) when compared to double-positive BC [ 26 , 27 , 28 ]. Thus, PgR status may be of great importance in predicting response to NAC in ERα(+) patients.…”

The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment

“…While the molecular era has shifted the paradigm toward encompassing intrinsic biological tumour parameters which inform treatment decisions and prognoses, the degree of disease burden remains paramount to preoperative surgical planning. The routine measurement of the ER, PgR, HER2 receptors and Ki-67 proliferation indices [ 62 , 63 , 64 ] furthers accurate prognostication through intrinsic molecular subtyping, with modern advances implicating features pertinent to the tumour microenvironment important in informing prognosis [ 65 ]. Several studies detail miRNA expression profiles in breast cancer tissue, outlining their importance in relation to nodal burden, disease recurrence and survival [ 58 , 66 , 67 ].…”