Tumour and cellular distribution of activated forms of PR in breast cancers: a novel immunohistochemical analysis of a large clinical cohort

• Published in: ESMO open 2016, Vol.1 (4), p.e000072-e000072, Article e000072
• Main Authors: Bonneterre, Jacques, Bosq, Jacques, Jamme, Philippe, Valent, Alexander, Gilles, Erard M, Zukiwski, Alexander A, Fuqua, Suzanne A W, Lange, Carol A, O'Shaughnessy, Joyce
• Format: Article
• Language: English
• Subjects: activated; breast cancer; onapristone; Original Research; progesterone receptor
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2016-000072

BackgroundThe progesterone receptor (PR) is expressed by ∼70% of early breast tumours and is implicated in the progression of breast cancer. In cancerous tissues PR may be activated in the absence of a ligand, or when ligand concentrations are very low, resulting in aberrantly activated PR (APR). The presence of APR may indicate that patients with breast cancer are more likely to respond to antiprogestins. The aims of this study were to describe and classify the histological subnuclear morphology of active and inactive PR in archival breast cancer samples.MethodsArchived tumour specimens from 801 women with invasive breast cancer were collected. Tissue samples (n=789) were analysed for PR isoforms A and B (PRA and PRB), Ki67 and estrogen receptors (ERα) status, using immunohistochemistry. Medical records were used to determine human epidermal growth factor 2 (HER2) status, tumour stage and grade.ResultsA total of 79% of tumours stained positive for either PRA or PRB, and of these 25% of PRA-positive and 23% of PRB-positive tumours had PR present in the activated form. APRA was associated with higher tumour grade (p=0.001). APRB was associated with a higher tumour grade (p=0.046) and a trend for a more advanced stage. Patients with PR-positive tumours treated with antiestrogens had better disease-free survival (DFS) than those with PR-negative tumours (p