Critical Reviews™ in Oncogenesis

ISSN for PRINT: 0893-9675

For Online Access

Best Paper Award Selection - Editorial Board Site

2007, Volume13

Orla Mc Cormack
UCD School of Medicine and Medical Science (SMMS), University College Dublin, Belfield, Dublin 4, Ireland, and UCD Conway Institute of Biomolecular & Biomedical Science, UCD, Bel-field, Dublin 4, Ireland

Michele Harrison
Department of Pathology, Mater Misericordiae Hospital, Eccles St., Dublin 7, Ireland

Michael J. Kerin
UCD School of Medicine and Medical Science,University College Dublin,Belfield,Dublin 4; UCD Conway Institute of Biomolecular & Biomedical Science, UCD, Bel-field, Dublin 4; and Clinical Science Institute,University College Hospital Galway, Ireland

Amanda McCann
UCD School of Medicine and Medical Science (SMMS), University College Dublin, Belfield, Dublin 4, Ireland, and UCD Conway Institute of Biomolecular & Biomedical Science, UCD, Bel-field, Dublin 4, Ireland

Known risk factors for breast cancer include overexposure to exogenous or endogenous hormones, namely, estrogen and progesterone. The effects of progesterone acts via two isoforms of the progesterone receptor (PR) termed A (PRA) and B (PRB). There is a single human PR gene with two distinct promoter regions in exon 1 encoding the two isoforms. Studies have shown that in poor prognostic tumors, the ratio between PRA and PRB is altered, with a predominance of PRA and loss of PRB. PRA and PRB regulate different subsets of genes involved in particular functional pathways. Breast tumors that express PR are associated with slow growth, better differentiation, and better overall prognosis in the short term. Both estrogen receptor alpha (ERα) and total progesterone receptor (PR) are immunohistochemically measured on breast cancer specimens to help determine those patients who would benefit from hormonal treatment. Depending on the hormone receptor status and the menopausal status of the patient, different treatments are available. Although the value of ERα in predicting response to hormone therapy in early breast cancer patients is undisputed, the value of PR is currently under debate. Historically, PR was thought to be a surrogate marker for ER expression; however, it is now known that lack of PR expression can indicate underlying epidermal growth factor receptor signaling or promoter methylation. This has implications for and can dictate hormone therapy responsiveness. Further studies investigating the specific isoforms and their pathways will help to reveal the underlying mechanisms of PR-induced breast tumori-genesis and help in assigning the most appropriate patient-tailored treatment.

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