Prediction of hormone sensitivity for breast cancers

• Published in: Breast cancer (Tokyo, Japan) Vol. 17; no. 2; pp. 86 - 91
• Main Authors: Miyoshi, Yasuo, Murase, Keiko, Saito, Masaru, Oh, Koushi
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.04.2010; Springer
• Subjects: Animals; Antineoplastic Agents, Hormonal - therapeutic use; Biomarkers, Tumor - analysis; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer Research; Drug Resistance, Neoplasm; Estrogen; Female; Fulvestrant; Genetic aspects; Genetic transcription; Hormones; Humans; Medicine; Medicine & Public Health; Oncology; Prognosis; Receptors, Estrogen - metabolism; Special Feature; Surgery; Surgical Oncology; Tamoxifen; Breast cancer; Signaling pathway; Hormonal therapy; Growth factor
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-009-0177-x

The classic action that leads to transcriptional activation of estrogen response genes mediated through estrogen receptors (ER) and the estrogen complex plays a pivotal role in the development of ER-positive breast cancers. In addition to this pathway, non-classic action and non-genomic action, both estrogen-dependent and estrogen-independent genomic actions have also been found to contribute to ER-positive tumor growth. Although the details of these mechanisms are not well known, participation of the growth factor signaling pathway is likely to be the most significant factor for acquisition of resistance to hormonal therapy. This resistance is mediated not only directly through cell growth promotion by growth factor signaling, but also through enhancement of alternative ER signaling pathways in addition to classic action. The reason why tamoxifen-insensitive ER-positive breast cancers respond to aromatase inhibitors may be explained, at least in part, by the different estrogen-related signaling pathways in which aromatase inhibitors may block estrogen signaling. In this paper we discuss the molecular mechanisms for resistance to hormonal therapy based on an understanding of estrogen signaling pathways.