Molecular Mechanism and Clinical Implications of Endocrine Therapy Resistance in Breast CancerArpino G. · De Angelis C. · Giuliano M. · Giordano A. · Falato C. · De Laurentiis M. · De Placido S.
Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università di Napoli Federico II, Napoli, Italy
Endocrine therapy, the first targeted therapy in oncology, is the most successful systemic therapy in the management of estrogen receptor (ER)-positive breast cancer. Approximately 50% of patients with advanced disease do not respond to first-line treatment with tamoxifen, and many women who receive tamoxifen as adjuvant therapy experience tumor relapse and die from their disease. Aromatase inhibitors are proving superior to tamoxifen, at least in certain patient subsets. However, the response rate to these compounds is only slightly higher than that to tamoxifen in patients with advanced breast cancer, and both de novo or acquired resistance also occur, limiting the efficacy of the treatment. Advanced studies of ER biology have highlighted the role of an intimate cross talk between the ER and HER2/growth factor signaling pathways as a fundamental contributor to the development of resistance to hormone therapies. The aim of this review article is to summarize the current knowledge on mechanisms of resistance of breast cancer cells to endocrine therapies due to the cross talk between the ER and growth factor signaling pathways, and to explore newly available therapeutic strategies that could prolong duration of response and circumvent endocrine-resistant tumor growth.
© 2010 S. Karger AG, Basel
Published online: February 2, 2010
Number of Print Pages : 15
Number of Figures : 2, Number of Tables : 2, Number of References : 116
Oncology (International Journal of Cancer Research and Treatment)
Vol. 77, No. Suppl. 1, Year 2009 (Cover Date: February 2010)
Journal Editor: Markman M. (Houston, Tex.)
ISSN: 0030-2414 (Print), eISSN: 1423-0232 (Online)
For additional information: http://www.karger.com/OCL