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An overview of letrozole in postmenopausal women with hormone-responsive breast cancer.
Adv Ther. 2011 Dec; 28(12):1045-58.AT

Abstract

Third-generation aromatase inhibitors (AIs) have proven to be superior to tamoxifen in terms of time to disease progression in patients with hormone receptor (HR) positive (HR+) status and, nowadays, are used in the adjuvant and neoadjuvant settings, and first-line therapy for advanced breast cancer. Letrozole is a third generation AI, as are anastrozole and exemestane. In the past, clinical studies had demonstrated that letrozole was effective as a second-line treatment of metastatic breast cancer. In this paper, pharmacokinetic and pharmacodynamic properties of letrozole are reviewed along with its activity in preclinical and clinical settings. Additionally, the results of important clinical trials such as Breast International Group (BIG) 1-98, which tested the optimal initial adjuvant endocrine treatment and the sequential therapy with letrozole and tamoxifen, MA-17 that evaluates the benefits of extended adjuvant therapy, and other important studies in advanced and neoadjuvant disease, are reviewed. Safety comparisons of treatments are also addressed. Interestingly, about 50% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers are HR+. However, HER2 positivity is a marker of antiestrogen treatment resistance. Because of this, a dual treatment is a logical approach when both receptors are overexpressed. The combination of lapatinib and letrozole leads to a significant improvement in the overall disease outcome. Also, the combination of everolimus plus letrozole has been tested in this setting. In fact, the coadministration of both agents seems to increase the efficacy of letrozole in newly-diagnosed HR+ patients. Once resistance to sequential trastuzumab and AI as monotherapy has been found, trastuzumab and letrozole combined in HR+ and HER2+ patients with advanced breast cancer can overcome resistance to both drugs administered as single agents, according to recently reported results.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Barnadas A
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. abarnadasm@santpau.cat
Estévez LG
No affiliation info available
Lluch-Hernández A
No affiliation info available
Rodriguez-Lescure A
No affiliation info available
Rodriguez-Sanchez C
No affiliation info available
Sanchez-Rovira P
No affiliation info available

MeSH

AndrogensAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsBone and BonesBreast NeoplasmsClinical Trials as TopicCytochrome P-450 Enzyme SystemEstrogen Receptor ModulatorsFemaleHumansLetrozoleLipidsNitrilesPostmenopauseTamoxifenTriazoles

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22068628

Citation

Barnadas, Agustí, et al. "An Overview of Letrozole in Postmenopausal Women With Hormone-responsive Breast Cancer." Advances in Therapy, vol. 28, no. 12, 2011, pp. 1045-58.
Barnadas A, Estévez LG, Lluch-Hernández A, et al. An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. Adv Ther. 2011;28(12):1045-58.
Barnadas, A., Estévez, L. G., Lluch-Hernández, A., Rodriguez-Lescure, A., Rodriguez-Sanchez, C., & Sanchez-Rovira, P. (2011). An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. Advances in Therapy, 28(12), 1045-58. https://doi.org/10.1007/s12325-011-0075-4
Barnadas A, et al. An Overview of Letrozole in Postmenopausal Women With Hormone-responsive Breast Cancer. Adv Ther. 2011;28(12):1045-58. PubMed PMID: 22068628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. AU - Barnadas,Agustí, AU - Estévez,Laura G, AU - Lluch-Hernández,Ana, AU - Rodriguez-Lescure,Alvaro, AU - Rodriguez-Sanchez,César, AU - Sanchez-Rovira,Pedro, Y1 - 2011/11/07/ PY - 2011/06/16/received PY - 2011/11/10/entrez PY - 2011/11/10/pubmed PY - 2012/5/4/medline SP - 1045 EP - 58 JF - Advances in therapy JO - Adv Ther VL - 28 IS - 12 N2 - Third-generation aromatase inhibitors (AIs) have proven to be superior to tamoxifen in terms of time to disease progression in patients with hormone receptor (HR) positive (HR+) status and, nowadays, are used in the adjuvant and neoadjuvant settings, and first-line therapy for advanced breast cancer. Letrozole is a third generation AI, as are anastrozole and exemestane. In the past, clinical studies had demonstrated that letrozole was effective as a second-line treatment of metastatic breast cancer. In this paper, pharmacokinetic and pharmacodynamic properties of letrozole are reviewed along with its activity in preclinical and clinical settings. Additionally, the results of important clinical trials such as Breast International Group (BIG) 1-98, which tested the optimal initial adjuvant endocrine treatment and the sequential therapy with letrozole and tamoxifen, MA-17 that evaluates the benefits of extended adjuvant therapy, and other important studies in advanced and neoadjuvant disease, are reviewed. Safety comparisons of treatments are also addressed. Interestingly, about 50% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers are HR+. However, HER2 positivity is a marker of antiestrogen treatment resistance. Because of this, a dual treatment is a logical approach when both receptors are overexpressed. The combination of lapatinib and letrozole leads to a significant improvement in the overall disease outcome. Also, the combination of everolimus plus letrozole has been tested in this setting. In fact, the coadministration of both agents seems to increase the efficacy of letrozole in newly-diagnosed HR+ patients. Once resistance to sequential trastuzumab and AI as monotherapy has been found, trastuzumab and letrozole combined in HR+ and HER2+ patients with advanced breast cancer can overcome resistance to both drugs administered as single agents, according to recently reported results. SN - 1865-8652 UR - https://www.unboundmedicine.com/medline/citation/22068628/An_overview_of_letrozole_in_postmenopausal_women_with_hormone_responsive_breast_cancer_ L2 - https://dx.doi.org/10.1007/s12325-011-0075-4 DB - PRIME DP - Unbound Medicine ER -