title: An overview of letrozole in postmenopausal women with hormone-responsive breast cancer.
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.
authors: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. abarnadasm@santpau.cat
authors: Agustí
authors: A
authors: Barnadas
authors: Laura G
authors: LG
authors: Estévez
authors: Ana
authors: A
authors: Lluch-Hernández
authors: Alvaro
authors: A
authors: Rodriguez-Lescure
authors: César
authors: C
authors: Rodriguez-Sanchez
authors: Pedro
authors: P
authors: Sanchez-Rovira
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D008055:Lipids / Q000097:blood; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D020847:Estrogen Receptor Modulators; D008055:Lipids; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole; D003577:Cytochrome P-450 Enzyme System