title: Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo - Meta-analyses on efficacy and adverse events based on randomized clinical trials.
abstract: Tamoxifen (TAM) and aromatase inhibitors (AI) are adjuvant therapy options for postmenopausal women with estrogen receptor positive (ER+) breast cancer. This systematic review of seven randomized controlled studies comparing TAM and AI, and one study comparing extended therapy with an AI with placebo after about 5 years of tamoxifen, aims to assess long-term clinical efficacy and adverse events. The literature review was performed according to the principles of the Cochrane Collaboration. The search included common databases up to 2013-01-14. Studies of high or moderate quality were used for grading of evidence. Revman™ software was utilized for meta-analyses of published data. Disease free survival (DFS) and overall survival (OS) were improved with AI monotherapy compared to TAM with high and moderate quality of evidence respectively. Sequenced therapy with AI → TAM (or vice versa) improved DFS compared with TAM with moderate quality of evidence, but did not improve OS (low quality of evidence). However, if only studies on sequenced AI therapy with randomization before endocrine therapy were considered, no improvement of DFS could be found. Fractures are more frequently associated with AI whereas the risk of endometrial cancer and venous thromboembolism are higher with TAM. For cardiovascular events no difference was found between AI (mono- or sequenced therapy) and TAM, whereas sequenced therapy compared with AI had lower risk of cardiovascular events (moderate level of evidence). AIs are superior to TAM as adjuvant hormonal therapy for postmenopausal ER-positive breast cancer. TAM can be considered for individual patients due to the different toxicity profile compared with AI. Cardiovascular events related to AI treatment deserve further attention.
authors.affiliation: Department of Surgery, Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: lisa.ryden@med.lu.se.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Swedish Council on Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden; Medical Management Centre/LIME, Karolinska Institutet, Stockholm, Sweden; Faculty of Health and Society, Department of Nursing Science, Malmö University, Sweden. Electronic address: heibert.arnlind@sbu.se.
authors.forename: Marianne
authors.initials: M
authors.lastname: Heibert Arnlind
authors.affiliation: Swedish Council on Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden; Department of Medicine, Clinical Pharmacological Unit, Karolinska Institutet, Stockholm, Sweden. Electronic address: vitols@sbu.se.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Vitols
authors.affiliation: Swedish Council on Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden; Medical Management Centre/LIME, Karolinska Institutet, Stockholm, Sweden. Electronic address: hoistad@sbu.se.
authors.forename: Malin
authors.initials: M
authors.lastname: Höistad
authors.affiliation: Department of Oncology, University of Örebro, Örebro, Sweden. Electronic address: johan.ahlgren@regionorebrolan.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Ahlgren
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D047072:Aromatase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000139:chemically induced; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D013629:Tamoxifen
keywords: Adverse events; Aromatase inhibitors; Early breast cancer; Randomized clinical trial; Systematic review; Tamoxifen