Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women

Abstract

Background Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use for many years. Aromatase inhibitors (AIs) are a class of compounds that systemically inhibit oestrogen synthesis in the peripheral tissues. Aminoglutethimide was the first AI in clinical use (first generation) and had a similar tumour-regressing effect to other endocrine treatments, which showed the potential of this alternative type of therapy. Other AIs have since been developed and the third generation AIs anastrozole, exemestane and letrozole are in current use. Randomised evidence on response rates and side effects of these drugs is still limited. Objectives To compare aromatase inhibitors to other endocrine therapy in the treatment of advanced breast cancer in postmenopausal women. Search strategy The Cochrane Breast Cancer Group Specialised Register was first searched on 3 December 2004 using the codes for "advanced" and "endocrine therapy". Details of the search strategy applied to create the Register and the procedure used to code references are described in the Cochrane Breast Cancer Group module on The Cochrane Library. The search was updated to 30 September 2005 and additional publications were included. Experts were consulted to determine that no relevant studies had been excluded. Selection criteria Randomised trials comparing the effects of any aromatase inhibitor versus other endocrine therapy, no endocrine therapy or a different aromatase inhibitor in the treatment of advanced (metastatic) breast cancer. Data collection and analysis Data from published trials were extracted by two independent review authors. A third independent author then carried out a further cross check for accuracy and consistency. Hazard ratios (HR) were derived for analysis of time-to-event outcomes (overall and progressionfree). Odds ratios (OR) were derived for objective response and clinical benefit (both analysed as dichotomous variables). Toxicity data were extracted where present and treatments were compared using odds ratios. All but one of the studies included data on one or more of the following outcomes: overall survival, progression-free survival, clinical benefit and objective response.

Predictors of non-adherence to aromatase inhibitors among commercially insured women with breast cancer

“…These drugs suppress estradiol levels in post-menopausal women by 84% or more [6] and are replacing the long-term use (C5 years) of tamoxifen among women with hormonal-sensitive receptive postmenopausal breast cancer due to better efficacy and more favorable safety profile [3,4]. Given an observed survival benefit among women with metastatic breast cancer [7], AIs are also being used clinically for metastatic disease.…”

Chemotherapy for metastatic breast cancer. Comparison of clinical practice and cost of drugs in two cohorts of patients: 1994–1998 and 2003–2006

“…This is probably related to the use of new hormonal therapies approved for MBC patients during the last decade such as aromatase inhibitors [28] and LH-RH agonists combined with tamoxifen [29,30]; these drugs have demonstrated a significant survival benefit over other endocrine therapies.…”

The Expanding Use of Third-Generation Aromatase Inhibitors: What the General Internist Needs to Know

“…10 A 2007 Cochrane review of 25 studies comparing AIs to other endocrine therapies in the treatment of metastatic breast cancer showed a significant survival benefit of AIs (HR = 0.89; 95% CI, 0.82-0.96). 11 Although there does not appear to be a benefit in combining tamoxifen with AIs, studies of AIs given before, after, or in place of tamoxifen for the treatment of early-stage breast cancer found AIs to be superior to tamoxifen monotherapy in DFS (Table 1). [6][7][8][12][13][14][15] Consequently, current guidelines recommend the use of AIs at some time during treatment of hormoneresponsive postmenopausal breast cancer.…”