Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women

Abstract

The present meta-analysis examines randomized trials of third-generation aromatase inhibitors (AIs) as alternatives to tamoxifen in three treatment settings: monotherapy, sequenced therapy and extended therapy. Eleven randomized controlled trials (RCTs) were chosen based on their similarity in terms of study design and included 34,070 post-menopausal women who had undergone surgery for estrogen-sensitive early breast cancer. DFS was significantly improved by AI monotherapy (Hazard Ratio (HR): 0.89, p = 0.001), sequenced therapy (HR: 0.7, p < 0.00001) and extended therapy (HR: 0.62, p < 0.00001). All of the patients benefited significantly from sequenced therapy (HR: 0.81, p = 0.003), and hormone receptor-positive patients benefited from AI monotherapy (HR = 0.92, p = 0.046) with respect to OS. AI monotherapy conferred significantly lower risks for thromboembolic events (OR = 0.61; p < 0.001) and endometrial cancer (OR = 0.26; p < 0.001) compared with tamoxifen monotherapy; however, there was a greater risk of cardiovascular events (OR = 1.20; p = 0.030). Sequenced therapy was also superior in terms of endometrial cancer but was inferior with respect to fractures, thromboembolic and cardiovascular events.

Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis

“…Compared with Tamoxifen, third generation aromatase inhibitors have been shown to significantly improve disease free survival (DFS) (2)(3)(4), and include the steroidal inhibitor exemestane, and the nonsteroidal inhibitors, anastrozole and letrozole. In the 2013 meta-analysis by Aydiner et al (5), five years of adjuvant therapy with aromatase inhibitors improved DFS (HR 0.89, p=0.001), and also overall survival (OS) (HR 0.92, p=0.046) when compared to tamoxifen.…”

“…Aromatase inhibitors have also demonstrated improvement in DFS, OS and distant metastasis rate when sequenced with tamoxifen (HR 0.70, p<0.001; HR 0.81, p=0.003, HR 0.74, p<0.001 respectively), and an improvement in DFS as extended adjuvant treatment after 5 years of tamoxifen (HR 0.62, p=0.001) (5). Recent evidence has revealed a benefit of continuing aromatase inhibitors for a period of 10 years, as reported in the MA.17R trial, which displayed significant improvement in breast cancer recurrence rates, and decreased contralateral breast cancer (6).…”

Cardiovascular disease in cancer survivors

“…A 2013 meta-analysis of randomised trials of third-generation aromatase inhibitors as alternatives to tamoxifen involved ∼34 000 patients and showed higher risk of cardiovascular events (OR=1.20; p=0.030), compared with tamoxifen monotherapy 38. In the same study, the absolute risk of cardiovascular events with either drug was low at 4.2% with aromatase inhibitors and 3.4% with tamoxifen.…”

Prediction of Response to Aromatase Inhibitors in Breast Cancer

“…Most clinical trials comparing the adjuvant use of AIs versus tamoxifen have consistently shown clinical benefit in favour of AIs [12][13][14]. Effects on disease recurrence are usually statistically significant whereas those on survival are rarely so, unless trials are combined in a meta-analysis [20,21]. These studies also suggest that benefits of AIs are not evident in all patients but more apparent in certain subgroups.…”