Advanced (or metastatic) breast cancer is cancer that has spread beyond the breast and regional lymph node areas. Breast cancer can progress to metastatic disease despite the person undergoing a range of therapies given after initial treatment, such as surgery, chemotherapy or radiation therapy. Metastatic breast cancer is treatable but it is not curable. Most breast cancer is sensitive to the female hormone oestrogen. Sensitive cancer cells need oestrogen to stay alive and removal of oestrogen from the body, or stopping any circulating oestrogen getting to the cancer cells, is very effective treatment for hormone-sensitive breast cancers. Endocrine (hormonal) therapy removes the influence of oestrogen on breast cancer cells. Hormonal treatments for advanced breast cancer include tamoxifen, the progestins megestrol acetate and medroxyprogesterone acetate, and aromatase inhibitors (AIs). AIs reduce the body's ability to make (synthesise) oestrogen and have tumour-regressing effects. The AIs in current clinical use include anastrozole, exemestane, and letrozole.
The aim of this systematic review was to compare AIs to other endocrine therapy in the treatment of advanced (metastatic) breast cancer. A systematic search was conducted which identified 37 controlled trials in which over 14,000 women were randomised to treatment groups. Treatment with an AI improved survival for women with metastatic disease by 10%. The overall benefits on disease-free survival and response of the tumour were however unclear based on the studies included in this review. Trials using AIs as first-line and second-line therapy reported benefits of therapy that varied with the different AIs and measures of effectiveness. We were unable to identify specific subgroups of women who may benefit from AI use.
Toxicity (negative side effects) was not well reported in the trials. Where it was reported, there was variation as to the method used for reporting, the type of toxicities reported, as well as the criteria used to assess toxicity. Nevertheless, toxicity data were available for 26 of the 32 trials where an AI was compared with a non-AI. AIs had similar levels of arthritic pain (arthralgia) and hot flushes (especially when compared to tamoxifen); increased risks of rash, diarrhoea, nausea and vomiting; but decreased risk of vaginal bleeding and blood clotting (thromboembolic) events compared with other endocrine therapies. Limited quality of life (QOL) data were provided and, as such, no conclusions can be drawn by this review as to the effect on QOL related to an AI versus a non-AI. This is due to the differences between participants and the side-effect profiles of the agents used, different methods of drug application (injection versus tablets), and use of four different QOL instruments at several different timepoints, some which provided results of responders versus non-responders rather than by treatment group. Some QOL measures were based on clinician-reported rather than patient-reported symptoms.