The statements and recommendations about pre-menopausal women are based on evidence from a meta-analysis2 of four randomised trials. The trials compared the use of luteinising hormone-releasing hormone (LH-RH) agonist alone compared with the use of LH-RH agonist plus tamoxifen in pre-menopausal women with advanced breast cancer.
Combined therapy of LH-RH agonist plus tamoxifen significantly improved overall survival and progression-free survival compared with LH-RH agonist alone in pre-menopausal women with advanced breast cancer. Another trial5 found a significant improvement in survival outcomes for women treated with combined LH-RH agonist plus tamoxifen compared with tamoxifen alone. This trial also found a significantly reduced incidence of hot flushes in women treated with tamoxifen alone.
All trials investigating the use of endocrine therapy in pre-menopausal women used a LH-RH agonist. Although not formally compared in a trial setting, it is reasonable to assume that all forms of ovarian ablation or ovarian functional suppression are equivalent and have similar effects.
The statements and recommendations about post-menopausal women are based on evidence from 14 randomised trials assessing the use of endocrine therapy for post-menopausal women with hormone receptor-positive advanced breast cancer:
- five trials compared a third generation aromatase inhibitor with tamoxifen as first-line therapy6-10
- five trials compared a third generation aromatase inhibitor with progestins (megestrol acetate) as second-line therapy11-15
- two trials compared a third generation aromatase inhibitor with fulvestrant as second-line therapy16,17
- two trials compared one third generation aromatase inhibitors with another.18,19
As first-line therapy, aromatase inhibitors significantly improved progression-free survival and overall response rate compared with tamoxifen in post-menopausal women with hormone receptor-positive advanced breast cancer. Improvements in overall survival have not been demonstrated. Overall, there was no significant difference in total adverse events between aromatase inhibitors and tamoxifen, although the incidence of vaginal bleeding and thromboembolic events was significantly lower in women treated with aromatase inhibitors. One study reported that quality of life was comparable for aromatase inhibitors and tamoxifen.3
As second-line therapy, aromatase inhibitors significantly improved progression-free survival and overall survival for women compared with progestins. Overall, both treatments were well tolerated. Patients treated with aromatase inhibitors experienced significantly higher incidence of nausea, hot flushes, and diarrhoea but a significantly lower incidence of dyspnoea compared with patients treated with progestins. Where reported, quality of life data comparing aromatase inhibitors and progestins are conflicting and no firm conclusions can be drawn. There were no significant differences in efficacy or safety with the use of aromatase inhibitors compared with fulvestrant.3
Of the two trials that compared one aromatase inhibitor with another, treatment was administered first-line in one trial18 and second-line in the other19 Superiority of one aromatase inhibitor over another is yet to be determined.
* In February 2008, National Breast Cancer Centre (NBCC), incorporating the Ovarian Cancer Program, changed its name to National Breast and Ovarian Cancer Centre (NBOCC). In July 2011, NBOCC amalgamated with Cancer Australia to form a single national agency, Cancer Australia, to provide leadership in cancer control and improve outcomes for Australians affected by cancer.