When hormone therapy fails, what happens next?

This analysis compared previous research to determine the most effective treatment for hormone receptor positive breast cancer patients whose disease has progressed despite initial treatment.  

Hormone receptor positive breast cancer depends on the hormones estrogen or progesterone for growth. The principle treatment for this type of breast cancer, therefore, is blocking either the production of the hormone, or the ability of the body to use these hormones. This is achieved with hormone therapies such as aromatase inhibitors; these drugs block the protein that produces estrogen. However, the best course of treatment for women whose cancer has progressed despite therapy with these inhibitors is not clear.

While using another form of estrogen inhibitor such as fulvestrant (Faslodex) is optional, it is also possible to combine aromatase inhibitors with other treatments. For instance, the aromatase inhibitor exemestane (Arimidex) has recently been used in combination with everolimus (Afinitor), a therapy that blocks the production of mTORC1, a protein important for cell growth, division and survival. Studies have shown that the combination of these two drugs doubled the time until disease progression in patients with advanced hormone receptor positive breast cancer. However, trials examining fulvestrant have also shown increased time until progression, and it is unclear which course may be the most effective.

The current analysis examined prior research on the exemestane/everolimus combination and fulvestrant, to determine which treatment is more effective for hormone receptor positive advanced breast cancer patients who have progressed despite treatment with an aromatase inhibitor.

This analysis compared 7 studies, including 3,945 patients. In each study, patients were postmenopausal women with locally advanced or metastatic (cancer that has spread) hormone receptor positive breast cancer. Some studies compared the effectiveness of exemestane plus everolimus to exemestane alone, while others compared fulvestrant to exemestane.

Overall, the exemestane/everolimus combination increased progression free survival times (the time following treatment before the disease progresses) more than other treatments examined.

The exemestane/everolimus combination was associated with a 53% decrease in the risk of progression during the study follow-up compared to 250mg of fulvestrant, and a 41% decrease in the risk of progression during the study follow-up compared to 500mg of fulvestrant. These results were similar in those patients who had progressed despite treatment with an aromatase inhibitor.

This analysis concluded that a combination of exemestane and everolimus was a more effective treatment than fulvestrant in hormone receptor positive breast cancer patients, particularly in those who had progressed despite treatment with an aromatase inhibitor.