The expanding use of third-generation aromatase inhibitors: what the general internist needs to know.

backgroundBreast cancer patients represent the largest group of adult cancer survivors in the US. Most breast cancers in women 50 years of age and older are hormone receptor positive. Third generation aromatase inhibitors (AIs) are the newest class of drugs used in treating hormone responsive breast cancer. It is often during start of adjuvant hormone therapy that the breast cancer patient establishes (or reestablishes) close follow-up with their general internist.

objectiveGiven the large numbers of breast cancer patients in the US and the increasing use of third generation AI's, general internists will need to have a clear understanding of these drugs including their benefits and potential harms. Currently there are three third generation aromatase inhibitors FDA approved for use in the US. All have been shown to be superior to tamoxifen in disease free survival (DFS) in the treatment of both metastatic and early breast cancers.

resultsWhile the data on side effects is limited, AI (compared to tamoxifen) may result in higher rates of osteoporosis and fractures, more arthralgias, and increased vaginal dryness and dysparuenia. Limited information on their effects on the cardiovascular system and neuro-cognitive function are also available. Patient's receiving adjuvant hormone therapy are generally considered disease free or disease stable and require less intensive monitoring by their breast cancer specialist.

conclusionsIn situations where patients experience significant negative side effects from AI therapy, discussions to discontinue treatment (and switch to an alternative endocrine therapy) should involve the cancer specialist and take into consideration the patient's risk for breast cancer recurrence and the impact of therapy on their quality of life. In some cases, patients may choose to never initiate AI treatment. In other cases, patients may choose to prematurely discontinue therapy even if therapy is well tolerated. In both settings increased knowledge by the general internists will likely facilitate discussions of risks versus benefits of therapy and possibly improve compliance to adjuvant hormone therapy.