Clinical management of adverse events in adjuvant therapy for hormone-responsive early breast cancer

Systemic adjuvant therapy has proven highly effective at reducing recurrences and deaths in patients who have received primary therapy for early breast cancer. However, as with all treatments, adjuvant therapy can cause unwanted side effects, and effective management of these events is essential to ensure that patients comply with, and continue, treatment. Adjuvant endocrine therapy is not associated with the more severe, acute toxicities of chemotherapy, and can therefore be taken for many years. At present, the standard duration of postoperative adjuvant endocrine therapy is 5 years. Prevention and treatment of adverse events associated with long-term endocrine therapy is particularly important in the adjuvant setting, where patients are clinically cancer free. In this situation, the efficacy benefits are not, therefore, obvious to the patient, but side effects may have a negative impact on daily life. Tamoxifen has been the gold standard endocrine therapy for hormone-receptor-positive early breast cancer for many years, and the long-term side effects of this agent are well documented. In recent years, the aromatase inhibitors (Als) have begun to displace tamoxifen as the adjuvant therapy of choice, owing to greater efficacy and good tolerability. Predictably, the Als and tamoxifen have partially overlapping side-effect profiles. Both therapies are associated with typical symptoms of estrogen deprivation; however, tamoxifen also has estrogenic activity in some tissues, which can cause either detrimental (genital tract) or beneficial (bone, cardiovascular system, lipids) effects that are not associated with AI use. To reduce treatment discontinuations, it is important that patients are made aware of the possible side effects of adjuvant therapy and the management strategies available to them, prior to starting therapy. The role of physical, alternative and pharmaceutical therapies in the management of adverse events associated with endocrine therapy has been investigated, and strategies are now available to alleviate symptoms and enable patients to benefit from adjuvant endocrine therapy without a significant adverse impact on quality of life.