Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients

The human epidermal growth factor-2 (HER2) gene is overexpressed in 15-20 % of all breast cancers. HER2 overexpression is a predictive factor in breast cancer and is associated with high rates of disease recurrence and death in the absence of adjuvant systemic therapy. With the advent of HER2-directed therapies, there has been a significant improvement in the outcome of HER2-positive (HER2+) breast cancer in all clinical settings. Patients aged > 65 years remain under-represented in most clinical trials. Existing literature suggests that older patients with HER2+ disease derive a similar benefit from anti-HER2 therapies as do their younger counterparts, in both adjuvant and metastatic settings. Cardiotoxicity from HER2-directed therapy is a major concern with older patients, especially in the setting of pre-existing co-morbidities. Older patients need a geriatric assessment before beginning any systemic therapy, to identify patients predisposed to developing toxicity and to plan therapy. Many onco-geriatric tools have been developed to further identify frail patients. In this article, we discuss the most up-to-date clinical data on existing therapies for HER2+ breast cancer in adjuvant, neoadjuvant, and metastatic settings, and their application in older patients. We attempt to highlight clinical benefits and toxicities in this group that may aid clinicians in therapeutic decision making.