Risk Factors for Disease Recurrence in Patients with HER2+ Early Breast Cancer and Implications for Therapy: A Narrative Review

Human epidermal growth factor receptor 2 (HER2) overexpression or amplification of the human ERBB2 oncogene occurs in approximately one-fifth of breast cancers and, of these, two-thirds are hormone receptor (HR)-positive (HR+). The introduction of HER2-targeted therapies in recent years has significantly improved survival outcomes in patients with this tumor subtype. However, disease recurrence risk is 10–30% at 5 years with a different pattern between patients with HER2+/HR+ and HER2+/HR-negative (HR−) early breast cancer, with HR+ patients having a lower risk than those with HR− disease in the first 5 years, but a slightly higher risk at 5–10 years post-surgery. This highlights a crucial need to explore the underlying mechanisms for these differences to address specific treatment needs and to optimize systemic adjuvant treatment outcomes. Therefore, this narrative review provides an overview of published data regarding the recognized factors and ongoing challenges associated with the risk of relapse in women with HER2+ early breast cancer and proposes potential adjuvant treatment strategies to minimize risk of recurrence in high-risk patients.