Risk of Recurrence in Patients With HER2+ Early-Stage Breast Cancer: Literature Analysis of Patient and Disease Characteristics

Human epidermal growth factor receptor 2 (HER2) overexpression occurs in 15% to 20% of patients with early-stage breast cancers (EBCs). Without HER2-targeted therapy, 30% to 50% of patients relapse within 10 years, many developing incurable metastatic disease. This literature review was designed to identify and validate patient- and disease-related factors associated with recurrence in patients with HER2+ EBC. Peer-reviewed primary research articles and congress abstracts were identified by searching MEDLINE. Articles published in English from 2019 to 2022 were included to identify contemporary treatment options. Results were analyzed for the relationship between risk factors and surrogates of HER2+ EBC recurrence to determine how identified risk factors affected HER2+ EBC recurrence. Sixty-one articles and 65 abstracts that assessed age at diagnosis, body mass index (BMI), tumor size at diagnosis, hormone receptor (HR) status, pathologic complete response (pCR) status, and biomarkers were analyzed. We confirmed the results of previously published reviews reporting residual cancer burden >0, non-pCR, and fewer tumor-infiltrating lymphocytes (TILs) as risk factors of recurrence. HR status remained an important risk factor for recurrence, with HER2+/HR+ disease more likely to recur. Two or more positive lymph nodes, higher BMI, larger primary tumor size, and low Ki67 were more commonly associated with HER2+ EBC recurrence. The identification of patient and disease factors frequently associated with HER2+ EBC recurrence in the literature provides insight into potential recurrence risk factors. Further investigation into the risk factors identified in this review could lead to improved treatments for patients at high risk for HER2+ EBC recurrence.