Locoregional Recurrence Patterns in Patients With Different Molecular Subtypes of Breast Cancer

Abstract

While numerous studies have consistently reported that the molecular subtypes of breast cancer (BC) are associated with different patterns of distant metastasis, few studies have investigated the association of tumor subtypes with locoregional recurrence. To investigate the patterns of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), and contralateral BC (CBC) according to tumor subtypes. This retrospective cohort study used the clinical records of patients who underwent BC surgery at a single institution in South Korea between January 2000 and December 2018. Data were analyzed from May 1, 2019, to February 20, 2023. Ipsilateral breast tumor recurrence, RR, and CBC events. The primary outcome was differences in annual incidence patterns of IBTR, RR, and CBC according to tumor subtypes. Hormone receptor (HR) status was assessed by immunohistochemical staining assay, and ERBB2 status was evaluated according to American Society of Clinical Oncology and College of American Pathologists guidelines. A total of 16 462 female patients were included in the analysis (median age at time of operation, 49.0 years [IQR, 43.0-57.0 years]). The 10-year IBTR-, RR-, and CBC-free survival rates were 95.9%, 96.1%, and 96.5%, respectively. On univariate analysis, HR-/ERBB2+ tumors had the worst IBTR-free survival (vs HR+/ERBB2- subtype: adjusted hazard ratio, 2.95; 95% CI, 2.15-4.06), while the HR-/ERBB2- subtype had the worst RR- and CBC-free survival among all subtypes (vs HR+/ERBB2- subtype, RR: adjusted hazard ratio, 2.95; 95% CI, 2.37-3.67; CBC: adjusted hazard ratio, 2.12; 95% CI, 1.64-2.75). Subtype remained significantly associated with recurrence events in Cox proportional hazards regression analysis. Regarding the annual recurrence pattern, the IBTR patterns of HR-/ERBB2+ and HR-/ERBB2- subtypes showed double peaks, while HR+/ERBB2- tumors showed a steadily increasing pattern without distinguishable peaks. Additionally, the HR+/ERBB2- subtype seemed to have a steady RR pattern, but other subtypes showed the highest RR incidence at 1 year following surgery, which then gradually decreased. The annual recurrence incidence of CBC gradually increased among all subtypes, and patients with the HR-/ERBB2- subtype had a higher incidence than patients with other subtypes over 10 years. Younger patients (age ≤40 years) had greater differences in IBTR, RR, and CBC patterns between subtypes than did older patients. In this study, locoregional recurrence occurred with different patterns according to BC subtypes, with younger patients having greater differences in patterns among subtypes than older patients. The findings suggest that tailoring surveillance should be recommended regarding differences in locoregional recurrence patterns according to tumor subtypes, particularly for younger patients.