Sequential Anti-HER2 (Human Epidermal Growth Factor Receptor 2) Therapy and Late-Line Tucatinib in Patients With HER2-Positive Breast Cancer and Brain Metastases: A Real-World Case Report

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with a high incidence of brain metastases (BMs), particularly among young and heavily pretreated patients, with intracranial disease remaining a major determinant of survival and quality of life (QoL).Tucatinib, a HER2-selective tyrosine kinase inhibitor (TKI), combined with trastuzumab and capecitabine, has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit, including in patients with active BMs.We present the case reports of two patients, both younger than 50 years, with HER2-positive metastatic breast cancer and biologically aggressive disease who progressed on prior anti-HER2 therapy (trastuzumab, lapatinib, and ado-trastuzumab emtansine (Ujvira™) in Case 1 and trastuzumab in Case 2) with worsening central nervous system involvement.Both were subsequently treated with tucatinib-based combination therapy (Tukavo™) later in the treatment sequence, once it became available and affordable, and showed clinical and radiological improvement.Case 1 had improvement in right-sided limb weakness and speech with no further seizures and remained clinically stable for seven months, and Case 2 had complete resolution of headache and vomiting, with Eastern Cooperative Oncology Group (ECOG) performance status improving from 2 to 1. QoL was assessed clinically from symptoms and performance status rather than with a validated instrument.This real-world experience illustrates the potential benefit of tucatinib-based regimens in young patients with aggressive HER2-positive breast cancer and BMs, even when used later in the treatment sequence.These findings are consistent with pivotal trial data in a resource-limited, realworld setting.