Abstract
Simple SummaryBrain metastases (BM) may affect a large portion of metastatic HER2-positive BC patients. Dual human epidermal growth factor receptor 2 (HER2) blockade with Pertuzumab and Trastuzumab (PT) in conjunction with chemotherapy represents the first line therapy of metastatic HER2- positive breast cancer (BC) and shows to prolong time to BM development as the first site of disease progression. When limited brain disease occurs with stable extracranial disease, current guidelines suggest to continue systemic therapies and add local brain treatment. However not data are available on the association between PT and stereotactic brain radiotherapy (SRT). This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and PT in patients with breast cancer BM.(1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.
Highlights
In HER2-positive breast cancer (BC) metastatic patients, it is estimated that more than30% of patients will develop brain metastases (BM)
This is a retrospective study aimed at assessing the safety and efficacy of fractionated SRT (fSRT) and double blockade HER2 with pertuzumab and trastuzumab in patients with breast cancer brain metastases (BCBM), performed in accordance with the Declaration of Helsinki
A total of 10 patients (20.4%) with 32 HER2+ BCBM were treated with concurrent fSRT and PT
Summary
In HER2-positive breast cancer (BC) metastatic patients, it is estimated that more than. 30% of patients will develop brain metastases (BM). In the post-trastuzumab era, with patients experiencing longer survival due to increased extracranial disease control, the brain often represents the first site of relapse. The introduction of HER2targeted therapies improved the survival HER2 positive BC patients, including those with. Pertuzumab (P) is a humanized monoclonal antibody that is directed against extracellular domain 2 of HER2 receptor and inhibits the interaction of HER2 with HER3. To trastuzumab (T), P stimulates both antibody-dependent and cell-mediated cytotoxicity. In preclinical HER2 positive models, the T and P combination shows increased antitumor effect compared to either agent alone [6,7,8]
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