Management of HER2+ Breast Cancer with and without Brain Metastases in Saudi Arabia: Literature Insights and an Expert Survey of Current Practices

Purpose: New therapies can improve outcomes in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC), including those with brain metastases (BMs). To our knowledge this is the first review focusing on HER2+ mBC, with and without BMs, in the Saudi Arabian context. This review evaluated the epidemiology of HER2+ mBC with and without BMs, treatment and monitoring practices in Saudi Arabia. Methods: Two key strategies have been pursued: a comprehensive literature review of international recommendations to complement a focused, nationally-representative cross-sectional survey involving BC experts in Saudi Arabia using an 18-item questionnaire. Results: Twelve expert BC physicians from tertiary treatment centers in Saudi Arabia completed the survey. It was estimated that 15– 35% of mBC patients present with HER2+ disease, with 5– 25% developing BMs. Internationally, brain imaging of asymptomatic patients is currently a subject of controversial debate; only 17% of surveyed physicians conducted brain imaging in asymptomatic patients. Treatment of HER2+ mBC with and without BMs in Saudi Arabia largely aligned with international recommendations identified in our literature analysis, although access to lapatinib, tucatinib and neratinib can be limited and may lead to use of alternative regimens. In third-line or later settings, tucatinib combinations were favored by physicians. Conclusion: The management of HER2+ mBC with and without BMs among expert physicians in Saudi Arabia is aligned with international guidelines. The tucatinib-combination may be considered the standard of care for adult patients with HER2+ locally advanced or mBC who have received at least two prior anti-HER2+ treatment regimens, including patients with BMs. Ensuring access to innovative HER2+ mBC therapies across Saudi Arabia is crucial to supporting best practice. Plain Language Summary: HER2‑positive metastatic breast cancer is a form of advanced breast cancer for which several modern treatments can improve outcomes, including for people whose cancer spreads to the brain. However, little is known about how these treatments are used in everyday practice in Saudi Arabia. In this study, we reviewed international guidelines and surveyed breast cancer specialists across Saudi Arabia to understand current approaches. We found that HER2‑positive disease accounts for around 15– 35% of metastatic breast cancer cases in Saudi Arabia, and 5– 25% of these individuals develop cancer in the brain. Most doctors only request brain scans when a person has symptoms, reflecting ongoing global debate about routine scanning in people who feel well. Overall, treatment choices in Saudi Arabia were very similar to international recommendations, although access to some newer HER2‑targeted medicines, such as lapatinib, tucatinib and neratinib, can still be limited in some centers. When people needed a third or later line of treatment, specialists most often favored tucatinib‑based combinations. These findings show that clinicians in Saudi Arabia largely follow global best practice in managing HER2‑positive metastatic breast cancer, including in people with cancer that has spread to the brain. Improving access to newer HER2‑targeted medicines could strengthen care further and ensure that individuals across the country benefit from the most effective treatments available. Keywords: breast, cancer, HER2+, metastatic, brain, metastases, Saudi Arabia