Abstract Background: According to recent EANO-ESMO guidelines, proactive brain imaging can be considered in asymptomatic patients (pts) with HER2+ metastatic breast cancer (mBC), due to high risk of developing brain metastases (BMs), with the aim of detecting brain involvement before the development of impactful symptoms. However, no clear evidence to guide the use of a specific radiological technique and timing for brain screening is currently available. After changes in EANO-ESMO guidelines, several oncologists in Italy have started to pragmatically include brain evaluation in CE CT scans performed to re-evaluate HER2+ mBC (traditionally only including thorax/abdomen). However, we lack data regarding the potential impact of this strategy in reducing the frequency of symptomatic BM diagnosis. We here retrospectively assess the impact of brain screening using CE CT scans on incidence of symptomatic BMs in HER2+ mBC pts. Methods: All consecutive pts newly diagnosed with HER2+ mBC and treated with trastuzumab-pertuzumab plus taxane at a single center (2014-2024) were retrospectively identified. Pts with symptomatic BMs at first mBC diagnosis or lacking complete imaging data regarding the first 2 years from mBC diagnosis were excluded. Pts were classified as having undergone brain screening if at least one CE brain CT scan per year was performed in absence of neurological symptoms during the first 2 years following mBC diagnosis, by clinical practice of treating oncologist. Results: Overall, 148 pts were identified: 73 underwent brain screening during the 2-year observation period and 75 did not. Both subgroups represented similar clinicopathological features at mBC diagnosis, including Karnofsky Performance Status (KPS). As expected, patients who underwent brain screening were diagnosed more recently and had a significantly shorter median follow-up from mBC diagnosis (3.0 versus 5.9 years, p0.001). Median number of brain CT scans per year in asymptomatic pts (during the first 2 years) was 2.0 (IQR 1.2-2.5) and 0.0 (IQR 0.0-0.5) in the screening and non-screening groups, respectively. Thirty pts (20.3%) developed BMs during the first 2 years. Cumulative incidence of BMs at 2-years was significantly higher in pts undergoing screening (vs not) (30.6% vs 12.3%, Gray’s p=0.004). However, cumulative incidence of symptomatic BMs at 2-years was significantly lower in pts undergoing screening (vs not) (0% vs 9.5%, Gray’s p=0.012). Moreover, pts undergoing screening presented a significantly more conserved performance status (KPS 90-100 for 71.4% of pts vs 11.1%, respectively; p=0.002) and a numerical trend toward a lower number of BMs at BM diagnosis (52.4% diagnosed with 3 BMs vs 88.9%, p=0.057). No significant difference in locoregional and systemic treatments administered after BM diagnosis was observed, although whole-brain radiotherapy (WBRT) was less frequently used in pts undergoing screening (14.3% vs 44.4%, p=0.073). Median OS from BM diagnosis was numerically longer in pts undergoing screening (28.6 vs 7.5 months, p=0.192). Conclusions: Brain screening with CT scans is associated with a significantly lower incidence of symptomatic BMs and with a significantly more conserved KPS at BM diagnosis in this retrospective real-world cohort of HER2+ mBC pts treated with pertuzumab-trastuzumab and taxane. These findings support the use of proactive brain imaging for pts with HER2+ mBC. Confirmatory prospective studies are needed to optimize surveillance timing and radiological techniques in this setting. Citation Format: G. Griguolo, M. Bottosso, G. Landa, G. Bonomi, F. Miglietta, M. Guarascio, M. La Commare, F. Zanghì, C. Giorgi, C. Falci, C. Hodgdon, M. Dieci, V. Guarneri. Proactive Brain Screening using contrast-enhanced (CE) brain CT scans in HER2+ metastatic Breast Cancer (mBC) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-09.
Griguolo et al. (Tue,) studied this question.