A multicentre retrospective study concludes that molecular analysis of brain metastases helps select systemic treatment options for a substantial share of patients. When the molecular profile of the metastasis was used to guide treatment, therapy was adjusted in 13%-27% of cases, depending on the primary tumour.
What was known
Brain metastases require a multidisciplinary approach combining surgery, radiotherapy and systemic therapy. Guidelines recommend testing established cancer driver genes in the metastatic tissue, but little is known about how this is applied in real-world practice and how far it influences treatment decisions. In breast cancer, the markers analysed are HER2, oestrogen and progesterone receptors, and BRCA1/2.
What this work adds
This multicentre retrospective study reviewed patients operated on for brain metastases from melanoma, lung cancer and breast cancer between 2010 and 2022. The authors examined clinical records for molecular analyses of predefined driver genes (ALK, BRAF, EGFR, KRAS and NTRK in lung; HER2, hormone receptors and BRCA1/2 in breast; BRAF, KIT and NRAS, among others, in melanoma), their discordance with the extracranial tumour, and whether systemic therapy was adjusted on the basis of that profile.
Main results
Of 1,431 brain metastases screened, molecular profiling was performed at least partially in 723 (51%). Among 276 cases with a matched extracranial tumour sample, discordant alterations were found in 18% of lung, 4.7% of melanoma and 45% of breast cancer metastases. Molecular profiling of the metastasis prompted adjustments to systemic therapy in 13%-27% of patients, depending on the primary tumour. Overall survival was significantly better in those who underwent profiling, especially among patients operated on in recent years (median 19.3 vs. 9.9 months; p < 0.0001) and in breast cancer patients whose systemic therapy changed after profiling (p = 0.0085).
What it means
The work supports the idea that molecular profiling of brain metastases is not an academic exercise: in a relevant subset of patients it opens the door to targeted treatments that would not have been considered based on the original tumour. The authors themselves stress the need for more systematic molecular testing in these patients to guide treatment decisions. As a retrospective, observational study, the results do not prove causality.
A view from the breast unit
The high discordance seen in breast cancer (45%) reinforces the value of biopsying and analysing the brain metastasis rather than assuming the profile of the primary tumour. In practice, this requires coordination between the breast unit, neurosurgery and pathology to ensure the available tissue is studied with an appropriate panel.
Reference: Nikolaeva M, Bellomo J, Gönel M, Stumpo V, Staartjes VE, Vasella F, et al. Clinical Implementation and Oncological Relevance of Molecular Profiling in Brain Metastases Patients-A Multicenter Retrospective Cohort Study. International Journal of Cancer, 2026. doi:10.1002/ijc.70611
