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William J. Gradishar, MD, FACP, FASCO


p-STAT3 Expression in Brain Metastases From Breast Cancer Subtypes: Impact on Clinical Outcomes

By: Angela Lorio
Posted: Tuesday, September 5, 2023

Alessia Pellerino, MD, PhD of the University and City of Health and Science Hospital, Turin, Italy, and colleagues, explored the potential impact on outcomes of expression of phosphorylated transducer and activator of transcription-3 (p-STAT3) in peritumoral reactive astrocytes of brain metastases in breast cancer subtypes. Specifically, p-STAT3 expression in these astrocytes of triple-negative and HER2-positive brain metastases was higher than in luminal brain metastases. In fact, earlier disease progression was noted in patients who had triple-negative brain metastases with high p-STAT3 expression. These results were presented at the 2023 joint Society for Neuro-Oncology/American Society of Clinical Oncology (SNO-ASCO) CNS Cancer Conference (Abstract BSBM-12).

Expression of p-STAT3 was high in 79.4% of triple-negative and 60.0% of HER2-positive brain metastasis, whereas most (83.3 %) luminal brain metastases had low or absent p-STAT3 expression. In terms of clinical outcomes, those with triple-negative brain metastases who had higher p-STAT3 expression experienced earlier disease progression than did those who had brain metastases with low expression of p-STAT3 (4 months vs. 20 months). Median intracranial disease progression was 16.0 months (range 7–80 months).

The University of Turin and the Spanish National Brain Metastasis Network (RENACER) investigators have now analyzed 105 specimens. Intracranial disease progression was measured according to p-STAT3 expression, which was scored as high (2 or 3), low (1), or absent (0). Approximately 30% of the specimens were of the luminal subtype, 33% were HER2-positive, and 37% were triple-negative brain metastases. Immunohistochemistry was feasible in 83.8 % (88 of 105). Of the 88 patients, 49 (55.7 %) showed positive staining for p-STAT3, of whom 56.6% scored high, 31.9% scored low, and 12.6% were absent.

Disclosure: The study authors reported no conflicts of interest.

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