Real-World Evidence of Immunohistochemical Discordance in Breast Cancer Brain Metastases

Breast cancer brain metastases (BCBM) occur in 20-40% of patients with advanced breast cancer (BC), mainly in HER2-positive and triple-negative subtypes. Phenotypic shifts may arise, driven by alterations in the tumor microenvironment. However, due to the limited availability of BCBM specimens, data on immunohistochemical (IHC) discordance at this site remains scarce. This study aimed to determine the frequency of IHC discordance between primary BC and paired BCBM.

This retrospective study included women who underwent neurosurgical resection for BCBM between January 2015 and December 2022 at the Brazilian National Cancer Institute (INCA). IHC markers - ER, PR, HER2, and Ki67 - were assessed in BCBM samples and compared with the corresponding archival of primary BC specimens. A descriptive analysis was primarily conducted to determine the frequency of IHC discordance, followed by survival analyses.

Among the 105 eligible patient-cases, 33 (32%) were HR⁺/HER2^-, 35 (33%) HR⁺/HER2⁺, 16 (15%) HR^-/HER2⁺, and 19 (18%) triple-negative. IHC discordance between primary BC and BCBM was found in 46 (44%) patients. The most common phenotypic changes were loss of ER/PR expression (35, 76%) and enrichment of HER2 expression (7, 15%). IHC profile change was not associated with differences in survival outcomes, including progression-free survival after BCBM diagnosis (p = 0.81), overall survival (OS) (p = 0.96), or OS after BCBM diagnosis (p = 0.53).

A notably high frequency of IHC discordance between primary BC and BCBM was observed, exceeding rates previously reported. Recognizing this heterogeneity may guide more personalized treatment approaches.