Abstract Background This study assessed immunohistochemical (IHC) discordance between primary breast cancer (BC) and brain metastases (BCBM) in a Brazilian population. While 20-40% of BC patients develop BCBM, particularly those with HER2-positive or triple-negative subtypes, phenotypic changes may occur during disease progression, driven by tumor heterogeneity and alterations in the tumor microenvironment (TME). Due to the limited availability of BCBM samples, data on IHC discordance remain scarce. Methods This retrospective cohort study included women who underwent neurosurgical resection for BCBM between January 2015 and December 2022 at the Brazilian National Cancer Institute (INCA). Clinical and pathological data were extracted from medical records. IHC markers ─ estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 ─ were assessed in BCBM samples and compared with the corresponding archival primary breast cancer specimens. An alluvial diagram was used to visually represent patterns of IHC discordance. The primary objective was to describe the frequency of IHC discordance between primary BC and corresponding BCBM. Secondary objectives included evaluation of associations between clinicopathological and sociodemographic features and IHC discordance, as well as its impact on survival outcomes. Results Among the 105 eligible patients, 64% (n = 67 patients) were Black or mixed-race, and 41% (n = 42) had not completed primary education. A significant proportion were obese (43%, n = 45), and 42% (n = 44) had hypertension. The mean age was 49 years (SD ±10), and 58% (n = 61) were premenopausal. Most tumors were ductal (87%, n = 92), and grade II (45%, n = 47) or grade III (46%, n = 48), with the HER2-positive subtype being the most frequent (48%, n = 51). Overall, 69% (n = 52) of patients had locally advanced disease, with a mean of 5 (SD ±6) affected lymph nodes. Among those who received neoadjuvant chemotherapy, 16% (n = 13) achieved a pathological complete response. About 14% (n = 15) presented with de novo metastatic disease. At the time of BCBM diagnosis, 91% (n = 95) exhibited neurological symptoms, most commonly headache (62%, n = 59) and dizziness (37%, n = 35). A single brain lesion was observed in 67% (n = 70) of cases. IHC discordance between primary BC and BCBM was found in 44% (n = 46) of patients, but this was not associated with differences in survival outcomes, including overall survival (OS) (p = 0.96), recurrence-free survival after BCBM diagnosis (post-BCBM RFS) (p = 0.81), or OS after BCBM diagnosis (post-BCBM OS) (p = 0.53). The most common phenotypic changes were loss of ER/PR expression (76%, n = 35) and enrichment of HER2 expression (15%, n = 7). Loss of ER/PR expression was not associated with post-BCBM risk of death (p = 0.52). Conclusion A notably high frequency of IHC discordance between primary breast tumors and brain metastases was observed in this real-world Brazilian study, exceeding rates previously reported in the literature. To our knowledge, this is the first Brazilian study to investigate IHC changes in this context, conducted in a population with a high proportion of Black and mixed-race individuals. These results underscore the biological heterogeneity of breast cancer in underrepresented populations and emphasize the need for more precise, individualized management strategies for patients with BCBM. Citation Format: G. Carvalho, F. Rodrigues, P. Fernandes, I. Small, J. Silva, L. Araujo. Real-world evidence of immunohistochemical discordance in breast cancer brain metastases 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 PS2-04-02.
Carvalho et al. (Tue,) studied this question.