Abstract P2-10-10: The associations between brain metastasis and tumor size, nodal status, and patterns of extracranial metastasis vary by subtypes in breast cancer patients: A population-based study
Authors: Shen Bo , Li Jieqing , Yang Mei , Zhang Junsheng , Li Weiping , Wang Kun 
Published: March 2022

Abstract
Background: Brain metastasis (BM) was traditionally considered to occur in the terminal stage of breast cancer (BC) and be associated with large tumor size and nodal involvement. However, evidence suggests in triple-negative BC patients, the effects of T stage and N stage on the risk of BM were not prominent. Besides, recent studies have identified some overlap in gene expression profiles between brain and lung metastasis, but further validation in clinical settings is lacking. Therefore, one objective of our study was to determine the risk factors associated with BM in BC patients on a population-based level, focusing on the relationship between extracranial metastasis and BM. We also intended to investigate whether the associations differ across different strata by evaluating the interactions among risk factors of BM. Methods: The Surveillance, Epidemiology, and End Results database was used to select BC patients diagnosed from 2010 to 2018. We calculated the incidence proportions of BM and performed univariate and multivariate logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CI) for analyses of potential risk factors of BM. Interactive effects of any suspected risk factors were evaluated using a multiplicative interaction term and adjusting for all covariates. After the statistical interactions were found, we performed stratified analyses to further test the relationships between two risk factors. Results: A total of 527,525 BC patients were selected. For patients with only one extracranial metastatic site, lung was the most common metastatic site (6.37%), followed by bone (4.12%) and liver (3.42%). Multivariate logistic regression analysis among the whole population showed age, subtype, grade, T stage, N stage, histology, and pattern of extracranial metastasis are independent predictors of BM, while sex, race, and laterality did not significantly influence risks of BM. We found significant interactions between subtype and T stage (p = 0.004) and between subtype and N stage (p = 0.002) that increased the risk of BM. In stratified analyses, the associations of BM with T stage were significant in all subtypes except HR-/HER2- (Table 1). Only in HR+/HER2+ and HR-/HER2- patients, the associations of N stage with BM were significant (p &lt; 0.001 for both groups). The associations of T stage and N stage with BM did not differ by age. For patients with only one extracranial metastatic site, pattern of extracranial metastasis significantly interacted with subtype (p = 0.013). The association of extracranial metastatic pattern with BM was significant only among HR-/HER2- patients. Compared to patients with extracranial metastasis only to the bone, patients with extracranial metastasis only to the liver had a lower risk of BM (OR = 0.455, 95% CI: 0.219-0.948, p = 0.035), while patients with extracranial metastasis only to the lung had a higher risk of BM (OR = 1.936, 95% CI: 1.300-2.882, p = 0.001). Conclusion: Breast subtypes can modify the associations of BM with tumor size, nodal status, and pattern of extracranial metastasis. Risk elevations with higher T stage are significant among all subtypes except HR-/HER2-, indicating BM in HR-/HER2- patients may not be driven by larger tumor size. HR-/HER2- patients with lung metastasis are more susceptible to BM, providing clinical evidence for pathway overlap between brain and lung metastases.
Table 1.Stratified associations between T stage and brain metastasismultivariable-adjusted OR (95% CI)p for trendp for interactionT1T2T3T4T-unknownSubtype0.004HR+/HER2-Reference1.550 (1.221-1.968)1.641 (1.227-2.194)1.816 (1.399-2.358)2.097 (1.575-2.793)&lt; 0.001HR+/HER2+Reference0.979 (0.660-1.452)1.185 (0.741-1.894)1.605 (1.065-2.418)1.686 (1.048-2.712)0.009HR-/HER2+Reference1.410 (0.862-2.305)1.187 (0.658-2.141)1.733 (1.050-2.858)3.489 (2.030-5.998)&lt; 0.001HR-/HER2-Reference0.993 (0.701-1.407)1.300 (0.863-1.958)1.402 (0.959-2.052)1.499 (0.940-2.388)0.126
Citation Format: Bo Shen, Jieqing Li, Mei Yang, Junsheng Zhang, Weiping Li, Kun Wang. The associations between brain metastasis and tumor size, nodal status, and patterns of extracranial metastasis vary by subtypes in breast cancer patients: A population-based study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-10.