Abstract 5793: Comprehensive characterization of FGF/FGFR alterations in invasive breast cancers
Authors: Gaur Kush C. , Tiu-Lim Justin , McGrath Julie , Walker Phil , Korn Michael , Xiu Joanne , Heeke Arielle , Kaklamani Virginia , Tan Antoinette , Lu Janice , Spicer Darcy , Roussos-Torres Evanthia , Jayachandran Priya , Saghian Audrey , Goldkorn Amir , Kang Irene 
Published: June 2022

Abstract
BACKGROUND FGFR signaling is central for cancer cell proliferation, migration, angiogenesis, and survival. The frequency and type of FGF/FGFR aberrations are not well-characterized across invasive breast cancer subtypes and metastatic sites of disease. In hormone receptor positive breast cancers, FGFR1 amplification correlates with early progression on endocrine therapy and promotes resistance to CDK4/6 inhibition. Our study evaluated the incidence and characterization of FGF alterations in invasive breast cancers and examined differences based on histologic subtype, molecular subtype and site.
METHODS Breast cancer samples underwent molecular profiling by Caris Life Sciences. Analyses included NGS of DNA (592 Gene Panel, NextSeq, and WES, NovaSEQ), and IHC (Caris Life Sciences, Phoenix, AZ). Biomarker results were compiled from cases within the breast cohort including data from any sequencing panel, gene expression/RNA seq panel, and IHC. All results listed below were statistically significant (p &lt; 0.05) as determined by chi-square test and Benjamini Hochberg correction.
RESULTS 12058 breast cancer tumors were analyzed: 4189 from primary breast specimens (35%) and 7869 from metastatic sites (65%). 4305 (36%) were ductal and 671 (6%) were lobular histology with remaining other/unknown. 6413 (53%) were HR+HER2-, 3504 (29%) were triple negative, 403 (3%) were HR+HER2+ and 363 (3%) were HR-HER2+ with 1375 (13%) of unknown subtype. In the entire cohort, the most commonly amplified genes were FGF19 (11.49%), FGF3 (10.75%), FGF4 (9.98%), CCND1 (12.36%), and FGFR1 (9.08%). FGFR1-4 amplification was present in 11.01% of all cases. FGF19 amplification was more prevalent in lobular breast cancer compared to ductal (12.1% vs 9.1%). FGF19, FGF23, FGF3, FGF4, FGF6 amplification varied across molecular subtypes being most prevalent in HR+/HER2- (15.7%), HR+/HER2+ (12.1%), and least prevalent in HR-/HER+ tumors (3.4%). FGFR1 amplification was most common among FGFR1-4 amplifications and most prevalent in HR+HER2- (12%). Across metastatic sites, FGF ligands displayed different patterns of amplification with FGF19, FGF3 and FGF4 amplification most prevalent in liver and bone metastases. FGFR1 amplification was statistically different across metastatic sites and most prevalent in liver metastases (16%) followed by bone (10%). Patients receiving CDK4/6 inhibitors with FGFR1 amplification had shorter time on treatment than FGFR1 wild type (HR = 0.892, p = 0.03).
CONCLUSION FGF alterations in invasive breast cancers vary by molecular subtype and site of disease. FGFR1, FGF19, FGF23, FGF3, FGF4, and FGF6 amplifications were statistically different across subtypes (most prevalent in HR+/HER2- and HR+/HER2+) and metastatic sites (most prevalent in liver and bone metastases). The prevalence in HR+ subtypes lend support to the role of FGF in endocrine resistance.
Citation Format: Kush C. Gaur, Justin Tiu-Lim, Julie McGrath, Phil Walker, Michael Korn, Joanne Xiu, Arielle Heeke, Virginia Kaklamani, Antoinette Tan, Janice Lu, Darcy Spicer, Evanthia Roussos-Torres, Priya Jayachandran, Audrey Saghian, Amir Goldkorn, Irene Kang. Comprehensive characterization of FGF/FGFR alterations in invasive breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5793.