Abstract 4499
Background
Several lines of evidence suggest the involvement of CCND1 and FGFR1 genes in determining breast cancer (BC) resistance to endocrine therapy, however these assumptions still require a validation in clinical data sets.
Methods
This study included 138 tumors from patients with metastatic BC who received first-line endocrine therapy with aromatase inhibitors (AI, n = 69), tamoxifen (n = 65), goserelin (n = 2) or a combination of goserelin and tamoxifen (n = 2). DNA extracted from formalin-fixed paraffin-embedded archival specimens was tested for CCND1 and FGFR1 amplification by digital droplet PCR.
Results
CCND1 and FGFR1 status was successfully determined in 134 tumors. CCND1 and FGFR1 amplification was detected in 24 (18%) and 28 (21%) informative cases, respectively; 9 carcinomas had concurrent alterations of two genes. Amplifications were more common in less differentiated tumors (G1: 1/18 (6%) vs. G2-3: 34/86 (40%); p = 0.005, Fisher’s exact test). Median disease-free survival in patients receiving AI with CCND1 amplification was shorter than in cases with the normal gene status (12.3 vs. 14.9 months; p = 0.014, log rank test). Objective response to aromatase inhibitors was observed in 2/13 (15%) BC with FGFR1 amplification compared to 22/46 (48%) tumors with the normal FGFR1 gene copy number (p = 0.054). Noteworthy, among patients receiving AI, CCND1 and/or FGFR1 amplification occurred in 5 out of 7 (71%) women with progressive disease compared to only 4 in 23 (17%) patients with objective response to therapy (p = 0.01). Meanwhile, none of 5 tumors showing resistance to tamoxifen harbored CCND1 or FGFR1 amplification.
Conclusions
The presence of CCND1 and/or FGFR1 amplification is associated with worse results of AI therapy in breast cancer patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Russian Foundation for Basic Research (grant 17-04-01281).
Disclosure
All authors have declared no conflicts of interest.
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