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.
Resources from the same session
4732 - Progesterone Receptor Isoform Ratio Dictates Antiprogestins/Progestins Effects on Metastatic Breast Cancer Models
Presenter: Maria Abascal
Session: Poster Display session 2
Resources:
Abstract
5737 - PAM50 and CGH-array genomic characterization of HER2-Equivocal Breast Cancers defined by the 2018 ASCO/CAP recommendations.
Presenter: Carine Ngo
Session: Poster Display session 2
Resources:
Abstract
1096 - OncotypeDX® predictive nomogram for recurrence score output: a machine learning system based on quantitative immunochemistry analysis - ADAPTED01
Presenter: Fabio Marazzi
Session: Poster Display session 2
Resources:
Abstract
5426 - Geriatric parameters predict both disease-related and patient-reported outcomes in older patients with breast cancer
Presenter: Willeke van der Plas-Krijgsman
Session: Poster Display session 2
Resources:
Abstract
5865 - Patients with a 21-gene assay in South East London differ from the TAILORx trial population
Presenter: Charalampos Gousis
Session: Poster Display session 2
Resources:
Abstract
1312 - Predictive tools in adjuvant breast cancer – what is the standard of evidence supporting their utility? A literature review examining validation of Adjuvant!, Cancermath and NHS Predict
Presenter: Alice Loft
Session: Poster Display session 2
Resources:
Abstract
2445 - Oncologic outcome of invasive lobular carcinoma: Is it different from that of invasive ductal carcinoma?
Presenter: Hee Jun Choi
Session: Poster Display session 2
Resources:
Abstract
2476 - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer
Presenter: SERAFIN MORALES Murillo
Session: Poster Display session 2
Resources:
Abstract
3761 - Chemotherapy-induced amenorrhea: prognostic impact on premenopausal Egyptian patients with breast cancer
Presenter: Khaled Abdel Karim
Session: Poster Display session 2
Resources:
Abstract
4687 - Predicting the presence of breast cancer using circulating small RNA in the serum
Presenter: Yumiko Koi
Session: Poster Display session 2
Resources:
Abstract