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
3716 - Prognostic factors for predicting early recurrence within the first year of surgery in pancreatic ductal adenocarcinoma
Presenter: Naru Kim
Session: Poster Display session 2
Resources:
Abstract
3947 - Integrated population pharmacokinetic modelling of liposomal irinotecan in patients with various tumour types, including untreated metastatic pancreatic cancer (mPC)
Presenter: Teresa Macarulla
Session: Poster Display session 2
Resources:
Abstract
2880 - Expression of long noncoding RNA and clinical outcomes of pancreatic cancer patients who received adjuvant chemotherapy by S-1 or GEM after curative resection.
Presenter: Mariko Kamiya
Session: Poster Display session 2
Resources:
Abstract
5029 - POLO: Time to treatment discontinuation and subsequent therapies following maintenance olaparib for patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract
4730 - Diagnostic Value of Digital Multiplexed Detection of Single Nucleotide Variants in Pancreatic Cancer Specimens Collected by Endoscopic Ultrasound Fine-Needle Aspiration
Presenter: Irina Cazacu
Session: Poster Display session 2
Resources:
Abstract
3303 - Phase I/II study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer
Presenter: Esther Pijnappel
Session: Poster Display session 2
Resources:
Abstract
2009 - Efficacy of platinum-containing chemotherapy and prognosis of pancreatic cancer patients with homologous recombination deficiency: meta-analysis of published clinical studies
Presenter: Elizeveta Polyanskaya
Session: Poster Display session 2
Resources:
Abstract
2164 - Plasmatic CXCL8 is a marker for TGFß-activated kinase 1 (TAK1) activation which may predict resistance to nanoliposomal irinotecan (nal-IRI) in gemcitabine-refractory pancreatic cancer (PC) patients
Presenter: Valeria Merz
Session: Poster Display session 2
Resources:
Abstract
2529 - A protein level signature of four selected genes associated with survival outcomes of patients with pancreatic ductal adenocarcinoma
Presenter: Jie Hua
Session: Poster Display session 2
Resources:
Abstract
4947 - Pre-treatment serum 25-hydroxyvitamin D levels and survival in a Danish cohort of patients with pancreatic cancer
Presenter: Louise Rasmussen
Session: Poster Display session 2
Resources:
Abstract