Abstract
PurposeVarious aberrations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 are found in different cancers, including breast cancer (BC). This study analyzed the impact of FGFR amplification on the BC prognosis.MethodsThe study included 894 BC patients. The amplification rates of FGFR1, FGFR2, and FGFR3 were evaluated on tissue microarrays using fluorescence in situ hybridization (FISH). Associations between these parameters and prognosis were analyzed using multivariate Cox regression analyses.ResultsFGFR1 FISH was assessable in 503 samples, FGFR2 FISH in 447, and FGFR3 FISH in 562. The FGFR1 amplification rate was 6.6% (n = 33). Increased FGFR2 copy numbers were seen in 0.9% (n = 4); only one patient had FGFR3 amplification (0.2%). Most patients with FGFR1 amplification had luminal B-like tumors (69.7%, n = 23); only 32.6% (n = 153) of patients without FGFR1 amplification had luminal B-like BC. Other patient and tumor characteristics appeared similar between these two groups. Observed outcome differences between BC patients with and without FGFR1 amplification did not achieve statistical significance; however, there was a trend toward poorer distant metastasis-free survival in BC patients with FGFR1 amplification (HR = 2.08; 95% CI 0.98 to 4.39, P = 0.05).ConclusionFGFR1 amplification occurs most frequently in patients with luminal B-like BC. The study showed a nonsignificant correlation with the prognosis, probably due to the small sample size. Further research is therefore needed to address the role of FGFR1 amplifications in early BC patients. FGFR2 and FGFR3 amplifications are rare in patients with primary BC.
Highlights
Breast cancer (BC) is the most common malignant tumor in women [17]
Breast cancer cell lines with FGFR1 amplification harbor endocrine resistance that can be reversed by RNA silencing, and FGFR1-amplified breast cancers have been reported to be associated with a poorer prognosis [13]
This study investigated the amplification rates of the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 in patients with breast cancer
Summary
Breast cancer (BC) is the most common malignant tumor in women [17]. Treatment decisions in breast cancer patients are based on tumor predictive markers [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)], some of which are prognostic markers (ER, PR, HER2, Ki-67).The prognostic and predictive values of many different biomarkers in relation to breast cancer have been evaluated in recent years. In the era of personalized medicine, more and more genetic aberrations in potentially targetable oncogenic driver genes, such as copy number variations of CCND1 and PIK3CA mutations, are being investigated [9, 40]. Another promising biomarker in breast cancer is the fibroblast growth factor receptor 1 gene (FGFR1, chromosomal region: 8p11.2-p12). Amplification of FGFR1 is found in several types of cancer (e.g., nonsmall cell lung carcinoma, head and neck tumors, breast cancer, ovarian cancer, bladder cancer, and rhabdomyosarcoma) [10, 11, 22, 38, 52], with a frequency of up to 10% in breast cancer [61]. Breast cancer cell lines with FGFR1 amplification harbor endocrine resistance that can be reversed by RNA silencing, and FGFR1-amplified breast cancers have been reported to be associated with a poorer prognosis [13]
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