Lundberg, A., Lindström, L.S., Li, J. et al. The long-term prognostic and predictive capacity of cyclin D1 gene amplification in 2305 breast tumours. Breast Cancer Res 21, 34 (2019). https://doi.org/10.1186/s13058-019-1121-4
Abstract:
Background:
Use of cyclin D1 (CCND1) gene amplification as a breast cancer biomarker has been hampered by conflicting assessments of the relationship between cyclin D1 protein levels and patient survival. Here, we aimed to clarify its prognostic and treatment predictive potential through comprehensive long-term survival analyses.
Methods:
CCND1 amplification was assessed using SNP arrays from two cohorts of 1965 and 340 patients with matching gene expression array and clinical follow-up data of over 15 years. Kaplan-Meier and multivariable Cox regression analyses were used to determine survival differences between CCND1 amplified vs. non-amplified tumours in clinically relevant patient sets, within PAM50 subtypes and within treatment-specific subgroups. Boxplots and differential gene expression analyses were performed to assess differences between amplified vs. non-amplified tumours within PAM50 subtypes.
Results:
When combining both cohorts, worse survival was found for patients with CCND1-amplified tumours in luminal A (HR = 1.68; 95% CI, 1.15–2.46), luminal B (1.37; 1.01–1.86) and ER+/LN−/HER2− (1.66; 1.14–2.41) subgroups. In gene expression analysis, CCND1-amplified luminal A tumours showed increased proliferation (P
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This work was supported by the Iris, Stig och Gerry Castenbäcks Stiftelse for cancer research (to N.P.T), the King Gustaf V Jubilee Foundation (to N.P.T and J.B.), BRECT, the Swedish Cancer Society, the Cancer Society in Stockholm Personalised Cancer Medicine (PCM), the Swedish Breast Cancer Association (BRO) and the Swedish Research Council (to JB), and by the Swedish Research Council (grant no: 521–2014- 2057; to L.S.L). C.M.P and J.C.H were supported by funds from the NCI Breast SPORE program (P50-CA58223-09A1), by R01- CA195754–01, and the Breast Cancer Research Foundation (to C.M.P). JL was supported by a National Research Foundation Singapore Fellowship (NRF-NRFF2017–02).