Detection of  CCND1 ,  C-MYC , and  FGFR1  amplification using modified SYBR Green  qPCR and FISH in breast cancer

Azarnezhad, Asaad; Tabrizi, Mina; Javan, Firouzeh; Mehdipour, Parvin

doi:10.3906/sag-1710-93

Cited by 1 publication

(3 citation statements)

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“…This meta-analysis included 18 studies comprising 6400 patients. Of these, 1136 (18%) had CCND1 amplified tumours, which is within the 10-35% range generally reported (2)(3)(4). Previous evidence suggested an association between CCND1 amplification and ER positive status (4,13,15,51).…”

Section: Discussionmentioning

confidence: 53%

“…Interestingly, one study showed that cyclin D1 immunostaining with an Allred score of >6.5 (57) was predictive of CCND1 amplification in ER positive BCa patients, with high sensitivity (94.2%) and specificity (87.8%) (13). This is somewhat surprising, given that CCND1 amplification occurs in 10-35% of BCa tumours (Table 1), and cyclin D1 overexpression occurs in 50-70% of BCa tumours (2)(3)(4).…”

Section: Discussionmentioning

confidence: 99%

“…Cyclin D1, along with its binding partners cyclin dependent kinases (CDK4/6), is a key regulator of the cell cycle, mediating transition from G 1 to S phase (Figure 1). The gene encoding cyclin D1, CCND1, located on chromosome 11q13.3, has been reported to be amplified in 10-35% of breast cancers (BCa) (2)(3)(4) and its amplification has been associated with increased cyclin D1 expression (3). CCND1 amplification may be an effective prognostic and predictive biomarker in BCa.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis

et al. 2022

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BackgroundUp to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). CCND1 encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. CCND1 amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of CCND1 amplification on estrogen receptor positive patients’ disease outcomes, is vital. This review aims to evaluate CCND1 amplification as a prognostic and predictive biomarker in BCa.Materials and MethodsPublications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, in vitro and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35, CCND1 amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].ResultsCCND1 amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). CCND1 amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, CCND1 amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.ConclusionWhile a lack of standardised approach for the detection of CCND1 amplification is to be considered as a limitation, CCND1 amplification was found to be prognostic of shorter RFS and OS in BCa. CCND1 amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of CCND1 amplification, CCND1 amplification would have potential as a predictive biomarker in breast cancer patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.

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