Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis
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...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.895729/full |
| _version_ | 1828329697698643968 |
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| author | Sarah A. Jeffreys Sarah A. Jeffreys Therese M. Becker Therese M. Becker Sarah Khan Patsy Soon Patsy Soon Patsy Soon Hans Neubauer Paul de Souza Paul de Souza Paul de Souza Branka Powter |
| author_facet | Sarah A. Jeffreys Sarah A. Jeffreys Therese M. Becker Therese M. Becker Sarah Khan Patsy Soon Patsy Soon Patsy Soon Hans Neubauer Paul de Souza Paul de Souza Paul de Souza Branka Powter |
| author_sort | Sarah A. Jeffreys |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:29:17Z |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T20:29:17Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-38ad87533aa74a16b72faaaecd6ad7b32022-12-22T02:31:13ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.895729895729Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-AnalysisSarah A. Jeffreys0Sarah A. Jeffreys1Therese M. Becker2Therese M. Becker3Sarah Khan4Patsy Soon5Patsy Soon6Patsy Soon7Hans Neubauer8Paul de Souza9Paul de Souza10Paul de Souza11Branka Powter12Centre of Circulating Tumour Cell Diagnostics and Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaCentre of Circulating Tumour Cell Diagnostics and Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, AustraliaSouth Western Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, AustraliaDepartment of Medical Oncology, Bankstown Cancer Centre, Bankstown, NSW, AustraliaCentre of Circulating Tumour Cell Diagnostics and Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, AustraliaSouth Western Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, AustraliaDepartment of Surgery, Bankstown Hospital, Bankstown, NSW, AustraliaDepartment of Obstetrics and Gynaecology, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyCentre of Circulating Tumour Cell Diagnostics and Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSouth Western Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW, AustraliaCentre of Circulating Tumour Cell Diagnostics and Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, AustraliaBackgroundUp 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.895729/fullbreast cancerCCND1cyclin D1biomarkermeta-analysissystematic review |
| spellingShingle | Sarah A. Jeffreys Sarah A. Jeffreys Therese M. Becker Therese M. Becker Sarah Khan Patsy Soon Patsy Soon Patsy Soon Hans Neubauer Paul de Souza Paul de Souza Paul de Souza Branka Powter Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis Frontiers in Endocrinology breast cancer CCND1 cyclin D1 biomarker meta-analysis systematic review |
| title | Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis |
| title_full | Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis |
| title_fullStr | Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis |
| title_short | Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis |
| title_sort | prognostic and predictive value of ccnd1 cyclin d1 amplification in breast cancer with a focus on postmenopausal patients a systematic review and meta analysis |
| topic | breast cancer CCND1 cyclin D1 biomarker meta-analysis systematic review |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.895729/full |
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