Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review

Tim C. de Ruijter; Frank van der Heide; Kim M. Smits; Maureen J. Aarts; Manon van Engeland; Vivianne C. G. Heijnen

doi:10.1186/s13058-020-1250-9

Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review

Tim C. de Ruijter, Frank van der Heide, Kim M. Smits, Maureen J. Aarts, Manon van Engeland, Vivianne C. G. Heijnen^*

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Background: In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice.

Methods: We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies.

Results: A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study.

Conclusion: This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.

Original language	English
Article number	13
Number of pages	12
Journal	Breast Cancer Research
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s13058-020-1250-9
Publication status	Published - 31 Jan 2020

Keywords

Biomarkers
DNA methylation
Breast cancer
Hormone receptor positive
Oestrogen receptor positive
Luminal breast cancer
Prognosis
Promoter CpG island methylation
Survival
BRCA1 PROMOTER METHYLATION
POPULATION-BASED VALIDATION
DISEASE-FREE SURVIVAL
POOR-PROGNOSIS
CLINICAL-SIGNIFICANCE
SERUM DNA
POTENTIAL BIOMARKER
RASSF1A METHYLATION
ENDOCRINE THERAPY
MULTIPLE GENES

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Cite this

@article{b7034b067d6e41d88ae1fafbe6e4143b,

title = "Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review",

abstract = "Background: In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice.Methods: We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies.Results: A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study.Conclusion: This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.",

keywords = "Biomarkers, DNA methylation, Breast cancer, Hormone receptor positive, Oestrogen receptor positive, Luminal breast cancer, Prognosis, Promoter CpG island methylation, Survival, BRCA1 PROMOTER METHYLATION, POPULATION-BASED VALIDATION, DISEASE-FREE SURVIVAL, POOR-PROGNOSIS, CLINICAL-SIGNIFICANCE, SERUM DNA, POTENTIAL BIOMARKER, RASSF1A METHYLATION, ENDOCRINE THERAPY, MULTIPLE GENES",

author = "{de Ruijter}, {Tim C.} and {van der Heide}, Frank and Smits, {Kim M.} and Aarts, {Maureen J.} and {van Engeland}, Manon and Heijnen, {Vivianne C. G.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = jan,

day = "31",

doi = "10.1186/s13058-020-1250-9",

language = "English",

volume = "22",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd",

number = "1",

}

TY - JOUR

T1 - Prognostic DNA methylation markers for hormone receptor breast cancer

T2 - a systematic review

AU - de Ruijter, Tim C.

AU - van der Heide, Frank

AU - Smits, Kim M.

AU - Aarts, Maureen J.

AU - van Engeland, Manon

AU - Heijnen, Vivianne C. G.

PY - 2020/1/31

Y1 - 2020/1/31

N2 - Background: In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice.Methods: We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies.Results: A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study.Conclusion: This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.

AB - Background: In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice.Methods: We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies.Results: A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study.Conclusion: This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.

KW - Biomarkers

KW - DNA methylation

KW - Breast cancer

KW - Hormone receptor positive

KW - Oestrogen receptor positive

KW - Luminal breast cancer

KW - Prognosis

KW - Promoter CpG island methylation

KW - Survival

KW - BRCA1 PROMOTER METHYLATION

KW - POPULATION-BASED VALIDATION

KW - DISEASE-FREE SURVIVAL

KW - POOR-PROGNOSIS

KW - CLINICAL-SIGNIFICANCE

KW - SERUM DNA

KW - POTENTIAL BIOMARKER

KW - RASSF1A METHYLATION

KW - ENDOCRINE THERAPY

KW - MULTIPLE GENES

U2 - 10.1186/s13058-020-1250-9

DO - 10.1186/s13058-020-1250-9

M3 - (Systematic) Review article

C2 - 32005275

SN - 1465-5411

VL - 22

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

M1 - 13

ER -