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Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction.
Tüchler, Anja; De Pauw, Antoine; Ernst, Corinna; Anota, Amélie; Lakeman, Inge M M; Dick, Julia; van der Stoep, Nienke; van Asperen, Christi J; Maringa, Monika; Herold, Natalie; Blümcke, Britta; Remy, Robert; Westerhoff, Anke; Stommel-Jenner, Denise J; Frouin, Eléonore; Richters, Lisa; Golmard, Lisa; Kütting, Nadine; Colas, Chrystelle; Wappenschmidt, Barbara; Rhiem, Kerstin; Devilee, Peter; Stoppa-Lyonnet, Dominique; Schmutzler, Rita K; Hahnen, Eric.
Affiliation
  • Tüchler A; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • De Pauw A; Institut Curie, Department of Genetics, Paris, France; Université PSL, Paris, France.
  • Ernst C; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Anota A; Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon, France; Human and Social Sciences Department, Centre Léon Bérard, Lyon, France; French National Platform Quality of Life and Cancer, Centre Léon Bérard, Lyon, France.
  • Lakeman IMM; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • Dick J; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • van der Stoep N; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • van Asperen CJ; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • Maringa M; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Herold N; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Blümcke B; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Remy R; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Westerhoff A; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Stommel-Jenner DJ; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Frouin E; Université PSL, Paris, France; Clinical Bioinformatics Unit, Institut Curie, Paris, France.
  • Richters L; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Golmard L; Institut Curie, Department of Genetics, Paris, France; Université PSL, Paris, France.
  • Kütting N; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Colas C; Institut Curie, Department of Genetics, Paris, France; Université PSL, Paris, France; Institut Curie, Inserm U830, Paris, France.
  • Wappenschmidt B; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Rhiem K; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Devilee P; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • Stoppa-Lyonnet D; Institut Curie, Department of Genetics, Paris, France; Institut Curie, Inserm U830, Paris, France; Université Paris Cité, Paris, France.
  • Schmutzler RK; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany.
  • Hahnen E; Center for Familial Breast and Ovarian and Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital of Cologne, Cologne, Germany. Electronic address: eric.hahnen@uk-koeln.de.
Breast ; 73: 103615, 2024 Feb.
Article in En | MEDLINE | ID: mdl-38061307
ABSTRACT

BACKGROUND:

Breast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines.

METHODS:

For 425 cancer-free women with cancer FH (mean age 40·6 years, range 21-74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS306) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk. The proportions of women changing country-specific European risk categories for IBS recommendations, i.e. ≥20 % and ≥30 % eLTR, or ≥5 % e10YR were determined.

FINDINGS:

Of the women with non-informative PV status, including PRS306 and NGRFs changed clinical recommendations for 31·0 %, (57/184, 20 % eLTR), 15·8 % (29/184, 30 % eLTR) and 22·4 % (41/183, 5 % e10YR), respectively whereas of the women tested negative for a PV observed in their family, clinical recommendations changed for 16·7 % (25/150), 1·3 % (2/150) and 9·5 % (14/147). No change was observed for 82 women with PVs in high-risk genes (BRCA1/2, PALB2). Combined consideration of eLTRs and e10YRs identified BRCA1/2 PV carriers benefitting from IBS <30 years, and women tested non-informative/negative for whom IBS may be postponed.

INTERPRETATION:

For women who tested non-informative/negative, PRS and NGRFs have a considerable impact on IBS recommendations. Combined consideration of eLTRs and e10YRs allows personalizing IBS starting age.

FUNDING:

Horizon 2020, German Cancer Aid, Federal Ministry of Education and Research, Köln Fortune.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms Limits: Adult / Aged / Female / Humans / Middle aged Language: En Journal: Breast Journal subject: ENDOCRINOLOGIA / NEOPLASIAS Year: 2024 Document type: Article Affiliation country: Germany
Fulltext
Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms Limits: Adult / Aged / Female / Humans / Middle aged Language: En Journal: Breast Journal subject: ENDOCRINOLOGIA / NEOPLASIAS Year: 2024 Document type: Article Affiliation country: Germany