CASE REPORT article
Front. Oncol.
Sec. Breast Cancer
A combination of CHEK2 and high polygenic risk score leads to early-onset male breast cancer. Case Report
Kamil Tamindarov 1
Marika Frank 2,3
Sonja Wegscheider 2,3
Beatrix Benedix 4
Lingscheidt Thomas 5
Kai Neukirchner 5
Hadeel Shamma 6
Jens Schnabel 4
Marion Tolkmitt 4
Karina Pillau 4
Julia Hentschel 2
Diana Le Duc 7,8,2
1. University Hospital Carl Gustav Carus, Dresden, Germany
2. Universitat Leipzig Medizinische Fakultat, Leipzig, Germany
3. Center for Diagnostics, Human Genetics Department, Chemnitz Clinics, Chemnitz, Germany, Chemnitz, Germany
4. DRK Hospital Chemnitz Rabenstein, Women’s Hospital, Chemnitz, Germany
5. MVZ Diagnosticum GmbH, Stollberg-Niederdorf, Germany
6. Institute for Pathology, Chemnitz Clinics, Chemnitz, Germany
7. National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Dresden, Germany
8. Universitatsklinikum Carl Gustav Carus, Dresden, Germany
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Abstract
Male breast cancer (MBC) is a rare disease, accounting for about 1% of all breast cancer cases worldwide. Compared to female breast cancer (FBC), MBC shows a higher prevalence of hormone receptor positivity and distinct germline predispositions, most frequently pathogenic variants in BRCA2 and CHEK2. The contribution of mismatch repair (MMR) genes such as MSH6 to MBC risk remains, however, unclear. In addition, polygenic risk scores (PRS) have emerged as promising tools for breast cancer risk prediction but are not yet used in routine care. We report the case of a 42-year-old man diagnosed with invasive carcinoma of no special type, strongly estrogen receptor–positive, HER2-negative, and with a family history of breast and prostate cancer. Genetic testing revealed a pathogenic CHEK2 nonsense variant (p.Trp411*), a likely pathogenic MSH6 frameshift variant, and a breast cancer PRS in the 99th percentile. Tumor sequencing confirmed both germline variants but showed microsatellite stability and no loss of heterozygosity, arguing against a causal role of MSH6. This case illustrates how PRS, in combination with moderate-risk variants, like those in CHEK2, may drive early-onset MBC and highlights the need to incorporate polygenic models into risk assessment and counseling.
Summary
Keywords
case report, CHEK2, Male breast cancer, MSH6, Polygenic risk score
Received
10 December 2025
Accepted
18 February 2026
Copyright
© 2026 Tamindarov, Frank, Wegscheider, Benedix, Thomas, Neukirchner, Shamma, Schnabel, Tolkmitt, Pillau, Hentschel and Le Duc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Julia Hentschel; Diana Le Duc
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