Generate QR code
Open Access
Subscription Access
Clinical case of breast cancer associated with a pathogenic variant in the CHEK2 gene
https://doi.org/10.25557/2073-7998.2026.04.27-37
Abstract
We report a clinical case of pregnancy-associated breast cancer (PABC) in a woman carrying the pathogenic CHEK2 c.1100delC variant. The tumor was diagnosed postpartum and initially misinterpreted as lactostasis, which led to a delay in diagnosis at an advanced tumor size. The patient received a combined treatment regimen with a complete metabolic and pathological response, followed by confirmation of a hereditary cancer predisposition. This case highlights the biological features of PABC and the clinical implications of CHEK2 pathogenic variants, including elevated risk of contralateral breast cancer. The need for a personalized approach in diagnosis and treatment of young women with PABC is emphasized. The findings support the inclusion of the CHEK2 c.1100delC variant in standard PCR screening panels and underscore the lack of standardized guidelines for managing hereditary PABC cases.
Keywords
About the Authors
E. V. Kudryavtseva
Ural State Medical university; Ural Research Institute of Maternal and Child Health
Russian Federation
Russian Federation
3 Repina st., Yekaterinburg, 620028
1 Repina st., Yekaterinburg, 620028
E. R. Bikbulatova
Ural State Medical university
Russian Federation
Russian Federation
3 Repina st., Yekaterinburg, 620028
O. E. Knysh
Ural State Medical university
Russian Federation
Russian Federation
3 Repina st., Yekaterinburg, 620028
References
1. Paris I., Di Giorgio D., Carbognin L., et al. Pregnancy-Associated Breast Cancer: A Multidisciplinary Approach. Clin Breast Cancer. 2021;21(1):e120–7.
2. Vinatier E., Merlot B., Poncelet E., et al. Breast cancer during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2009;147(1):9–14.
3. Mavaddat N., Dorling L., Carvalho S., et al. Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes. JAMA Oncol. 2022;8(3):e216744.
4. Daly M.B., Rosenthal E., Cummings S., et al. The association between age at breast cancer diagnosis and prevalence of pathogenic variants. Breast Cancer Res Treat. 2023;199(3):617–26.
5. Momozawa Y., Iwasaki Y., Parsons M.T., et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018;9(1):4083.
6. Rummel S.K., Lovejoy .Lю, Shriver C.D., Ellsworth R.E. Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer. Breast Cancer Res Treat. 2017;164(3):593–601.
7. Zografos E., Korakiti A.M., Andrikopoulou A., et al. Germline mutations in a clinic-based series of pregnancy associated breast cancer patients. BMC Cancer. 2021;21(1):572.
8. Daly M.B., Pal T., Maxwell K.N., et al. NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024. J Natl Compr Canc Netw. 2023;21(10):1000–10.
9. Paluch-Shimon S., Cardoso F., Partridge A.H., et al. ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5). Ann Oncol Off J Eur Soc Med Oncol. 2022;33(11):1097–118.
10. Golotyuk M.A., Berezhnoj A.A., Kazanceva N.V., et al. Germinal’nyye mutatsii v genakh PALB2 i CHEK2 i nasledstvennyy rak [Germline mutations in the PALB2 and CHEK2 genes and hereditary cancer]. Ural’skiy meditsinskiy zhurnal [Ural Medical Journal]. 2023;22(3):126-136. (In Russ.)
11. Apostolou P., Papasotiriou I. Current perspectives on CHEK2 mutations in breast cancer. Breast Cancer Targets Ther. 2017;331–5.
12. ClinVar – NCBI [Internet]. National Center for Biotechnology Information (NCBI); 2025.
13. Shumilova S., Danishevich A., Nikolaev S., et al. High-and ModerateRisk Variants Among Breast Cancer Patients and Healthy Donors Enrolled in Multigene Panel Testing in a Population of Central Russia. Int J Mol Sci. 2024;25(23):12640.
14. Meijers-Heijboer H., Van den Ouweland A., Klijn J., et al. Lowpenetrance susceptibility to breast cancer due to CHEK2* 1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31(1).
15. Vahteristo P., Bartkova J., Eerola H., et al. A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet. 2002;71(2):432–8.
16. Bell D.W., Varley J.M., Szydlo T.E., et al. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999;286(5449):2528–31.
17. Loibl S., Azim Jr H.A., Bachelot T., et al. ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC). Ann Oncol. 2023;34(10):849–66.
18. Imyanitov E.N. Nasledstvennyy rak molochnoy zhelezy [Hereditary breast cancer]. Prakticheskaya onkologiya [Practical oncology]. 2010;11(4):258–66. (In Russ.)
19. Cheremokhin D.A., Deryabina S.S., Bikbulatova E.R., et al. Mutatsii gena CHEK2 i ikh rol’ v kantserogeneze molochnoy zhelezy [CHEK2 gene mutations and their role in breast carcinogenesis] (in Russ). Zhenskoye zdorov’ye i reproduktsiya [Women’s Health and Reproduction]. 2025;1(66). (In Russ.) DOI: 10.31550/2712-8598-2025-1-5-ZhZiR. URL: https://journalgynecology.ru/statyi/mutacii-gena-chek2-i-ih-rol-vkancerogeneze-molochnoj-zhelezy/ (Date of access: 20.07.2025)
20. Hing J.X., Mok C.W., Tan P.T., et al. Clinical utility of tumour marker velocity of cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) in breast cancer surveillance. Breast. 2020;52:95–101.
21. CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004;74(6):1175–82.
22. Kudryavtseva EV, Knysh OE, Petkau VV, Bikbulatova ER, Usynin IG. Genetic features of breast cancer patients and women with a cancer-prone family history. Meditsinskiy sovet = Medical Council. 2025;(21):130-140. (In Russ.) 23. Zolotykh M.A., Bilyalov A.I., Nesterova A.I., et al. Breast cancer: genetic personal risk factors: A review. J Mod Oncol. 2023;25(2):190–8.
23. Smid M., Schmidt M.K., Prager-van der Smissen W.J.C., et al. Breast cancer genomes from CHEK2 c. 1100delC mutation carriers lack somatic TP53 mutations and display a unique structural variant size distribution profile. Breast Cancer Res. 2023;25(1):53.
24. Margioula-Siarkou G., Margioula-Siarkou C., Petousis S., et al. Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes. Biology (Basel). 2023;12(3).
25. Zakharova N.V., Tereshin О.S., Bulinsky D.N., et al. Rak molochnoy zhelezy, assotsiirovannyy s beremennost’yu [Breast cancer associated with pregnancy]. Ural’skiy meditsinskiy zhurnal [Ural Medical Journal]. 2021;20(2):75-79. (In Russ.)
26. Lyons T.R., Schedin P.J., Borges V.F. Pregnancy and breast cancer: when they collide. J Mammary Gland Biol Neoplasia. 2009;14(2):87–98.
27. Andrieu N., Goldgar D.E., Easton D.F., et al. Pregnancies, breastfeeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS). J Natl Cancer Inst. 2006;98(8):535–44.
28. Lovegrove C. Pregnancy and breast cancer risk in women with BRCA1 or BRCA2 mutations. Nat Clin Pract Oncol. 2006;3(1):9. . doi:10.1038/ncponc0368
29. Bottalico M., Boldrini C. Giant triple negative pregnancy-associated breast cancer (PABC) in a young woman: From diagnosis to therapy step by step: A case report. Radiol Case Reports. 2025;20(3):1686–90.
30. Ivanova O.A., Zhil’tsova E.K., Ivanov V.G., et al. Rak molochnoy zhelezy i beremennost’: osobennosti diagnostiki i lecheniya [Breast cancer and pregnancy: diagnosis and treatment]. Zlokachestvennyye opukholi [Malignant tumours]. 2014;(1):14-18. (In Russ.)
31. Sorin V., Bufman H., Bernstein-Molho R., et al. Breast cancer screening in BRCA1/2 pathogenic sequence variant carriers during pregnancy and lactation. Clin Imaging. 2024;111:110189.
32. Wang B., Yang Y., Jiang Z., et al. Clinicopathological characteristics, diagnosis, and prognosis of pregnancy-associated breast cancer. Thorac cancer. 2019;10(5):1060–8.
33. Aleksandrova L.M., Kalinina A.M., Ipatov P.V., et al. Vyyavleniye raka molochnoy zhelezy: sostoyaniye problemy, puti resheniya Onkologiya [Detection of breast cancer: State-of-the-art, ways of solution]. Zhurnal im PA Gertsena [P.A. Herzen Journal of Oncology]. 2016;5(2):34-39. (In Russ.)
34. Imyanitov E.N., Krivorotko P.V,. Enaldieva D.A. Rak molochnoy zhelezy: kriterii vklyucheniya v programmu panel’nogo geneticheskogo testirovaniya mutatsiy BRCA1/2: uchebnoye posobiye dlya vrachey i obuchayushchikhsya v sisteme vysshego i dopolnitel’nogo professional’nogo obrazovaniya [Breast cancer: criteria for inclusion in the BRCA1/2 mutation panel genetic testing program: a textbook for doctors and students in the system of higher and additional professional education]. SPb NMITS onkologii im N.N. Petrova [St. Petersburg National Research Medical Center of Oncology named after N. Petrov]. 2023. – 48 p. (In Russ.)
35. Woodward E.R., van Veen E.M., Forde C., Het al. Clinical utility of testing for PALB2 and CHEK2 c.1100delC in breast and ovarian cancer. Genet Med Off J Am Coll Med Genet. 2021;23(10):1969–76.
36. Herrera-Pariente C., Capó-García R., Díaz-Gay M., et al. Identification of New Genes Involved in Germline Predisposition to Early-Onset Gastric Cancer. Int J Mol Sci. 2021;22(3).
37. Yanus G.A., Suspitsin E.N., Imyanitov E.N. The Spectrum of DiseaseAssociated Alleles in Countries with a Predominantly Slavic Population. Int J Mol Sci. 2024;25(17).
38. Sim W.C., Lee C.Y., Richards R., et al. Validation of a next generation sequencing assay for BRCA1, BRCA2, CHEK2 and PALB2 genetic testing. Exp Mol Pathol. 2020;116:104483.
39. Makhnoon S., Bednar E.M., Krause K.J., et al. Clinical management among individuals with variant of uncertain significance in hereditary cancer: a systematic review and meta-analysis. Clin Genet. 2021;100(2):119–31.
40. Cragun D., Weidner A., Tezak A., et al. Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers. Breast Cancer Res Treat. 2020;182(2):421–8.
41. Garmendia D., Weidner A., Venton L., Pal T. Comparing Cancer Risk Management between Females with Truncating CHEK2 1100delC versus Missense CHEK2 I157T Variants. Genes (Basel). 2024;15(7).
42. Secondino A., Starnone F., Veneruso I., et al. Evaluation of a FourGene Panel for Hereditary Cancer Risk Assessment. Genes (Basel). 2022;13(4).
43. Suelmann B.B.M., Bakhuis C.F.J., van Dooijeweert C., Vet al. Prognosis of pregnancy-associated breast cancer: inferior outcome in patients diagnosed during second and third gestational trimesters and lactation. Breast Cancer Res Treat. 2022;192(1):175–89.
44. Zagouri F., Psaltopoulou T., Dimitrakakis C., et al. Challenges in managing breast cancer during pregnancy. J Thorac Dis. 2013;5 Suppl 1(Suppl 1):S62-7.
45. Basta P., Bak A., Roszkowski K. Cancer treatment in pregnant women. Contemp Oncol (Poznan, Poland). 2015;19(5):354–60.
46. Pushkarev A.V., Galeev M.G., Pushkarev V.A., Sultanbaev A.V. Geneticheskiye prediktory razvitiya zlokachestvennykh novoobrazovaniy (obzor literatury) [Genetic Predictors of Malignancy: a Literature Review]. Kreativnaya khirurgiya i onkologiya [Creative surgery and oncology]. 2021;11(2):157-165. (In Russ.)
47. Schreurs M.A.C., Adank M.A., Hollestelle A., et al. Cohort profile: a nationwide study in Dutch CHEK2 c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands – Hebon-CHEK2. BMJ Open. 2024;14(10):e086688.
48. Graffeo R., Rana H.Q., Conforti F., et al. Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D. The Breast. 2022;65:32–40.
49. Tyulandin S.A., Zhukova L.G., Koroleva I.A., et al. Prakticheskiye rekomendatsii po lekarstvennomu lecheniyu raka molochnoy zhelezy [Practical recommendations for the drug treatment of breast cancer]. Zlokachestvennyye opukholi [Malignant tumors]. 2021;11(3S2- 1):119–57. (In Russ.)
50. Morra A., Mavaddat N., Muranen T.A., et al. The impact of coding germline variants on contralateral breast cancer risk and survival. Am J Hum Genet. 2023;110(3):475–86.
51. Kriege M., Hollestelle A., Jager A., et al. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. Br J Cancer. 2014;111(5):1004–13.
52. Morra A., Schreurs M.A.C., Andrulis I.L., et al. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer Med. 2023;12(15):16142–62.
53. Wang J., Wu S.G. Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives. Breast cancer (Dove Med Press. 2023;15:721–30.
54. Hanson H., Astiazaran-Symonds E., Amendola L.M., et al. Management of individuals with germline pathogenic/likely pathogenic variants in CHEK2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med Off J Am Coll Med Genet. 2023;25(10):100870.
Review
For citations:
Kudryavtseva E.V., Bikbulatova E.R., Knysh O.E. Clinical case of breast cancer associated with a pathogenic variant in the CHEK2 gene. Medical Genetics. 2026;25(4):27-37. (In Russ.) https://doi.org/10.25557/2073-7998.2026.04.27-37
Views:
110
JATS XML
Email this article 