The relevance of genetic testing in young patients with breast fibroadenomas

Introduction. Fibroadenomas are the most common benign tumors of the mammary glands in children and adolescents. In some cases, they may be part of hereditary tumor predisposition syndromes associated with a high risk of developing malignant neoplasms throughout life, and therefore genetic testing is relevant.

The purpose of the study is to discribe the spectrum of genetic mutations in cancer-associated genes according to the results of next generation sequencing (NGS) in young patients with breast fibroadenomas.

Matherials and methods. Sixteen teenage girls with fibroadenomas of the breast who were followed up in Research Institute of Pediatric Oncology and Hematology from 2020 to 2023 were enrolled in this study. Genetic testing by NGS was performed.

Results. Pathogenic variants in cancer-associated genes were found in 4 (25 %) patients. In two cases, fibroadenomas were a part of Cowden’s syndrome associated with PTEN inactivation; two patients carried pathogenic variants in the BRCA1 and BRCA2 genes.

Conclusion. Genetic testing of young patients with breast fibroadenomas is important to optimize the management strategy in order to reduce cancer risk in high-risk groups of patients.

1. Gurkin Yu.A. Gynecology of adolescents. St. Petersburg: Foliant Publishing House LLC, 2000. 574 p. (In Russ.)].

2. Visotskaya I.V., Letyagin V.P., Vorotnikov I.K., Kim E.A., Kirsanov V.Yu., Polikarpova S.B. Focal Pathology of Mammary Glands in Teenage Girls. Voprosy sovremennoy pediatrii = Current Pediatrics. 2020;19(4):304–8. (In Russ.)].

3. Kidambi T.D., Kohli D.R., Samadder N.J., Singh A. Hereditary Polyposis Syndromes. Curr Treat Options Gastroenterol. 2019;17(4):650–65. doi: 10.1007/s11938-019-00251-4.

4. Bouys L., Bertherat J. Management of endocrine disease: Carney complex: clinical and genetic update 20 years after the identifi cation of the CNC1 (PRKAR1A) gene. Eur J Endocrinol. 2021;184(3):R99– R109. doi: 10.1530/EJE-20-1120.

5. Vohra L.M., Ali D., Hashmi S.A., Angez M. Breast cancer in a teenage girl with BRCA mutation: A case report from a low middle-income country. Int J Surg Case Rep. 2022;98:107513. doi: 10.1016/j.ijscr.2022.107513.

6. Mayer S., Gosemann J.H., Ure B.M., Metzelder M.L. Breast Disorders in Children and Adolescents. In: Pediatric Surgery. Puri P., Höllwarth M.E. (eds.). Springer, Cham, 2003. doi: 10.1007/978-3-030-81488-5_32.

7. Lozada J.R., Burke K.A., Maguire A. Myxoid fi broadenomas diff er from conventional fi broadenomas: a hypothesis-generating study. Histopathology. 2017;71(4):626–34. doi: 10.1111/his.13258.

8. Im C.J., Miller A., Balassanian R., Mukhtar R.A. Early onset, multiple, bilateral fi broadenomas of the breast: a case report. BMC Womens Health. 2021;21(1):170. doi: 10.1186/s12905-021-01311-7.

9. Amary M.F., Damato S., Halai D. Ollier disease and Maff ucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet. 2011;43(12):1262–5. doi: 10.1038/ng.994.

10. Fernández-Aguilar S., Buxant F., Noël J.C. Benign phyllodes tumor associated with Maff ucci’s syndrome. Breast. 2004;13(3):247–9. doi: 10.1016/j.breast.2003.06.001.

11. Cubitt J., Tungotyo M., Galiwango G. Maff ucci’s syndrome and fi broadenoma of the breast: a case report. Eur J Plast Surg. 2012;35:475–7. doi: 10.1007/s00238-011-0588-8.

12. Pansuriya T.C., Kroon H.M., Bovée J.V. Enchondromatosis: insights on the diff erent subtypes. Int J Clin Exp Pathol. 2010;3(6):557–69. PMID: 20661403.

13. Burdick D., Prior J.T. Peutz–Jeghers syndrome. A clinicopathologic study of a large family with a 27-year follow-up. Cancer. 1982;50(10):2139–46. doi: 10.1002/1097-0142(19821115)50:10<2139::aid-cncr2820501028>3.0.co;2-k.

14. Poh M.M., Ballard T.N., Wendel J.J. Beckwith–Wiedemann syndrome and juvenile fi broadenoma: a case report. Ann Plast Surg. 2010;64(6):803–6. doi: 10.1097/sap.0b013e3181b025f6.

15. Raine P.A., Noblett H.R., Houghton-Allen B.W., Campbell P.E. Breast fi broadenoma and cardiac anomaly associated with EMG (Beckwith– Wiedemann) syndrome. J Pediatr. 1979;94(4):633–4. doi: 10.1016/s0022-3476(79)80039-6.

16. Sokolova A., Johnstone K.J., McCart Reed A.E., Simpson P.T., Lakhani S.R. Hereditary breast cancer: syndromes, tumour pathology and molecular testing. Histopathology. 2023;82(1):70–82. doi: 10.1111/his.14808.

17. Cavazos T.B., Kachuri L., Graff R.E. Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies. BMC Med. 2022;20(1):332. doi: 10.1186/s12916-022-02535-6.