A Rare Case of Triple-Negative Breast Cancer with RAD51D Gene Mutation TNBC with RAD51D gene mutation
Abstract
Background: The heterogeneity of breast cancer (BC) subtypes poses a significant challenge, with carcinogenesis involving multiple stages and genes, including proto-oncogenes, tumor suppressor genes, and DNA repair genes. Next-generation sequencing has expanded access to multigene panels, such as RAD51 paralogs, which increase the risk of ovarian cancer and possibly triple-negative (TN) BC.
Case presentation: We present a rare case of a 45-year-old woman with TNBC and a RAD51D gene mutation. Mammography and breast ultrasonography revealed an irregular, 30 mm hypoechoic area and dystrophic calcifications in the right breast. Immunohistochemistry showed a lack of expression of ER, RP, HER-2, and P53, with 50% of neoplastic cell nuclei positive for Ki-67. Next-generation sequencing revealed a mutation in RAD51D and MUYTH genes. The patient underwent partial mastectomy, chemotherapy, and prophylactic mastectomy.
Conclusion: Genetic analysis is crucial for identifying specific mutations contributing to TNBC development. Current preventive interventions primarily address BRCA1 and BRCA2 mutations, following established guidelines.
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References
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. doi: 10.1002/ijc.29210.
Majeed W, Aslam B, Javed I, Khaliq T, Muhammad F, Ali A, et al. Breast cancer: major risk factors and recent developments in treatment. Asian Pac J Cancer Prev. 2014;15(8):3353–8. doi: 10.7314/apjcp.2014.15.8.3353.
Dine J, Deng CX. Mouse models of BRCA1 and their application to breast cancer research. Cancer Metastasis Rev. 2013;32(1-2):25–37. doi: 10.1007/s10555-012-9403-7.
Song H, Dicks E, Ramus SJ, Tyrer JP, Intermaggio MP, Hayward J, et al. Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. J Clin Oncol. 2015;33(26):2901–7. doi: 10.1200/JCO.2015.61.2408.
Cobain EF, Milliron KJ, Merajver SD. Updates on breast cancer genetics: Clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer. Semin Oncol. 2016;43(5):528–35. doi: 10.1053/j.seminoncol.2016.10.001.
Balmaña J, Díez O, Rubio IT, Cardoso F; ESMO Guidelines Working Group. BRCA in breast cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22 Suppl 6:vi31–4. doi: 10.1093/annonc/mdr373.
Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso MJ, Gilbert F, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016;27(suppl 5):v103–10. doi: 10.1093/annonc/mdw327.
Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481(7381):287–94. doi: 10.1038/nature10760.
Jiang Q, Greenberg RA. Deciphering the BRCA1 Tumor Suppressor Network. J Biol Chem. 2015;290(29):17724–32. doi: 10.1074/jbc.R115.667931.
Jancárková N, Zikán M, Pohlreich P, Freitag P, Matous B. Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary. Ceska Gynekol. 2003;68(1):11–6.
Dutil J, Colon-Colon JL, Matta JL, Sutphen R, Echenique M. Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico. Cancer Genet. 2012;205(5):242–8. doi: 10.1016/j.cancergen.2012.04.002.
Cao L, Niu Y. Triple negative breast cancer: special histological types and emerging therapeutic methods. Cancer Biol Med. 2020;17(2):293–306. doi: 10.20892/j.issn.2095-3941.2019.0465.
Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev. 2012;21(1):134–47. doi: 10.1158/1055-9965.EPI-11-0775.
Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938–48. doi: 10.1056/NEJMra1001389.
Robertson L, Hanson H, Seal S, Warren-Perry M, Hughes D, Howell I, et al. BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years. Br J Cancer. 2012;106(6):1234–8. doi: 10.1038/bjc.2012.31.
Aysola K, Desai A, Welch C, Xu J, Qin Y, Reddy V, et al. Triple Negative Breast Cancer - An Overview. Hereditary Genet. 2013;2013(Suppl 2):001. doi: 10.4172/2161-1041.S2-001.
Ellsworth DL, Turner CE, Ellsworth RE. A Review of the Hereditary Component of Triple Negative Breast Cancer: High- and Moderate-Penetrance Breast Cancer Genes, Low-Penetrance Loci, and the Role of Nontraditional Genetic Elements. J Oncol. 2019;2019:4382606. doi: 10.1155/2019/4382606.
Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet. 2011;43(9):879-82. doi: 10.1038/ng.893.
Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet. 2010;42(5):410-4. doi: 10.1038/ng.569.
Koczorowska AM, Białkowska A, Kluzek K, Zdzienicka MZ. The role of the Fanconi anemia pathway in DNA repair and maintenance of genome stability. Postepy Hig Med Dosw. 2014;68:459-72. doi: 10.5604/17322693.1101567.
Taniguchi, T. Abstract IA13: The Fanconi anemia-BRCA pathway and chemosensitivity of cancer cells. Clinical Cancer Research. 2013;19(19_Supplement):IA13.
Moldovan GL, D'Andrea AD. How the fanconi anemia pathway guards the genome. Annu Rev Genet. 2009;43:223-49. doi: 10.1146/annurev-genet-102108-134222.
Daly MB, Pilarski R, Yurgelun MB, Berry MP, Buys SS, Dickson P, et al. NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020. J Natl Compr Canc Netw. 2020;18(4):380–91. doi: 10.6004/jnccn.2020.0017.
Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science. 2017;355(6330):1152–8. doi: 10.1126/science.aam7344.
Spinelli C, Strambi S, Piccini L, Rossi L, Aretini P, Caligo A. BRCA1 gene variant p.P142H associated with male breast cancer: a two-generation genealogic study and literature review. Fam Cancer. 2015;14(4):515-9. doi: 10.1007/s10689-015-9819-7.
Giannakeas V, Lim DW, Narod SA. Bilateral Mastectomy and Breast Cancer Mortality. JAMA Oncol. 2024:e242212. doi: 10.1001/jamaoncol.2024.2212.
Murphy JO, Sacchini VS. Breast cancer in BRCA mutation carriers: breast-conserving therapy or bilateral mastectomy?. Clinical Practice. 2013;10(6):751-764
King L, O'Neill SC, Spellman E, Peshkin BN, Valdimarsdottir H, Willey S, et al. Intentions for bilateral mastectomy among newly diagnosed breast cancer patients. J Surg Oncol. 2013;107(7):772-6. doi: 10.1002/jso.23307.
Metcalfe KA. Prophylactic bilateral mastectomy for breast cancer prevention. J Womens Health (Larchmt). 2004;13(7):822-9. doi: 10.1089/jwh.2004.13.822.
Noditi A, Caragheorghe G, Stoleru S, Blidaru A, Bordea CI. Contralateral Prophylactic Mastectomy in Patients with Breast Cancer. Chirurgia (Bucur). 2021;116(2 Suppl):73-83.
Torres-Esquius S, Llop-Guevara A, Gutiérrez-Enríquez S, Romey M, Teulé À, Llort G, et al. Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer. JAMA Netw Open. 2024;7(4):e247811. doi: 10.1001/jamanetworkopen.2024.7811.
Hanson H, Kulkarni A, Loong L, Kavanaugh G, Torr B, Allen S, et al. UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes: RAD51C, RAD51D, BRIP1 and PALB2. J Med Genet. 2023;60(5):417-29. doi: 10.1136/jmg-2022-108898.
Suszynska M, Klonowska K, Jasinska AJ, Kozlowski P. Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes. Gynecol Oncol. 2019;153(2):452–62. doi: 10.1016/j.ygyno.2019.01.027.
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