Genetic and Clinical Implications of BRCA Mutations in Hereditary Breast and Ovarian Cancer Syndrome (HBOC): A Review
DOI:
https://doi.org/10.47611/jsrhs.v13i4.8274Keywords:
BRCA, HBOC, Hereditary Breast and Ovarian Cancer, Breast Cancer, Ovarian Cancer, Genetic, Clinical, Mutations, BRCA Mutations, HBOC Syndrome, Hereditary Breast and Ovarian Cancer SyndromeAbstract
BRCA1 and BRCA2 mutations are critical in Hereditary Breast and Ovarian Cancer (HBOC) syndrome, influencing cancer risk and treatment strategies. This review synthesizes findings from recent studies on these mutations, noting that BRCA1 mutations are linked with a higher risk of breast and ovarian cancers than BRCA2. For instance, BRCA1 mutations show a lifetime breast cancer risk of 55-72% and ovarian cancer risk of 39-44%, while BRCA2 mutations show a 45-69% risk for breast cancer and 11-17% for ovarian cancer. Variability in risk estimates is attributed to differences in study design, sample size, and methodology. Large, long-term studies generally provide more stable estimates. Effective management strategies include regular screenings and preventive surgeries. Future research should focus on standardizing methodologies and considering diverse factors to enhance risk management for BRCA mutation carriers.
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Alemar, B., Herzog, J., Brinckmann, C., Artigalás, O., Vanessa, I., Matzenbacher Bittar, C., Ashton-Prolla, P., and Weitzel, J.N. (2016). Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. Cancer Genetics, 209(9), pp.417–422. doi:https://doi.org/10.1016/j.cancergen.2016.06.008.
Anne-Marie, B., Manria, P., Hanhauser, Y., Mc Garrigle, S., Spillane, C.M., Byrne, N., Amanda, D., Prizeman, G., and Elizabeth, C. (2024). Information needs of women with BRCA mutations regarding cancer risk management and decision-making. European Journal of Oncology Nursing, pp.102627–102627. doi:https://doi.org/10.1016/j.ejon.2024.102627.
Calabrese, A., von Arx, C., Tafuti, A.A., Pensabene, M., and De Laurentiis, M. (2024). Prevention, diagnosis and clinical management of hereditary breast cancer beyond BRCA1/2 genes. Cancer Treatment Reviews, 129, pp.102785–102785. doi:https://doi.org/10.1016/j.ctrv.2024.102785.
Carnevali, I., Riva, C., Chiaravalli, A.M., Sahnane, N., Di Lauro, E., Viel, A., Rovera, F., Formenti, G., Ghezzi, F., Sessa, F., and Tibiletti, M.G. (2019). Inherited cancer syndromes in 220 Italian ovarian cancer patients. Cancer Genetics, 237, pp.55–62. doi:https://doi.org/10.1016/j.cancergen.2019.06.005.
Castéra, L., Harter, V., Muller, E., Krieger, S., Goardon, N., Ricou, A., Rousselin, A., Paimparay, G., Legros, A., Bruet, O., Quesnelle, C., Domin, F., San, C., Brault, B., Fouillet, R., Abadie, C., Béra, O., Berthet, P., Frébourg, T., and Vaur, D. (2018). Landscape of pathogenic variations in a panel of 34 genes and cancer risk estimation from 5131 HBOC families. Genetics in Medicine, 20(12), pp.1677–1686. doi:https://doi.org/10.1038/s41436-018-0005-9.
Castillo-Guardiola, V., Rosado-Jiménez, L., Sarabia-Meseguer, M.D., Marín-Vera, M., Macías-Cerrolaza, J.A., García-Hernández, R., Zafra-Poves, M., Sánchez-Henarejos, P., Moreno-Locubiche, M.Á., Cuevas-Tortosa, E., Arnaldos-Carrillo, M., Ayala de la Peña, F., Alonso-Romero, J.L., Noguera-Velasco, J.A., and Ruiz-Espejo, F. (2022). Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance. European Journal of Medical Genetics, 65(4), p.104468. doi:https://doi.org/10.1016/j.ejmg.2022.104468.
Dawoud, A., Zakaria, I., Rashwan, H., Braoudaki, M., and Youness, R.A. (2023). Circular RNAs: New layer of complexity evading breast cancer heterogeneity. Non-coding RNA Research, 8(1), pp.60–74. doi:https://doi.org/10.1016/j.ncrna.2022.09.011.
Fanale, D., Corsini, L.R., Pedone, E., Randazzo, U., Fiorino, A., Di Piazza, M., Brando, C., Magrin, L., Contino, S., Piraino, P., Bazan Russo, T.D., Cipolla, C., Russo, A., and Bazan, V. (2023). Potential agnostic role of BRCA alterations in patients with several solid tumors: One for all, all for one? Critical Reviews in Oncology/Hematology, [online] 190, p.104086. doi:https://doi.org/10.1016/j.critrevonc.2023.104086.
Fanale, D., Pivetti, A., Cancelliere, D., Spera, A., Bono, M., Fiorino, A., Pedone, E., Barraco, N., Brando, C., Perez, A., Guarneri, M.F., Russo, T.D.B., Vieni, S., Guarneri, G., Russo, A., and Bazan, V. (2022). BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: looking for the hidden meaning. Critical Reviews in Oncology/Hematology, p.103626. doi:https://doi.org/10.1016/j.critrevonc.2022.103626.
Fernández Madrigal, L., Rodríguez Garcés, M.Y., and Jiménez Ruiz, F.J. (2023). Impact of non-BRCA genes in the indication of risk-reducing surgery in hereditary breast and ovarian cancer syndrome (HBOC). Current Problems in Cancer, [online] p.101008. doi:https://doi.org/10.1016/j.currproblcancer.2023.101008.
Gomez Garcia, E.M., Hernandez-Martinez, N.L., Lechuga-Becerra, L., Trujillo-Gomez, D., and Valdez-Rade, J. (2022). 578P Genotype-phenotype correlation in diverse pathogenic variants in BRCA genes in patients with ovarian cancer: Focusing in prognosis and predictive role of each one. Annals of Oncology, 33, pp.S811–S811. doi:https://doi.org/10.1016/j.annonc.2022.07.706.
Jackson, L., Weedon, M.N., Green, H., Mallabar-Rimmer, B., Harrison, J.W., Wood, A.R., Ruth, K., Tyrrell, J., and Wright, C.F. (2023). Influence of family history on penetrance of hereditary cancers in a population setting. EClinicalMedicine, 64, pp.102159–102159. doi:https://doi.org/10.1016/j.eclinm.2023.102159.
Marmolejo, D.H., Wong, M.Y.Z., Bajalica-Lagercrantz, S., Tischkowitz, M., Balmaña, J., Patócs, A.B., Chappuis, P., Colas, C., Genuardi, M., Haanpää, M., Vetti, H.H., Hoogerbrugge, N., Irmejs, A., Kahre, T., Klink, B., Krajc, M., Milagre, T.H., de Putter, R., Steinke-Lange, V., and Wadt, K. (2021). Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe. European Journal of Medical Genetics, [online] 64(12), p.104350. doi:https://doi.org/10.1016/j.ejmg.2021.104350.
Morrow, M. (2021). Surgery and prophylactic surgery in hereditary breast cancer. The Breast. doi:https://doi.org/10.1016/j.breast.2021.12.010.
Nunziato, M., Scaglione, G.L., Maggio, F., Nardelli, C., Capoluongo, E., and Salvatore, F. (2023). The performance of multi-gene panels for breast/ovarian cancer predisposition. Clinica Chimica Acta, 539, pp.151–161. doi:https://doi.org/10.1016/j.cca.2022.12.007.
Powell, C.B., Laurent, C., Garcia, C., Hoodfar, E., Karlea, A., Kobelka, C., Lee, J., Roh, J., and Kushi, L.H. (2022). Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system. Gynecologic Oncology, 167(3), pp.467–475. doi:https://doi.org/10.1016/j.ygyno.2022.10.001.
Robinson, L.S., Hendrix, A., Xian Jin Xie, Yan, J., Pirzadeh-Miller, S., Pritzlaff, M., Read, P., Pass, S., Euhus, D., and Ross, T.S. (2015). Prediction of Cancer Prevention: From Mammogram Screening to Identification of BRCA1 / 2 Mutation Carriers in Underserved Populations. doi:https://doi.org/10.1016/j.ebiom.2015.10.022
Schwab LP, Peacock DL, Majumdar D, Ingels JF, Jensen LC, Smith KD, Cushing RC, Seagroves TN. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res. 2012 Jan 7;14(1): R6. doi: 10.1186/bcr3087. PMID: 22225988; PMCID: PMC3496121.
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