Tamizaje para cáncer de mama con resonancia magné-tica en mujeres portadoras de mutaciones BRCA y no-BRCA

Carlos  Acevedo; Florencia Neffa; Fernando Lavista; Soledad Milans; Elisa Nuñez; Guianeya Santander; Carolina Vergara; Florencia Carusso; Daniela Fernández; Adriana Della Valle; Patricia Esperon

doi:10.29193/RMU.38.4.6

Authors

Carlos Acevedo Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas, Servicio de Mastología. Grupo Colaborativo Uruguayo
Florencia Neffa Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas. Grupo Colaborativo Uruguayo
Fernando Lavista Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas, Servicio de Imagenología. Grupo Colaborativo Uruguayo
Soledad Milans Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Departamento Clínico de Imagenología
Elisa Nuñez Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas, Servicio de Mastología. Grupo Colaborativo Uruguayo
Guianeya Santander Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas, Servicio de Oncología. Grupo Colaborativo Uruguayo
Carolina Vergara Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas. Grupo Colaborativo Uruguayo
Florencia Carusso Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas. Grupo Colaborativo Uruguayo
Daniela Fernández Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas. Grupo Colaborativo Uruguayo
Adriana Della Valle Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas, Servicio de Oncología. Grupo Colaborativo Uruguayo
Patricia Esperon Uruguay, Dirección Nacional de Sanidad de las Fuerzas Armadas. Grupo Colaborativo Uruguayo. Universidad de la República, Facultad de Química, Unidad de Genética Molecular

DOI:

https://doi.org/10.29193/RMU.38.4.6

Keywords:

BREAST NEOPLASMS, MAGNETIC RESONANCE, BRCA1 GENES, BRCA2 GENES, MUTATION, WOMEN

Abstract

Introduction: genetic propensity caused by germline pathogenic mutations explain up to 10% of breast cancer cases. Different strategies have been proposed to reduce its impact on women who are carriers of mutations, such as risk-reducing surgeries or breast magnetic resonance screening.
Method: observational, retrospective study analyzing the medical records of women who are carriers of germline pathogenic mutations to assess the different measures taken after the genetic test. Non-mastectomized patients were advised to join an annual MRI screening program and the percentage of adherence to plan was evaluated, along with biopsies performed and the number of breast cancer cases detected.
Results: 134 women carriers of germline pathogenic mutations were included in the study, with equal distributions in thirds for BRCA1, BRCA2 and non-BRCA genes. 64% of carriers of mutations who were subject to follow-up checkups joined the RMI screening program. The reasons why women failed to join the follow-up program were: the treating physician objected to the program (53%), the patients opposed to program (38%) and lack of resources (9%). Six biopsies were performed as a consequence of findings in the RMI, and one case of breast cancer was detected. Cancer incidence was 11 out of 1000 women - risk years.
Conclusions: our RMI follow-up program for women who are carriers of mutations managed to attract a high percentage of candidates. A significant amount of women failed to join the program because of their treating physician’s or their own disapproval. Evidence obtained reveals the dramatic need to reinforce educational programs that emphasize on the importance of RMI follow-up of high risk patients in our country.

References

1) Society of Gynecologic Oncology. Committee on Practice Bulletins–Gynecology, Committee on Genetics. Practice Bulletin No 182: He-reditary Breast and Ovarian Cancer Syndrome. Obstet Gynecol 2017; 130(3):e110-e126. doi: 10.1097/AOG.0000000000002296.
2) Whittemore A. Risk of breast cancer in carriers of BRCA gene mu-tations. N Engl J Med 1997; 337(11):788-9.
3) Wang Y, Jian J, Hung C, Peng H, Yang C, Cheng H, et al. Germline breast cancer susceptibility gene mutations and breast cancer out-comes. BMC Cancer 2018; 18(1):315. doi: 10.1186/s12885-018-4229-5.
4) Wendt C, Margolin S. Identifying breast cancer susceptibility genes - a review of the genetic background in familial breast cancer. Acta Oncol 2019; 58(2):135-46. doi: 10.1080/0284186X.2018.1529428.
5) Daly M, Pal T, Berry M, Buys S, Dickson P, Domchek S, et al. Ge-netic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19(1):77-102. doi: 10.6004/jnccn.2021.0001.
6) van Driel C, Eltahir Y, de Vries J, Jaspers J, Oosterwijk J, Mourits M, et al. Risk-reducing mastectomy in BRCA1/2 mutation carriers: factors influencing uptake and timing. Maturitas 2014; 77(2):180-4. doi: 10.1016/j.maturitas.2013.10.017.
7) Kurian A, Ward K, Hamilton A, Deapen D, Abrahamse P, Bondarenko I, et al. Uptake, results, and outcomes of germline multiple-gene sequencing after diagnosis of breast cancer. JAMA Oncol 2018; 4(8):1066-72. doi: 10.1001/jamaoncol.2018.0644.
8) Julian-Reynier C, Mancini J, Mouret-Fourme E, Gauthier-Villars M, Bonadona V, Berthet P, et al. Cancer risk management strategies and perceptions of unaffected women 5 years after predictive ge-netic testing for BRCA1/2 mutations. Eur J Hum Genet 2011; 19(5):500-6. doi: 10.1038/ejhg.2010.241.
9) Gail M, Brinton L, Byar D, Corle D, Green S, Schairer C, et al. Pro-jecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81(24):1879-86. doi: 10.1093/jnci/81.24.1879.
10) Tyrer J, Duffy S, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 2004; 23(7):1111-30. doi: 10.1002/sim.1668.
11) Saslow D, Boetes C, Burke W, Harms S, Leach M, Lehman C, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57(2):75-89. doi: 10.3322/canjclin.57.2.75.
12) Warner E, Plewes D, Hill K, Causer P, Zubovits J, Jong R, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004; 292(11):1317-25. doi: 10.1001/jama.292.11.1317.
13) Kuhl C, Weigel S, Schrading S, Arand B, Bieling H, König R, et al. Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J Clin Oncol 2010; 28(9):1450-7. doi: 10.1200/JCO.2009.23.0839.
14) Riedl C, Luft N, Bernhart C, Weber M, Bernathova M, Tea M, et al. Triple-modality screening trial for familial breast cancer under-lines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density. J Clin Oncol 2015; 33(10):1128-35. doi: 10.1200/JCO.2014.56.8626.
15) van Zelst J, Mus R, Woldringh G, Rutten M, Bult P, Vreemann S, et al. Surveillance of women with the BRCA1 or BRCA2 mutation by using biannual automated breast us, mr imaging, and mam-mography. Radiology 2017; 285(2):376-88. doi: 10.1148/radiol.2017161218.
16) Komenaka I, Ditkoff B, Joseph K, Russo D, Gorroochurn P, Ward M, et al. The development of interval breast malignancies in patients with BRCA mutations. Cancer 2004; 100(10):2079-83. doi: 10.1002/cncr.20221.
17) Kuhl C, Schrading S, Leutner C, Morakkabati-Spitz N, Wardelmann E, Fimmers R, et al. Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 2005; 23(33):8469-76. doi: 10.1200/JCO.2004.00.4960.
18) Riedl C, Ponhold L, Flöry D, Weber M, Kroiss R, Wagner T, et al. Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions dur-ing surveillance of women at high risk for breast cancer. Clin Cancer Res 2007; 13(20):6144-52. doi: 10.1158/1078-0432.CCR-07-1270.
19) Berg W. How well does supplemental screening magnetic resonance imaging work in high-risk women? J Clin Oncol 2014; 32(21):2193-6. doi: 10.1200/JCO.2014.56.2975.
20) Leach M, Boggis C, Dixon A, Easton D, Eeles R, Evans D, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005; 365(9473):1769-78. doi: 10.1016/S0140-6736(05)66481-1.
21) Wainberg S, Husted J. Utilization of screening and preventive surgery among unaffected carriers of a BRCA1 or BRCA2 gene mu-tation. Cancer Epidemiol Biomarkers Prev 2004; 13(12):1989-95.
22) Sohn V, Mosier A, Do W, Weiss J, McGregor H, Herbert G. Poor compliance in screening breast mri in high risk women in an equal access system. J Am Coll Surg 2017; 225(4 Suppl 2):e6. doi: 10.1016/j.jamcollsurg.2017.07.537.
23) Do W, Weiss J, McGregor H, Forte D, Sheldon R, Sohn V. Poor compliance despite equal access: Military experience with screening breast MRI in high risk women. Am J Surg 2019; 217(5):843-7. doi: 10.1016/j.amjsurg.2019.02.021.
24) Rijnsburger A, Obdeijn I, Kaas R, Tilanus-Linthorst M, Boetes C, Loo C, et al. BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study. J Clin Oncol 2010; 28(36):5265-73. doi: 10.1200/JCO.2009.27.2294.
25) Saadatmand S, Tilanus-Linthorst M, Rutgers E, Hoogerbrugge N, Oosterwijk J, Tollenaar R, et al. Cost-effectiveness of screening women with familial risk for breast cancer with magnetic resonance imaging. J Natl Cancer Inst 2013; 105(17):1314-21. doi: 10.1093/jnci/djt203.