Objective: To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university hospital. Methods: This was a retrospective analysis of the activity of our HFCU in its first 5 years of existence. Results: Between July 2010 and July 2015, 1,518 patients from 1,318 families attended our HFCU. Genetic testing was offered to 862 patients. Of those, 833 (96.6%) accepted testing, with available results for 636 (76.4%). Pathogenic mutations in BRCA1 and BRCA2 were found in 175 patients. Lynch syndrome and adenomatous polyposis were the most frequent syndromes diagnosed (151/175, 86.3%) among 17 different syndromes studied. Of the 404 patients without a previous genetic diagnosis in the family, 62 (15.3%) were found to have mutations in disease-causing genes. Prophylactic surgery and follow-up (33.7%) or follow-up only (66.3%) was proposed for mutation carriers according to international guidelines and patients' preferences. Conclusion: We have a high mutation detection rate, genetic test acceptance, and compliance with risk reduction strategies. However, there is room for improvement, especially in genetic testing timing, considering that an increase in the indications for genetic testing is expected.

1.
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee: A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med 2015;17:70-87.
2.
Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R, Pichert G, Van t'veer L, Tung N, Weitzel JN, Couch FJ, Rubinstein WS, Ganz PA, Daly MB, Olopade OI, Tomlinson G, Schildkraut J, Blum JL, Rebbeck TR: Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967-975.
3.
Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, De La Chapelle A, Mecklin JP: Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118:829-834.
4.
Gala M, Chung DC: Hereditary colon cancer syndromes. Semin Oncol 2011;38:490-499.
5.
Raue F, Frank-Raue K: Update multiple endocrine neoplasia type 2. Fam Cancer 2010;9:449-457.
6.
Byrski T, Huzarski T, Dent R, Gronwald J, Zuziak D, Cybulski C, Kladny J, Gorski B, Lubinski J, Narod SA: Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 2009;115:359-363.
7.
Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 2010;376:245-251.
8.
Zon RT, Goss E, Vogel VG, Chlebowski RT, Jatoi I, Robson ME, Wollins DS, Garber JE, Brown P, Kramer BS; American Society of Clinical Oncology: American Society of Clinical Oncology policy statement: the role of the oncologist in cancer prevention and risk assessment. J Clin Oncol 2009;27:986-993.
9.
Marquez-Rodas I, Lopez-Trabada D, Ruperez Blanco AB, Custodio Cabello S, Peligros Gomez MI, Orera Clemente M, Calvo FA, Martin M: Family history record and hereditary cancer risk perception according to National Cancer Institute criteria in a Spanish medical oncology service: a retrospective study. Oncology 2012;82:30-34.
10.
Marquez-Rodas I, Lopez-Tarruella S, Jerez Y, Cavanagh M, Custodio S, Lopez-Trabada D, Moya B, Perez S, Ruperez AB, Martin M: Evaluation of a heredofamilial cancer unit in increasing family history collection and genetic counseling referrals among Spanish oncologists at a university hospital. J Genet Couns 2014;23:108-113.
11.
Lindor NM, McMaster ML, Lindor CJ, Greene MH; National Cancer Institute, Division of Cancer Prevention, Community Oncology and Prevention Trials Research Group: Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr 2008;38:1-93.
12.
Kastrinos F, Steyerberg EW, Balmana J, Mercado R, Gallinger S, Haile R, Casey G, Hopper JL, LeMarchand L, Lindor NM, Newcomb PA, Thibodeau SN, Syngal S; Colon Cancer Family Registry: Comparison of the clinical prediction model PREMM(1,2,6) and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer. Gut 2013;62:272-279.
13.
Lee SC, Bernhardt BA, Helzlsouer KJ: Utilization of BRCA1/2 genetic testing in the clinical setting: report from a single institution. Cancer 2002;94:1876-1885.
14.
Peterson EA, Milliron KJ, Lewis KE, Goold SD, Merajver SD: Health insurance and discrimination concerns and BRCA1/2 testing in a clinic population. Cancer Epidemiol Biomarkers Prev 2002;11:79-87.
15.
Wang G, Beattie MS, Ponce NA, Phillips KA: Eligibility criteria in private and public coverage policies for BRCA genetic testing and genetic counseling. Genet Med 2011;13:1045-1050.
16.
Olaya W, Esquivel P, Wong JH, Morgan JW, Freeberg A, Roy-Chowdhury S, Lum SS: Disparities in BRCA testing: when insurance coverage is not a barrier. Am J Surg 2009;198:562-565.
17.
Bernhardt C, Schwan AM, Kraus P, Epplen JT, Kunstmann E: Decreasing uptake of predictive testing for Huntington's disease in a German centre: 12 years' experience (1993-2004). Eur J Hum Genet 2009;17:295-300.
18.
Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, Horick N, Yang S, Shannon KM, Tung N, Ford JM, Lincoln SE, Ellisen LW: Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol 2015;1:943-951.
19.
Frey MK, Kim SH, Bassett RY, Martineau J, Dalton E, Chern JY, Blank SV: Rescreening for genetic mutations using multi-gene panel testing in patients who previously underwent non-informative genetic screening. Gynecol Oncol 2015;139:211-215.
20.
Slavin TP, Niell-Swiller M, Solomon I, Nehoray B, Rybak C, Blazer KR, Weitzel JN: Corrigendum: Clinical application of multigene panels: challenges of next-generation counseling and cancer risk management. Front Oncol 2015;5:271.
21.
Kurian AW, Hare EE, Mills MA, Kingham KE, McPherson L, Whittemore AS, McGuire V, Ladabaum U, Kobayashi Y, Lincoln SE, Cargill M, Ford JM: Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. J Clin Oncol 2014;32:2001-2009.
22.
Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012;366:1382-1392.
23.
Llort G, Chirivella I, Morales R, Serrano R, Sanchez AB, Teule A, Lastra E, Brunet J, Balmana J, Grana B; SEOM Hereditary Cancer Working Group: SEOM clinical guidelines in hereditary breast and ovarian cancer. Clin Transl Oncol 2015;17:956-961.
24.
Eccles DM, Balmana J, Clune J, Ehlken B, Gohlke A, Hirst C, Potter D, Schroeder C, Tyczynski JE, Gomez Garcia EB: Selecting patients with ovarian cancer for germline BRCA mutation testing: findings from guidelines and a systematic literature review. Adv Ther 2016;33:129-150.
25.
Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 2010;376:235-244.
26.
Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS: DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med 2015;373:1697-1708.
27.
Staudigl C, Pfeiler G, Hrauda K, Renz R, Berger A, Lichtenschopf R, Singer CF, Tea MK: Changes of socio-demographic data of clients seeking genetic counseling for hereditary breast and ovarian cancer due to the “Angelina Jolie Effect.” BMC Cancer 2016;16:436.
28.
Márquez-Rodas I, Flores-Sanchez C, Sanz M, Luque S, Gonzalez Asanza C, Peligros I, Díe M, Mata C, Solera J, Martín M: 5 años después: experiencia y retos en el manejo multidisciplinar del cáncer hereditario en el Hospital General Universitario Gregorio Marañón. XV Congreso SEOM, Madrid, October 28-30, 2015.
29.
Moreno L, Linossi C, Esteban I, Gadea N, Carrasco E, Bonache S, Gutierrez-Enriquez S, Cruz C, Diez O, Balmana J: Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics. Clin Transl Oncol 2016;18:981-987.
30.
Vasen HF, Abdirahman M, Brohet R, Langers AM, Kleibeuker JH, van Kouwen M, Koornstra JJ, Boot H, Cats A, Dekker E, Sanduleanu S, Poley JW, Hardwick JC, de Vos Tot Nederveen Cappel WH, van der Meulen-de Jong AE, Tan TG, Jacobs MA, Mohamed FL, de Boer SY, van de Meeberg PC, Verhulst ML, Salemans JM, van Bentem N, Westerveld BD, Vecht J, Nagengast FM: One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology 2010;138:2300-2306.
31.
Auranen A, Joutsiniemi T: A systematic review of gynecological cancer surveillance in women belonging to hereditary nonpolyposis colorectal cancer (Lynch syndrome) families. Acta Obstet Gynecol Scand 2011;90:437-444.
32.
Metcalfe K, Gershman S, Ghadirian P, Lynch HT, Snyder C, Tung N, Kim-Sing C, Eisen A, Foulkes WD, Rosen B, Sun P, Narod SA: Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ 2014;348:g226.
33.
Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, Murphy J, Ghadirian P, Friedman E, Foulkes WD, Kim-Sing C, Wagner T, Tung N, Couch F, Stoppa-Lyonnet D, Ainsworth P, Daly M, Pasini B, Gershoni-Baruch R, Eng C, Olopade OI, McLennan J, Karlan B, Weitzel J, Sun P, Narod SA; Hereditary Ovarian Cancer Clinical Study Group: Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 2006;296:185-192.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.