BRCAsearch: written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer

Martin P Nilsson, Therese Törngren, Karin Henriksson, Ulf Kristoffersson, Anders Kvist, Barbro Silfverberg, Åke Borg, Niklas Loman, Martin P Nilsson, Therese Törngren, Karin Henriksson, Ulf Kristoffersson, Anders Kvist, Barbro Silfverberg, Åke Borg, Niklas Loman

Abstract

Purpose: To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing.

Methods: In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling.

Results: During the period Feb 2, 2015-Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing.

Conclusions: Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.

Keywords: Breast cancer; Counseling; Genetic testing; Unselected.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Regional Ethical Review Board in Lund (Dnr 2009/659, Dnr 2014/681) and complies with the current laws of Sweden. The study has been performed in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Flowchart of patient inclusion for BRCAsearch and genetic analyses

References

    1. Kurian AW, Sigal BM, Plevritis SK. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol. 2010;28(2):222–231. doi: 10.1200/JCO.2009.22.7991.
    1. Heemskerk-Gerritsen BA, Rookus MA, Aalfs CM, Ausems MG, Collee JM, Jansen L, Kets CM, Keymeulen KB, Koppert LB, Meijers-Heijboer HE, Mooij TM, Tollenaar RA, Vasen HF, Hooning MJ, Seynaeve C. Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. Int J Cancer. 2015;136(3):668–677.
    1. Huzarski T, Byrski T, Gronwald J, Cybulski C, Oszurek O, Szwiec M, Gugala K, Stawicka M, Morawiec Z, Mierzwa T, Falco M, Janiszewska H, Kilar E, Marczyk E, Kozak-Klonowska B, Siolek M, Surdyka D, Wisniowski R, Posmyk M, Domagala P, Sun P, Lubinski J, Narod SA. The impact of oophorectomy on survival after breast cancer in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2016;156(2):371–378. doi: 10.1007/s10549-016-3749-4.
    1. Narod SA, Metcalfe K, Lynch HT, Ghadirian P, Robidoux A, Tung N, Gaughan E, Kim-Sing C, Olopade OI, Foulkes WD, Robson M, Offit K, Jakubowska A, Byrski T, Huzarski T, Sun P, Lubinski J. Should all BRCA1 mutation carriers with stage I breast cancer receive chemotherapy? Breast Cancer Res Treat. 2013;138(1):273–279. doi: 10.1007/s10549-013-2429-x.
    1. Nilsson MP, Hartman L, Kristoffersson U, Johannsson OT, Borg A, Henriksson K, Lanke E, Olsson H, Loman N. High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer. Breast Cancer Res Treat. 2014;147(3):571–578. doi: 10.1007/s10549-014-3115-3.
    1. Moller P, Hagen AI, Apold J, Maehle L, Clark N, Fiane B, Lovslett K, Hovig E, Vabo A. Genetic epidemiology of BRCA mutations–family history detects less than 50% of the mutation carriers. Eur J Cancer. 2007;43(11):1713–1717. doi: 10.1016/j.ejca.2007.04.023.
    1. Nilsson MP, Winter C, Kristoffersson U, Rehn M, Larsson C, Saal LH, Loman N. Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer. Fam Cancer. 2017
    1. Armstrong J, Toscano M, Kotchko N, Friedman S, Schwartz MD, Virgo KS, Lynch K, Andrews JE, Aguado Loi CX, Bauer JE, Casares C, Bourquardez Clark E, Kondoff MR, Molina AD, Abdollahian M, Walker G, Sutphen R. Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: the ABOUT Study. JAMA oncology. 2015;1(9):1251–1260. doi: 10.1001/jamaoncol.2015.3048.
    1. Kinney AY, Steffen LE, Brumbach BH, Kohlmann W, Du R, Lee JH, Gammon A, Butler K, Buys SS, Stroup AM, Campo RA, Flores KG, Mandelblatt JS, Schwartz MD. Randomized noninferiority trial of telephone delivery of BRCA1/2 genetic counseling compared with in-person counseling: 1-year follow-up. J Clin Oncol. 2016;34(24):2914–2924. doi: 10.1200/JCO.2015.65.9557.
    1. Schwartz MD, Valdimarsdottir HB, Peshkin BN, Mandelblatt J, Nusbaum R, Huang AT, Chang Y, Graves K, Isaacs C, Wood M, McKinnon W, Garber J, McCormick S, Kinney AY, Luta G, Kelleher S, Leventhal KG, Vegella P, Tong A, King L. Randomized noninferiority trial of telephone versus in-person genetic counseling for hereditary breast and ovarian cancer. J Clin Oncol. 2014;32(7):618–626. doi: 10.1200/JCO.2013.51.3226.
    1. Hoberg-Vetti H, Bjorvatn C, Fiane BE, Aas T, Woie K, Espelid H, Rusken T, Eikesdal HP, Listol W, Haavind MT, Knappskog PM, Haukanes BI, Steen VM, Hoogerbrugge N. BRCA1/2 testing in newly diagnosed breast and ovarian cancer patients without prior genetic counselling: the DNA-BONus study. Eur J Hum Genet. 2016;24(6):881–888. doi: 10.1038/ejhg.2015.196.
    1. Saal LH, Vallon-Christersson J, Hakkinen J, Hegardt C, Grabau D, Winter C, Brueffer C, Tang MH, Reutersward C, Schulz R, Karlsson A, Ehinger A, Malina J, Manjer J, Malmberg M, Larsson C, Ryden L, Loman N, Borg A. The Sweden Cancerome Analysis Network—Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine. Genome med. 2015;7(1):20. doi: 10.1186/s13073-015-0131-9.
    1. NCCN guidelines version 2.2017. Available at:
    1. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, Senn HJ. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Annals Oncol. 2013;24(9):2206–2223. doi: 10.1093/annonc/mdt303.
    1. Syrjakoski K, Vahteristo P, Eerola H, Tamminen A, Kivinummi K, Sarantaus L, Holli K, Blomqvist C, Kallioniemi OP, Kainu T, Nevanlinna H. Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients. J Natl Cancer Inst. 2000;92(18):1529–1531. doi: 10.1093/jnci/92.18.1529.
    1. van den Broek AJ, de Ruiter K, vant Veer LJ, Tollenaar RA, van Leeuwen FE, Verhoef S, Schmidt MK. Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population. Eur J Hum Genet. 2015;23(5):588–595. doi: 10.1038/ejhg.2014.161.
    1. George A, Riddell D, Seal S, Talukdar S, Mahamdallie S, Ruark E, Cloke V, Slade I, Kemp Z, Gore M, Strydom A, Banerjee S, Hanson H, Rahman N. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Scientific Rep. 2016;6:29506. doi: 10.1038/srep29506.
    1. Quinn VF, Meiser B, Kirk J, Tucker KM, Watts KJ, Rahman B, Peate M, Saunders C, Geelhoed E, Gleeson M, Barlow-Stewart K, Field M, Harris M, Antill YC, Cicciarelli L, Crowe K, Bowen MT, Mitchell G. Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial. Genet Med. 2016
    1. Sie AS, van Zelst-Stams WA, Spruijt L, Mensenkamp AR, Ligtenberg MJ, Brunner HG, Prins JB, Hoogerbrugge N. More breast cancer patients prefer BRCA-mutation testing without prior face-to-face genetic counseling. Fam Cancer. 2014;13(2):143–151.
    1. Voorwinden JS, Jaspers JP, ter Beest JG, Kievit Y, Sijmons RH, Oosterwijk JC. The introduction of a choice to learn pre-symptomatic DNA test results for BRCA or lynch syndrome either face-to-face or by letter. Clin Genet. 2012;81(5):421–429. doi: 10.1111/j.1399-0004.2011.01811.x.

Source: PubMed

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