Behavioral and psychosocial effects of rapid genetic counseling and testing in newly diagnosed breast cancer patients: design of a multicenter randomized clinical trial

Marijke R Wevers, Margreet G E M Ausems, Senno Verhoef, Eveline M A Bleiker, Daniela E E Hahn, Frans B L Hogervorst, Rob B van der Luijt, Heiddis B Valdimarsdottir, Richard van Hillegersberg, Emiel J T H Rutgers, Neil K Aaronson, Marijke R Wevers, Margreet G E M Ausems, Senno Verhoef, Eveline M A Bleiker, Daniela E E Hahn, Frans B L Hogervorst, Rob B van der Luijt, Heiddis B Valdimarsdottir, Richard van Hillegersberg, Emiel J T H Rutgers, Neil K Aaronson

Abstract

Background: It has been estimated that between 5% and 10% of women diagnosed with breast cancer have a hereditary form of the disease, primarily caused by a BRCA1 or BRCA2 gene mutation. Such women have an increased risk of developing a new primary breast and/or ovarian tumor, and may therefore opt for preventive surgery (e.g., bilateral mastectomy, oophorectomy). It is common practice to offer high-risk patients genetic counseling and DNA testing after their primary treatment, with genetic test results being available within 4-6 months. However, some non-commercial laboratories can currently generate test results within 3 to 6 weeks, and thus make it possible to provide rapid genetic counseling and testing (RGCT) prior to primary treatment. The aim of this study is to determine the effect of RGCT on treatment decisions and on psychosocial health.

Methods/design: In this randomized controlled trial, 255 newly diagnosed breast cancer patients with at least a 10% risk of carrying a BRCA gene mutation are being recruited from 12 hospitals in the Netherlands. Participants are randomized in a 2:1 ratio to either a RGCT intervention group (the offer of RGCT directly following diagnosis with tests results available before surgical treatment) or to a usual care control group. The primary behavioral outcome is the uptake of direct bilateral mastectomy or delayed prophylactic contralateral mastectomy. Psychosocial outcomes include cancer risk perception, cancer-related worry and distress, health-related quality of life, decisional satisfaction and the perceived need for and use of additional decisional counseling and psychosocial support. Data are collected via medical chart audits and self-report questionnaires administered prior to randomization, and at 6 month and at 12 month follow-up.

Discussion: This trial will provide essential information on the impact of RGCT on the choice of primary surgical treatment among women with breast cancer with an increased risk of hereditary cancer. This study will also provide data on the psychosocial consequences of RGCT and of risk-reducing behavior.

Trial registration: The study is registered at the Netherlands Trial Register (NTR1493) and ClinicalTrials.gov (NCT00783822).

Figures

Figure 1
Figure 1
Study flow diagram.

References

    1. Turnbull C, Hodgson S. Genetic predisposition to cancer. Clin Med. 2005;5:491–498.
    1. Vasen HF, Tesfay E, Boonstra H, Mourits MJ, Rutgers E, Verheyen R, Oosterwijk J, Beex L. Early detection of breast and ovarian cancer in families with BRCA mutations. Eur J Cancer. 2005;41:549–554. doi: 10.1016/j.ejca.2004.10.029.
    1. Evans DG, Lalloo F, Hopwood P, Maurice A, Baildam A, Brain A, Barr L, Howell A. Surgical decisions made by 158 women with hereditary breast cancer aged <50 years. Eur J Surg Oncol. 2005;31:1112–1118. doi: 10.1016/j.ejso.2005.05.007.
    1. van der Hout AH, van den Ouweland AM, van der Luijt RB, Gille HJ, Bodmer D, Bruggenwirth H, Mulder IM, van der Vlies P, Elfferich P, Huisman MT, ten Berge AM, Kromosoeto J, Jansen RP, van Zon PH, Vriesman T, Arts N, Lange MB, Oosterwijk JC, Meijers-Heijboer H, Ausems MG, Hoogerbrugge N, Verhoef S, Halley DJ, Vos YJ, Hogervorst F, Ligtenberg M, Hofstra RM. A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. Hum Mutat. 2006;27:654–666. doi: 10.1002/humu.20340.
    1. Eccles DM. Identification of personal risk of breast cancer: genetics. Breast Cancer Res. 2008;10(Suppl 4):S12. doi: 10.1186/bcr2172.
    1. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995;56:265–271.
    1. Narod SA, Offit K. Prevention and management of hereditary breast cancer. J Clin Oncol. 2005;23:1656–1663. doi: 10.1200/JCO.2005.10.035.
    1. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22:2328–2335. doi: 10.1200/JCO.2004.04.033.
    1. Graeser MK, Engel C, Rhiem K, Gadzicki D, Bick U, Kast K, Froster UG, Schlehe B, Bechtold A, Arnold N, Preisler-Adams S, Nestle-Kraemling C, Zaino M, Loeffler M, Kiechle M, Meindl A, Varga D, Schmutzler RK. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27:5887–5892. doi: 10.1200/JCO.2008.19.9430.
    1. Schwartz MD, Peshkin BN, Hughes C, Main D, Isaacs C, Lerman C. Impact of BRCA1/BRCA2 mutation testing on psychologic distress in a clinic-based sample. J Clin Oncol. 2002;20:514–520. doi: 10.1200/JCO.20.2.514.
    1. Braithwaite D, Emery J, Walter F, Prevost AT, Sutton S. Psychological impact of genetic counseling for familial cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2004;96:122–133. doi: 10.1093/jnci/djh017.
    1. Peshkin BN, DeMarco TA, Brogan BM, Lerman C, Isaacs C. BRCA1/2 testing: complex themes in result interpretation. J Clin Oncol. 2001;19:2555–2565.
    1. Peshkin BN, Isaacs C. Evaluation and management of women with BRCA1/2 mutations. Oncology (Williston Park) 2005;19:1451–1459.
    1. Pieterse AH, Ausems MG, Van Dulmen AM, Beemer FA, Bensing JM. Initial cancer genetic counseling consultation: change in counselees' cognitions and anxiety, and association with addressing their needs and preferences. Am J Med Genet A. 2005;137:27–35.
    1. Rantala J, Platten U, Lindgren G, Nilsson B, Arver B, Lindblom A, Brandberg Y. Risk perception after genetic counseling in patients with increased risk of cancer. Hered Cancer Clin Pract. 2009;7:15. doi: 10.1186/1897-4287-7-15.
    1. Roshanai AH, Rosenquist R, Lampic C, Nordin K. Does enhanced information at cancer genetic counseling improve counselees' knowledge, risk perception, satisfaction and negotiation of information to at-risk relatives?--a randomized study. Acta Oncol. 2009;48:999–1009. doi: 10.1080/02841860903104137.
    1. Meijers-Heijboer H, Brekelmans CT, Menke-Pluymers M, Seynaeve C, Baalbergen A, Burger C, Crepin E, van den Ouweland AW, van Geel B, Klijn JG. Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2003;21:1675–1681. doi: 10.1200/JCO.2003.09.052.
    1. Gronau KA, Semple JL. A guide to establishing the risk for breast cancer in the plastic surgery patient. Ann Plast Surg. 2000;45:554–559. doi: 10.1097/00000637-200045050-00017.
    1. Mitchell G, Ardern-Jones A, Kissin Mchir M, Taylor R, Eeles RA. A paradox: urgent BRCA genetic testing. Fam Cancer. 2001;1:25–29. doi: 10.1023/A:1011570302078.
    1. van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ, Van't Veer LJ, Tollenaar RA. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer. 2005;93:287–292. doi: 10.1038/sj.bjc.6602703.
    1. McDonnell SK, Schaid DJ, Myers JL, Grant CS, Donohue JH, Woods JE, Frost MH, Johnson JL, Sitta DL, Slezak JM, Crotty TB, Jenkins RB, Sellers TA, Hartmann LC. Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. J Clin Oncol. 2001;19:3938–3943.
    1. Herrinton LJ, Barlow WE, Yu O, Geiger AM, Elmore JG, Barton MB, Harris EL, Rolnick S, Pardee R, Husson G, Macedo A, Fletcher SW. Efficacy of prophylactic mastectomy in women with unilateral breast cancer: a cancer research network project. J Clin Oncol. 2005;23:4275–4286. doi: 10.1200/JCO.2005.10.080.
    1. Kurian AW, Sigal BM, Plevritis SK. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol. 2010;28:222–231. doi: 10.1200/JCO.2009.22.7991.
    1. Schwartz MD, Lerman C, Brogan B, Peshkin BN, Isaacs C, DeMarco T, Halbert CH, Pennanen M, Finch C. Utilization of BRCA1/BRCA2 mutation testing in newly diagnosed breast cancer patients. Cancer Epidemiol Biomarkers Prev. 2005;14:1003–1007. doi: 10.1158/1055-9965.EPI-03-0545.
    1. Schwartz MD, Lerman C, Brogan B, Peshkin BN, Halbert CH, DeMarco T, Lawrence W, Main D, Finch C, Magnant C, Pennanen M, Tsangaris T, Willey S, Isaacs C. Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J Clin Oncol. 2004;22:1823–1829. doi: 10.1200/JCO.2004.04.086.
    1. Schlich-Bakker KJ, ten Kroode HF, Ausems MG. A literature review of the psychological impact of genetic testing on breast cancer patients. Patient Educ Couns. 2006;62:13–20. doi: 10.1016/j.pec.2005.08.012.
    1. Schlich-Bakker KJ, Warlam-Rodenhuis CC, van Echtelt J, van den Bout J, Ausems MG, ten Kroode HF. Short term psychological distress in patients actively approached for genetic counselling after diagnosis of breast cancer. Eur J Cancer. 2006;42:2722–2728. doi: 10.1016/j.ejca.2006.05.032.
    1. Schlich-Bakker KJ, Ausems MG, Schipper M, ten Kroode HF, Warlam-Rodenhuis CC, van den Bout J. BRCA1/2 mutation testing in breast cancer patients: a prospective study of the long-term psychological impact of approach during adjuvant radiotherapy. Breast Cancer Res Treat. 2008;109:507–514. doi: 10.1007/s10549-007-9680-y.
    1. Hahn DEE, Bleiker EMA, Aaronson NK, Valdimarsdottir HB, Verhoef S. Experiences with rapid genetic counseling and testing in newly diagnosed breast cancer patients [abstract] Psychooncology. 2006;15:S261.
    1. Frost MH, Slezak JM, Tran NV, Williams CI, Johnson JL, Woods JE, Petty PM, Donohue JH, Grant CS, Sloan JA, Sellers TA, Hartmann LC. Satisfaction after contralateral prophylactic mastectomy: the significance of mastectomy type, reconstructive complications, and body appearance. J Clin Oncol. 2005;23:7849–7856. doi: 10.1200/JCO.2005.09.233.
    1. Geiger AM, West CN, Nekhlyudov L, Herrinton LJ, Liu IL, Altschuler A, Rolnick SJ, Harris EL, Greene SM, Elmore JG, Emmons KM, Fletcher SW. Contentment with quality of life among breast cancer survivors with and without contralateral prophylactic mastectomy. J Clin Oncol. 2006;24:1350–1356. doi: 10.1200/JCO.2005.01.9901.
    1. Tercyak KP, Peshkin BN, Brogan BM, DeMarco T, Pennanen MF, Willey SC, Magnant CM, Rogers S, Isaacs C, Schwartz MD. Quality of life after contralateral prophylactic mastectomy in newly diagnosed high-risk breast cancer patients who underwent BRCA1/2 gene testing. J Clin Oncol. 2007;25:285–291. doi: 10.1200/JCO.2006.07.3890.
    1. Reavey P, McCarthy CM. Update on breast reconstruction in breast cancer. Curr Opin Obstet Gynecol. 2008;20:61–67. doi: 10.1097/GCO.0b013e3282f2329b.
    1. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Methodol. 2001;1:2. doi: 10.1186/1471-2288-1-2.
    1. Couch FJ, DeShano ML, Blackwood MA, Calzone K, Stopfer J, Campeau L, Ganguly A, Rebbeck T, Weber BL. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med. 1997;336:1409–1415. doi: 10.1056/NEJM199705153362002.
    1. The Dutch Association of Comprehensive Cancer Centres - Breast Cancer Guideline 1.1.
    1. Piantadosi S. Clinical Trials: A Methodologic Perspective. New York: John Wiley & Sons; 1997.
    1. Van Riel E, Warlam-Rodenhuis CC, Verhoef S, Rutgers EJ, Ausems MG. BRCA testing of breast cancer patients: medical specialists' referral patterns, knowledge and attitudes to genetic testing. Eur J Cancer Care (Engl) 2010;19:369–376. doi: 10.1111/j.1365-2354.2008.01065.x.
    1. Ardern-Jones A, Kenen R, Eeles R. Too much, too soon? Patients and health professionals' views concerning the impact of genetic testing at the time of breast cancer diagnosis in women under the age of 40. Eur J Cancer Care (Engl) 2005;14:272–281. doi: 10.1111/j.1365-2354.2005.00574.x.
    1. Lerman C, Lustbader E, Rimer B, Daly M, Miller S, Sands C, Balshem A. Effects of individualized breast cancer risk counseling: a randomized trial. J Natl Cancer Inst. 1995;87:286–292. doi: 10.1093/jnci/87.4.286.
    1. Madalinska JB, Hollenstein J, Bleiker E, van Beurden M, Valdimarsdottir HB, Massuger LF, Gaarenstroom KN, Mourits MJ, Verheijen RH, van Dorst EB, van der Putten H, van der Velden K, Boonstra H, Aaronson NK. Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol. 2005;23:6890–6898. doi: 10.1200/JCO.2005.02.626.
    1. Valdimarsdottir HB, Bovbjerg DH, Dash KM, Holland JC, Osborne MP, Miller DG. Psychological distress in women with a familial risk of breast cancer. Psychooncology. 1995;4:133–141. doi: 10.1002/pon.2960040207.
    1. Watson M, Duvivier V, Wade Walsh M, Ashley S, Davidson J, Papaikonomou M, Murday V, Sacks N, Eeles R. Family history of breast cancer: what do women understand and recall about their genetic risk? J Med Genet. 1998;35:731–738. doi: 10.1136/jmg.35.9.731.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. de Bock GH, Bonnema J, Zwaan RE, van de Velde CJ, Kievit J, Stiggelbout AM. Patient's needs and preferences in routine follow-up after treatment for breast cancer. Br J Cancer. 2004;90:1144–1150. doi: 10.1038/sj.bjc.6601655.
    1. Turner J, Kelly B, Swanson C, Allison R, Wetzig N. Psychosocial impact of newly diagnosed advanced breast cancer. Psychooncology. 2005;14:396–407. doi: 10.1002/pon.856.
    1. Spinhoven P, Ormel J, Sloekers PP, Kempen GI, Speckens AE, Van Hemert AM. A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects. Psychol Med. 1997;27:363–370. doi: 10.1017/S0033291796004382.
    1. Horowitz M, Wilner N, Alvarez W. Impact of Event Scale: a measure of subjective stress. Psychosom Med. 1979;41:209–218.
    1. Brom D, Kleber RJ. De Schok Verwerkingslijst [The Impact of Event Scale] Ned Tijdschr Psych. 1985;41:164–168.
    1. Holmes-Rovner M, Kroll J, Schmitt N, Rovner DR, Breer ML, Rothert ML, Padonu G, Talarczyk G. Patient satisfaction with health care decisions: the satisfaction with decision scale. Med Decis Making. 1996;16:58–64. doi: 10.1177/0272989X9601600114.
    1. O'Connor AM. Validation of a decisional conflict scale. Med Decis Making. 1995;15:25–30.
    1. Koedoot N, Molenaar S, Oosterveld P, Bakker P, de Graeff A, Nooy M, Varekamp I, de Haes H. The decisional conflict scale: further validation in two samples of Dutch oncology patients. Patient Educ Couns. 2001;45:187–193. doi: 10.1016/S0738-3991(01)00120-3.
    1. Claes E, Evers-Kiebooms G, Boogaerts A, Decruyenaere M, Denayer L, Legius E. Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients. Am J Med Genet A. 2003;116A:11–19. doi: 10.1002/ajmg.a.10868.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376. doi: 10.1093/jnci/85.5.365.
    1. Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller M, Franzini L, Williams A, de Haes HC, Hopwood P, Cull A, Aaronson NK. The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncol. 1996;14:2756–2768.
    1. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–134. doi: 10.1056/NEJMoa0900212.

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