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Randomized trial of proactive rapid genetic counseling versus usual care for newly diagnosed breast cancer patients

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Abstract

Purpose

Breast cancer patients who carry BRCA1/BRCA2 gene mutations may consider bilateral mastectomy. Having bilateral mastectomy at the time of diagnosis not only reduces risk of a contralateral breast cancer, but can eliminate the need for radiation therapy and yield improved reconstruction options. However, most patients do not receive genetic counseling or testing at the time of their diagnosis. In this trial, we tested proactive rapid genetic counseling and testing (RGCT) in newly diagnosed breast cancer patients in order to facilitate pre-surgical genetic counseling and testing.

Methods

We recruited newly diagnosed breast cancer patients at increased risk for carrying a BRCA1/2 mutation. Of 379 eligible patients who completed a baseline survey, 330 agreed to randomization in a 2:1 ratio to RGCT (n = 220) versus UC (n = 108). Primary outcomes were genetic counseling and testing uptake and breast cancer surgical decisions.

Results

RGCT led to higher overall (83.8% vs. 54.6%; p < 0.0001) and pre-surgical (57.8% vs. 38.7%; p = 0.001) genetic counseling uptake compared to UC. Despite higher rates of genetic counseling, RGCT did not differ from UC in overall (54.1% vs. 49.1%, p > 0.10) or pre-surgical (30.6% vs. 27.4%, p > 0.10) receipt of genetic test results nor did they differ in uptake of bilateral mastectomy (26.6% vs. 21.8%, p > 0.10).

Conclusions

Although RGCT yielded increased genetic counseling participation, this did not result in increased rates of pre-surgical genetic testing or impact surgical decisions. These data suggest that those patients most likely to opt for genetic testing at the time of diagnosis are being effectively identified by their surgeons.

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References

  1. Whittemore AS, Gong G, John EM et al (2004) Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic Whites. Cancer Epidemiol Biomark Prev 13(12):2078–2083

    CAS  Google Scholar 

  2. Metcalfe K, Lynch HT, Ghadirian P et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22(12):2328–2335. https://doi.org/10.1200/JCO.2004.04.033

    Article  CAS  PubMed  Google Scholar 

  3. Robson M, Svahn T, McCormick B et al (2005) Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series. Cancer 103(1):44–51. https://doi.org/10.1002/cncr.20728

    Article  PubMed  Google Scholar 

  4. Robson ME, Chappuis PO, Satagopan J et al (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6(1):R8–R17. https://doi.org/10.1186/bcr658

    Article  CAS  PubMed  Google Scholar 

  5. Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27(35):5887–5892. https://doi.org/10.1200/JCO.2008.19.9430

    Article  PubMed  Google Scholar 

  6. Malone KE, Begg CB, Haile RW et al (2010) Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol 28(14):2404–2410. https://doi.org/10.1200/JCO.2009.24.2495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Domchek SM, Friebel TM, Singer CF et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304(9):967–975. https://doi.org/10.1001/jama.2010.1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Skytte AB, Cruger D, Gerster M et al (2011) Breast cancer after bilateral risk-reducing mastectomy. Clin Genet 79(5):431–437. https://doi.org/10.1111/j.1399-0004.2010.01604.x

    Article  PubMed  Google Scholar 

  9. Hartmann LC, Schaid DJ, Woods JE et al (1999) Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 340(2):77–84. https://doi.org/10.1056/NEJM199901143400201

    Article  CAS  PubMed  Google Scholar 

  10. Evans DG, Baildam AD, Anderson E et al (2009) Risk reducing mastectomy: outcomes in 10 European centres. J Med Genet 46(4):254–258. https://doi.org/10.1136/jmg.2008.062232

    Article  CAS  PubMed  Google Scholar 

  11. Metcalfe K, Gershman S, Ghadirian P et al (2014) Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ 348:g226. https://doi.org/10.1136/bmj.g226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Francken AB, Schouten PC, Bleiker EM, Linn SC, Rutgers EJ (2013) Breast cancer in women at high risk: the role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies. Breast 22(5):561–568. https://doi.org/10.1016/j.breast.2013.07.045

    Article  PubMed  Google Scholar 

  13. Silva E (2008) Genetic counseling and clinical management of newly diagnosed breast cancer patients at genetic risk for BRCA germline mutations: perspective of a surgical oncologist. Fam Cancer 7(1):91–95. https://doi.org/10.1007/s10689-007-9167-3

    Article  PubMed  Google Scholar 

  14. Yadav S, Reeves A, Campian S, Sufka A, Zakalik D (2017) Preoperative genetic testing impacts surgical decision making in BRCA mutation carriers with breast cancer: a retrospective cohort analysis. Hered Cancer Clin Pract 15:11. https://doi.org/10.1186/s13053-017-0071-z

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lokich E, Stuckey A, Raker C, Wilbur JS, Laprise J, Gass J (2014) Preoperative genetic testing affects surgical decision making in breast cancer patients. Gynecol Oncol 134(2):326–330. https://doi.org/10.1016/j.ygyno.2014.05.028

    Article  PubMed  Google Scholar 

  16. Chiba A, Hoskin TL, Hallberg EJ et al (2016) Impact that timing of genetic mutation diagnosis has on surgical decision making and outcome for BRCA1/BRCA2 mutation carriers with breast cancer. Ann Surg Oncol 23(10):3232–3238. https://doi.org/10.1245/s10434-016-5328-7

    Article  PubMed  PubMed Central  Google Scholar 

  17. Evans DG, Lalloo F, Hopwood P et al (2005) Surgical decisions made by 158 women with hereditary breast cancer aged < 50 years. Eur J Surg Oncol 31(10):1112–1118. https://doi.org/10.1016/j.ejso.2005.05.007

    Article  CAS  PubMed  Google Scholar 

  18. Stolier AJ, Corsetti RL (2005) Newly diagnosed breast cancer patients choose bilateral mastectomy over breast-conserving surgery when testing positive for a BRCA1/2 mutation. Am Surg 71(12):1031–1033

    PubMed  Google Scholar 

  19. Schwartz M, Lerman C, Brogan B et al (2004) Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J Clin Oncol 22(10):1823–1829. https://doi.org/10.1200/JCO.2004.04.086

    Article  PubMed  Google Scholar 

  20. Weitzel JN, McCaffrey SM, Nedelcu R, MacDonald DJ, Blazer KR, Cullinane CA (2003) Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis. Arch Surg 138(12):1323–1328. https://doi.org/10.1001/archsurg.138.12.1323 (discussion 29)

    Article  PubMed  Google Scholar 

  21. Kurian AW, Griffith KA, Hamilton AS et al (2017) Genetic testing and counseling among patients with newly diagnosed breast cancer. JAMA 317(5):531–534. https://doi.org/10.1001/jama.2016.16918

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hafertepen L, Pastorino A, Morman N et al (2017) Barriers to genetic testing in newly diagnosed breast cancer patients: do surgeons limit testing? Am J Surg 214(1):105–110. https://doi.org/10.1016/j.amjsurg.2016.08.012

    Article  PubMed  Google Scholar 

  23. Wevers MR, Aaronson NK, Bleiker EMA et al (2017) Rapid genetic counseling and testing in newly diagnosed breast cancer: patients’ and health professionals’ attitudes, experiences, and evaluation of effects on treatment decision making. J Surg Oncol. https://doi.org/10.1002/jso.24763

    Article  PubMed  Google Scholar 

  24. Weldon CB, Trosman JR, Gradishar WJ, Benson AB 3rd, Schink JC (2012) Barriers to the use of personalized medicine in breast cancer. J Oncol Pract 8(4):e24–e31. https://doi.org/10.1200/JOP.2011.000448

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cortesi L, Razzaboni E, Toss A et al (2014) A rapid genetic counselling and testing in newly diagnosed breast cancer is associated with high rate of risk-reducing mastectomy in BRCA1/2-positive Italian women. Ann Oncol 25(1):57–63. https://doi.org/10.1093/annonc/mdt422

    Article  CAS  PubMed  Google Scholar 

  26. Wevers MR, Aaronson NK, Verhoef S et al (2014) Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial. Br J Cancer 110(4):1081–1087. https://doi.org/10.1038/bjc.2013.805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Berry DA, Iversen ES Jr, Gudbjartsson DF et al (2002) BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol 20(11):2701–2712. https://doi.org/10.1200/JCO.2002.05.121

    Article  CAS  PubMed  Google Scholar 

  28. Schwartz MD, Lerman C, Brogan B et al (2005) Utilization of BRCA1/BRCA2 mutation testing in newly diagnosed breast cancer patients. Cancer Epidemiol Biomark Prev 14(4):1003–1007. https://doi.org/10.1158/1055-9965.EPI-03-0545

    Article  CAS  Google Scholar 

  29. Childers CP, Childers KK, Maggard-Gibbons M, Macinko J (2017) National estimates of genetic testing in women with a history of breast or ovarian cancer. J Clin Oncol 35(34):3800–3806. https://doi.org/10.1200/JCO.2017.73.6314

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kurian AW, Li Y, Hamilton AS et al (2017) Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol 35(20):2232–2239. https://doi.org/10.1200/JCO.2016.71.6480

    Article  PubMed  PubMed Central  Google Scholar 

  31. Delikurt T, Williamson GR, Anastasiadou V, Skirton H (2015) A systematic review of factors that act as barriers to patient referral to genetic services. Eur J Hum Genet 23(6):739–745. https://doi.org/10.1038/ejhg.2014.180

    Article  PubMed  Google Scholar 

  32. Freivogel ME, Cohen SA (2018) Your genes: one size doesn’t fit all. J Natl Compr Canc Netw 16(1):2–3. https://doi.org/10.6004/jnccn.2017.7055

    Article  PubMed  Google Scholar 

  33. Interrante MK, Segal H, Peshkin BN et al (2017) Randomized noninferiority trial of telephone vs in-person genetic counseling for hereditary breast and ovarian cancer: a 12-month follow-up. JNCI Cancer Spectr 1(1):pkx002

    Article  Google Scholar 

  34. Kinney AY, Butler KM, Schwartz MD et al (2014) Expanding access to BRCA1/2 genetic counseling with telephone delivery: a cluster randomized trial. J Natl Cancer Inst. https://doi.org/10.1093/jnci/dju328

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kinney AY, Steffen LE, Brumbach BH et al (2016) Randomized noninferiority trial of telephone delivery of BRCA1/2 genetic counseling compared with in-person counseling: 1-year follow-up. J Clin Oncol 34(24):2914–2924. https://doi.org/10.1200/JCO.2015.65.9557

    Article  PubMed  PubMed Central  Google Scholar 

  36. Schwartz MD, Valdimarsdottir HB, Peshkin BN et al (2014) Randomized noninferiority trial of telephone versus in-person genetic counseling for hereditary breast and ovarian cancer. J Clin Oncol 32(7):618–626. https://doi.org/10.1200/JCO.2013.51.3226

    Article  PubMed  PubMed Central  Google Scholar 

  37. Peshkin BN, Demarco TA, Graves KD et al (2008) Telephone genetic counseling for high-risk women undergoing BRCA1 and BRCA2 testing: rationale and development of a randomized controlled trial. Genet Test 12(1):37–52. https://doi.org/10.1089/gte.2006.0525

    Article  PubMed  Google Scholar 

  38. Peshkin BN, Kelly S, Nusbaum RH et al (2016) Patient perceptions of telephone vs. in-person BRCA1/BRCA2 genetic counseling. J Genet Couns 25(3):472–482. https://doi.org/10.1007/s10897-015-9897-6

    Article  PubMed  Google Scholar 

  39. Jacobs AS, Schwartz MD, Valdimarsdottir H et al (2016) Patient and genetic counselor perceptions of in-person versus telephone genetic counseling for hereditary breast/ovarian cancer. Fam Cancer 15(4):529–539. https://doi.org/10.1007/s10689-016-9900-x

    Article  PubMed  PubMed Central  Google Scholar 

  40. Butrick M, Kelly S, Peshkin BN et al (2015) Disparities in uptake of BRCA1/2 genetic testing in a randomized trial of telephone counseling. Genet Med 17(6):467–475. https://doi.org/10.1038/gim.2014.125

    Article  PubMed  Google Scholar 

  41. Hoberg-Vetti H, Bjorvatn C, Fiane BE et al (2016) BRCA1/2 testing in newly diagnosed breast and ovarian cancer patients without prior genetic counselling: the DNA-BONus study. Eur J Hum Genet 24(6):881–888. https://doi.org/10.1038/ejhg.2015.196

    Article  CAS  PubMed  Google Scholar 

  42. Quinn VF, Meiser B, Kirk J et al (2017) 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 19(4):448–456. https://doi.org/10.1038/gim.2016.130

    Article  PubMed  Google Scholar 

  43. Hughes KS (2017) Genetic testing: what problem are we trying to solve? J Clin Oncol. https://doi.org/10.1200/jco.2017.74.7899

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are grateful to all the women who participated in this study. The authors would like to acknowledge contributions of Drs. Colette Magnant, Elizabeth Feldman and Ms. Tamara Drazin in providing access to their patients. This study was supported by Grants (R01 CA74861 and P30 CA051008) from the National Cancer Institute and by the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Georgetown Lombardi Comprehensive Cancer, Georgetown University, 3300 Whitehaven St., NW, Suite 4100, The Harris Building, Washington, DC, 20007, USA

    Marc D. Schwartz, Beth N. Peshkin, Claudine Isaacs, Shawna Willey, Suzanne O’Neill & Katia Khoury

  2. Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research, Georgetown University, Washington, DC, USA

    Marc D. Schwartz, Beth N. Peshkin, Claudine Isaacs, Shawna Willey & Suzanne O’Neill

  3. Department of Population Health Science and Policy, Center for Behavioral Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Heiddis B. Valdimarsdottir & Lina Jandorf

  4. Department of Psychology, Reykjavik University, Reykjavik, Iceland

    Heiddis B. Valdimarsdottir

  5. School of Medicine, University of Maryland, Baltimore, MD, USA

    Rachel Nusbaum

  6. Concert Genetics, Inc, Franklin, TN, USA

    Gillian Hooker

  7. National Cancer Institute, Bethesda, MD, USA

    Scott P. Kelly

  8. Atlantic Health Services, Carol G. Simon Cancer Center, Summit, NJ, USA

    Jessica Heinzmann

  9. Hackensack University Medical Center, Hackensack, NJ, USA

    Aliza Zidell

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  1. Marc D. Schwartz
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  2. Beth N. Peshkin
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Correspondence to Marc D. Schwartz.

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The authors declare that they have no conflicts of interest.

Ethical standards

This study was approved by the Institutional Review Boards of all participating sites. The study complies with all current laws of the United States of America.

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Schwartz, M.D., Peshkin, B.N., Isaacs, C. et al. Randomized trial of proactive rapid genetic counseling versus usual care for newly diagnosed breast cancer patients. Breast Cancer Res Treat 170, 517–524 (2018). https://doi.org/10.1007/s10549-018-4773-3

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  • DOI: https://doi.org/10.1007/s10549-018-4773-3

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