A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer

Key Points Question Is unselected genetic testing of all women with breast cancer cost-effective compared with testing based on clinical criteria or family history? Findings In this cost-effectiveness microsimulation modeling study incorporating data from 11 836 women, unselected BRCA1/BRCA2/PALB2 testing at breast cancer diagnosis was extremely cost-effective compared with BRCA1/BRCA2 testing based on clinical criteria or family history for UK and US health systems, with incremental cost-effectiveness ratios of £10 464 or £7216 and $65 661 or $61 618 per quality-adjusted life-year, respectively. One year’s unselected panel genetic testing could prevent 2101 cases of breast or ovarian cancer and 633 deaths in the United Kingdom and 9733 cases and 2406 deaths in the United States. Meaning These findings support changing current policy to expand genetic testing to all women with breast cancer.

[1]  Justin Mills,et al.  Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer. , 2020, American family physician.

[2]  B. Karlan,et al.  International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation , 2019, British Journal of Cancer.

[3]  Rakesh R. Patel,et al.  Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle? , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Gabe S. Sonke,et al.  Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer , 2018, The New England journal of medicine.

[5]  R. Manchanda,et al.  Population Based Testing for Primary Prevention: A Systematic Review , 2018, Cancers.

[6]  S. Manley,et al.  Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing , 2018, JAMA.

[7]  M. Vikkula,et al.  Prevalence of pathogenic variants and variants of unknown significance in patients at high risk of breast cancer: A systematic review and meta-analysis of gene-panel data. , 2018, Critical reviews in oncology/hematology.

[8]  Jack Cuzick,et al.  Long-term Accuracy of Breast Cancer Risk Assessment Combining Classic Risk Factors and Breast Density , 2018, JAMA oncology.

[9]  V. S. Gordeev,et al.  Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population , 2018, Journal of Medical Genetics.

[10]  E. Schlichting,et al.  BRCA mutation carrier detection. A model-based cost-effectiveness analysis comparing the traditional family history approach and the testing of all patients with breast cancer , 2018, ESMO Open.

[11]  David Evans,et al.  Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study , 2018, The Lancet. Oncology.

[12]  Cost-effectiveness analysis of germ-line BRCA testing in women with breast cancer and cascade testing in family members of mutation carriers , 2018, Genetics in Medicine.

[13]  Amanda E Lamb,et al.  Examination of the Patient-Focused Impact of Cancer Telegenetics Among a Rural Population: Comparison with Traditional In-Person Services. , 2017, Telemedicine journal and e-health : the official journal of the American Telemedicine Association.

[14]  Charis Eng,et al.  Impact of an embedded genetic counselor on breast cancer treatment , 2018, Breast Cancer Research and Treatment.

[15]  L. Senter,et al.  Genetic consultation embedded in a gynecologic oncology clinic improves compliance with guideline-based care. , 2017, Gynecologic oncology.

[16]  K. Hughes Genetic Testing: What Problem Are We Trying to Solve? , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  C. Childers,et al.  National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  E. Arias,et al.  United States Life Tables, 2014. , 2017, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[19]  M. Munsell,et al.  A universal genetic testing initiative for patients with high-grade, non-mucinous epithelial ovarian cancer and the implications for cancer treatment. , 2017, Gynecologic oncology.

[20]  W. Chung,et al.  Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers , 2017, JAMA.

[21]  R. Jagsi,et al.  Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  S. Buys,et al.  Randomized Noninferiority Trial of Telephone Delivery of BRCA1/2 Genetic Counseling Compared With In-Person Counseling: 1-Year Follow-Up. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  Suzanne Miller,et al.  New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study , 2016, Journal of Medical Genetics.

[24]  J. Wardle,et al.  Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations , 2016, Journal of Medical Genetics.

[25]  S. Seal,et al.  Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients , 2016, Scientific Reports.

[26]  S. Narod,et al.  Genetic risk assessment and prevention: the role of genetic testing panels in breast cancer , 2015, Expert review of anticancer therapy.

[27]  Nazneen Rahman,et al.  Gene-panel sequencing and the prediction of breast-cancer risk. , 2015, The New England journal of medicine.

[28]  Jinbo Chen,et al.  RE: Breast Cancer Risk After Salpingo-Oophorectomy in Healthy BRCA1/2 Mutation Carriers: Revisiting the Evidence for Risk Reduction. , 2015, Journal of the National Cancer Institute.

[29]  Giovanni Parmigiani,et al.  Recent Enhancements to the Genetic Risk Prediction Model BRCAPRO , 2015, Cancer informatics.

[30]  J. Wardle,et al.  Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial , 2014, Journal of the National Cancer Institute.

[31]  H. Meijers-Heijboer,et al.  Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. , 2015, Journal of the National Cancer Institute.

[32]  Karla Bowles,et al.  Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next‐generation sequencing with a 25‐gene panel , 2015, Cancer.

[33]  M. Cowie National Institute for Health and Care Excellence. , 2015, European heart journal.

[34]  S. Buys,et al.  Expanding access to BRCA1/2 genetic counseling with telephone delivery: a cluster randomized trial. , 2014, Journal of the National Cancer Institute.

[35]  Joshua T. Cohen,et al.  Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold. , 2014, The New England journal of medicine.

[36]  Nazneen Rahman,et al.  Breast-cancer risk in families with mutations in PALB2. , 2014, The New England journal of medicine.

[37]  J. Garber,et al.  Randomized noninferiority trial of telephone versus in-person genetic counseling for hereditary breast and ovarian cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  Rongwei Fu,et al.  Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation , 2014, Annals of Internal Medicine.

[39]  A. Howell,et al.  Breast cancer risk assessment in 8,824 women attending a family history evaluation and screening programme , 2013, Familial Cancer.

[40]  Joseph A Hill United States Life Tables , 2013 .

[41]  E. Rutgers,et al.  Breast cancer in women at high risk: the role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies. , 2013, Breast.

[42]  A. LaCroix,et al.  Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data , 2013, The Lancet.

[43]  J. Manson,et al.  Long-Term Mortality Associated With Oophorectomy Compared With Ovarian Conservation in the Nurses' Health Study , 2013, Obstetrics and gynecology.

[44]  J. Billeter Long term Conditions Compendium of Information , 2013 .

[45]  M. Yaffe,et al.  Long-term results of screening with magnetic resonance imaging in women with BRCA mutations , 2012, British Journal of Cancer.

[46]  D. Oram,et al.  Factors influencing uptake and timing of risk reducing salpingo‐oophorectomy in women at risk of familial ovarian cancer: a competing risk time to event analysis , 2012, BJOG : an international journal of obstetrics and gynaecology.

[47]  K. Sandelin,et al.  Less correspondence between expectations before and cosmetic results after risk-reducing mastectomy in women who are mutation carriers: a prospective study. , 2012, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[48]  K. Sandelin,et al.  High satisfaction rate ten years after bilateral prophylactic mastectomy - a longitudinal study. , 2011, European Journal of Cancer Care.

[49]  D. Oram,et al.  Outcome of risk‐reducing salpingo‐oophorectomy in BRCA carriers and women of unknown mutation status , 2011, BJOG : an international journal of obstetrics and gynaecology.

[50]  B. Rosen,et al.  The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation. , 2011, Gynecologic oncology.

[51]  Rosalind Eeles,et al.  Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. , 2010, JAMA.

[52]  J. Dungan Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses' Health Study , 2010 .

[53]  A. Howell,et al.  Uptake of Risk-Reducing Surgery in Unaffected Women at High Risk of Breast and Ovarian Cancer Is Risk, Age, and Time Dependent , 2009, Cancer Epidemiology, Biomarkers & Prevention.

[54]  J. Manson,et al.  Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses’ Health Study , 2009, Obstetrics and gynecology.

[55]  Susan M. Domchek,et al.  Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-oophorectomy in BRCA1 or BRCA2 Mutation Carriers , 2009, Journal of the National Cancer Institute.

[56]  Walter A. Rocca,et al.  Increased cardiovascular mortality after early bilateral oophorectomy , 2009, Menopause.

[57]  L. Shulman Increased cardiovascular mortality after early bilateral oophorectomy , 2009 .

[58]  A. Spurdle,et al.  Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results , 2008, Human mutation.

[59]  N. Loman,et al.  Aesthetic outcome, patient satisfaction, and health-related quality of life in women at high risk undergoing prophylactic mastectomy and immediate breast reconstruction. , 2008, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[60]  Annika Lindblom,et al.  Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  J. Hopper,et al.  The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions , 2008, British Journal of Cancer.

[62]  Jan Lubinski,et al.  International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers , 2008, International journal of cancer.

[63]  H A Risch,et al.  The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions , 2008, British Journal of Cancer.

[64]  P. Loehrer Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation , 2008 .

[65]  P. Møller,et al.  Genetic epidemiology of BRCA mutations--family history detects less than 50% of the mutation carriers. , 2007, European journal of cancer.

[66]  L. Esserman,et al.  Genetic/familial high-risk assessment , 2010 .

[67]  F. Couch,et al.  Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. , 2006, JAMA.

[68]  F. Eugene Yates,et al.  The national center for health statistics , 1973, Annals of Biomedical Engineering.

[69]  N. Aaronson,et al.  Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[70]  A R Padhani,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) , 2005, The Lancet.

[71]  Andrew Briggs,et al.  Probabilistic analysis of cost-effectiveness models: statistical representation of parameter uncertainty. , 2005, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[72]  Susan L Neuhausen,et al.  Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  J. Witte,et al.  Comparison of missing data approaches in linkage analysis , 2003, BMC Genetics.

[74]  M. Khoury,et al.  Human Genome Epidemiology: A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease , 2003 .

[75]  Stefan Wagenpfeil,et al.  Validation of health economic models: the example of EVITA. , 2003, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[76]  Peter A Ubel,et al.  What is the price of life and why doesn't it increase at the rate of inflation? , 2003, Archives of internal medicine.

[77]  Carol L. Brown,et al.  Quality of life in women at risk for ovarian cancer who have undergone risk-reducing oophorectomy. , 2003, Gynecologic oncology.

[78]  C. Seynaeve,et al.  Clinical experience of prophylactic mastectomy followed by immediate breast reconstruction in women at hereditary risk of breast cancer (HB(O)C) or a proven BRCA1 and BRCA2 germ-line mutation. , 2002, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[79]  G. Giles,et al.  Design and analysis issues in a population-based, case-control-family study of the genetic epidemiology of breast cancer and the Co-operative Family Registry for Breast Cancer Studies (CFRBCS). , 1999, Journal of the National Cancer Institute. Monographs.