Gene expression profiling and breast cancer care: What are the potential benefits and policy implications?

Purpose: Gene expression profiling has been proposed as an alternative to clinical guidelines to identify high-risk patients for adjuvant chemotherapy. However, the outcomes associated with gene expression profiling are not clear, and guidelines for the appropriate use of genomic technologies have not been established.Methods: We developed a decision analytic model to evaluate the incremental cost and quality-adjusted life years of gene expression profiling versus NIH clinical guidelines in a hypothetical cohort of premenopausal early stage breast cancer patients 44 years of age. We conducted empirical analyses and identified literature-based data to inform the model, and performed probabilistic sensitivity analyses to evaluate uncertainty in the results. We interpreted the implications of our findings for treatment guidelines and policies.Results: Use of gene expression profiling resulted in an absolute 5% decrease in the proportion of cases of distant recurrence prevented, 0.21 fewer quality-adjusted life years, and a cost savings of $2882. The chosen test cutoff value to identify a tumor as poor prognosis and the cost of adjuvant chemotherapy were the most influential parameters in the analysis, but our findings did not change substantially in sensitivity analyses. Regardless of the test cutoff used to identify a poor prognosis tumor, the gene expression profiling assay studied in our analysis, at its current level of performance, did not attain the threshold sensitivity (95%) necessary to produce equal or greater quality-adjusted life years than NIH guidelines.Conclusion: Although the use of gene expression profiling in breast cancer care holds great promise, our analysis suggests additional refinement and validation are needed before use in clinical practice.

[1]  Roman Rouzier,et al.  Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  R. Bast,et al.  Individualized care for patients with cancer - a work in progress. , 2004, The New England journal of medicine.

[3]  M. Cronin,et al.  A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. , 2004, The New England journal of medicine.

[4]  W. Burke Genetic testing in primary care. , 2004, Annual review of genomics and human genetics.

[5]  H. Bonnefoi,et al.  Clinical trials update of the European Organization for Research and Treatment of Cancer Breast Cancer Group , 2004, Breast Cancer Research.

[6]  N. Oestreicher The economic and clinical outcomes and policy implications of gene expression profiling in breast cancer care , 2004 .

[7]  M. Cronin,et al.  Gene expression profiles of paraffin-embedded core biopsy tissue predict response to chemotherapy in patients with locally advanced breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  J. Hornberger,et al.  Economic analysis of targeting chemotherapy (CT) using a 21 gene RT-PCR assay in lymph node negative (LN-), estrogen receptor positive (ER+) early-stage breast cancer (ESBC). , 2004, Journal of Clinical Oncology.

[9]  Paul Glare,et al.  A systematic review of physicians' survival predictions in terminally ill cancer patients , 2003, BMJ : British Medical Journal.

[10]  Xianglin L. Du,et al.  Discrepancy between Consensus Recommendations and Actual Community Use of Adjuvant Chemotherapy in Women with Breast Cancer , 2003, Annals of Internal Medicine.

[11]  G. Sauter,et al.  Predictive molecular pathology. , 2002, The New England journal of medicine.

[12]  Jeffery R. Botkin,et al.  Genetics in Primary Care: A USA Faculty Development Initiative , 2002, Public Health Genomics.

[13]  Jon Emery,et al.  Genetics education for primary-care providers , 2002, Nature Reviews Genetics.

[14]  Ahmedin Jemal,et al.  Annual Report to the Nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden , 2002, Cancer.

[15]  L. Clegg,et al.  Adjuvant therapy for breast cancer: practice patterns of community physicians. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[17]  P. Ravdin,et al.  Decision-making in early breast cancer: guidelines and decision tools. , 2002, European journal of cancer.

[18]  M. Fay,et al.  Costs of treatment for elderly women with early-stage breast cancer in fee-for-service settings. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Van,et al.  A gene-expression signature as a predictor of survival in breast cancer. , 2002, The New England journal of medicine.

[20]  Jared Bernstein,et al.  The State of Working America, 2002/2003 , 2005 .

[21]  R. Simes,et al.  Patient preferences for adjuvant chemotherapy of early breast cancer: how much benefit is needed? , 2001, Journal of the National Cancer Institute. Monographs.

[22]  A. Sinha,et al.  Gene expression profile analysis by DNA microarrays: promise and pitfalls. , 2001, JAMA.

[23]  Robert J. Mayer,et al.  National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000. , 2001, Journal of the National Cancer Institute.

[24]  C. Shapiro,et al.  Side effects of adjuvant treatment of breast cancer. , 2001, The New England journal of medicine.

[25]  D. Buist,et al.  Cost comparison of mastectomy versus breast-conserving therapy for early-stage breast cancer. , 2001, Journal of the National Cancer Institute.

[26]  R. Bast,et al.  2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  P. Ravdin,et al.  Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  C. Loprinzi,et al.  Understanding the utility of adjuvant systemic therapy for primary breast cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  M Markman,et al.  National Institutes of Health Consensus Development Conference statement: adjuvant therapy for breast cancer, November 1-3, 2000. , 2001, Journal of the National Cancer Institute. Monographs.

[30]  E. Winer,et al.  NCCN Practice Guidelines for Breast Cancer. , 2000, Oncology.

[31]  E. Winer,et al.  Update: NCCN practice guidelines for the treatment of breast cancer. National Comprehensive Cancer Network. , 1999, Oncology.

[32]  Mike Clarke,et al.  Polychemotherapy for early breast cancer: an overview of the randomised trials , 1998, The Lancet.

[33]  M. Mcgrath Cost Effectiveness in Health and Medicine. , 1998 .

[34]  L. Lenert,et al.  Incorporating Risk Attitude into Markov-process Decision Models: , 1997, Medical decision making : an international journal of the Society for Medical Decision Making.

[35]  E. Feuer,et al.  Estimating medical costs from incomplete follow-up data. , 1997, Biometrics.

[36]  J. Hayman,et al.  Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  C. Somkin,et al.  Cost of Care for Cancer in a Health Maintenance Organization , 1997, Health care financing review.

[38]  J. Lokich,et al.  Comparison of costs for infusion versus bolus chemotherapy administration‐‐Part two: Use of charges versus reimbursement for cost basis , 1996 .

[39]  L. Kessler,et al.  Medicare Payments from Diagnosis to Death for Elderly Cancer Patients by Stage at Diagnosis , 1995, Medical care.

[40]  N Urban,et al.  Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care. , 1995, Journal of the National Cancer Institute.

[41]  P. Novotny,et al.  Do American oncologists know how to use prognostic variables for patients with newly diagnosed primary breast cancer? , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  P. Novotny,et al.  Prospective evaluation of prognostic variables from patient-completed questionnaires. North Central Cancer Treatment Group. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  P. Ravdin A practical view of prognostic factors for staging, adjuvant treatment planning, and as baseline studies for possible future therapy. , 1994, Hematology/oncology clinics of North America.

[44]  C. Shapiro,et al.  Late effects of adjuvant therapy for breast cancer. , 1994, Journal of the National Cancer Institute. Monographs.

[45]  J R Beck,et al.  Markov Models in Medical Decision Making , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[46]  B. Hillner,et al.  The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  W. McGuire,et al.  Prognosis and treatment decisions in patients with breast cancer without axillary node involvement , 1992, Cancer.

[48]  J. Richardson,et al.  A cost utility analysis of mammography screening in Australia. , 1992, Social science & medicine.

[49]  B. Hillner,et al.  Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer. Estimates using decision analysis while awaiting clinical trial results. , 1992, JAMA.

[50]  Harry J. de Koning,et al.  The impact of a breast cancer screening programme on quality‐adjusted life‐years , 1991, International journal of cancer.

[51]  B E Hillner,et al.  Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. A decision-analysis model. , 1991, The New England journal of medicine.

[52]  L. Siminoff,et al.  Factors affecting treatment decisions for a life-threatening illness: the case of medical treatment of breast cancer. , 1991, Social science & medicine.

[53]  S. Piantadosi,et al.  Effect of patients' expectations of benefit with standard breast cancer adjuvant chemotherapy on participation in a randomized clinical trial: a clinical vignette study. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[54]  L. Siminoff,et al.  Effects of outcome framing on treatment decisions in the real world: impact of framing on adjuvant breast cancer decisions. , 1989, Medical decision making : an international journal of the Society for Medical Decision Making.

[55]  S. Wilson Methods for the economic evaluation of health care programmes , 1987 .

[56]  B. McNeil,et al.  Probabilistic Sensitivity Analysis Using Monte Carlo Simulation , 1985, Medical decision making : an international journal of the Society for Medical Decision Making.

[57]  C N Smart,et al.  The incidence and economic costs of cancer, motor vehicle injuries, coronary heart disease, and stroke: a comparative analysis. , 1980, American journal of public health.