Abstract
The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node −, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. High RS patients were significantly more likely to follow the treatment suggested by ODX versus low RS patients RR: 1.07 (1.01–1.14). The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.
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References
National Comprehensive Cancer Network (2012) NCCN Clinical practice guidelines in oncology: breast cancer V.1.2012
Oestreicher N, Ramsey SD, Linden HM, McCune JS, van’t Veer LJ, Burke W, Veenstra DL (2005) Gene expression profiling and breast cancer care: what are the potential benefits and policy implications? Genet Med 7(6):380–389. doi:http://www.ncbi.nlm.nih.gov/pubmed/16024969
Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444. doi:10.1016/s0140-6736(11)61625-5
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717. doi:10.1016/s0140-6736(05)66544-0
Griggs JJ, Hawley ST, Graff JJ, Hamilton AS, Jagsi R, Janz NK, Mujahid MS, Friese CR, Salem B, Abrahamse PH, Katz SJ (2012) Factors associated with receipt of breast cancer adjuvant chemotherapy in a diverse population-based sample. J Clin Oncol 30(25):3058–3064. doi:10.1200/JCO.2012.41.9564
Albain KS, Paik S, van’t Veer L (2009) Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays. Breast 18(Suppl 3):S141–S145. doi:10.1016/S0960-9776(09)70290-5
Arpino G, Generali D, Sapino A, Lucia DM, Frassoldati A, de Laurentis M, Paolo P, Mustacchi G, Cazzaniga M, De Placido S, Conte P, Cappelletti M, Zanoni V, Antonelli A, Martinotti M, Puglisi F, Berruti A, Bottini A, Dogliotti L (2013) Gene expression profiling in breast cancer: a clinical perspective. Breast. doi:10.1016/j.breast.2013.01.016
Marchionni L, Wilson RF, Wolff AC, Marinopoulos S, Parmigiani G, Bass EB, Goodman SN (2008) Systematic review: gene expression profiling assays in early-stage breast cancer. Ann Intern Med 148(5):358–369
Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24(23):3726–3734. doi:10.1200/jco.2005.04.7985
Buyse M, Loi S, van’t Veer L, Viale G, Delorenzi M, Glas AM, d’Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98(17):1183–1192. doi:10.1093/jnci/djj329
Kok M, Linn SC, Van Laar RK, Jansen MP, van den Berg TM, Delahaye LJ, Glas AM, Peterse JL, Hauptmann M, Foekens JA, Klijn JG, Wessels LF, Van’t Veer LJ, Berns EM (2009) Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 113(2):275–283. doi:10.1007/s10549-008-9939-y
Genomic Health. Oncotype Dx-Information for patients and caregivers http://www.oncotypedx.com/en-US/Breast/PatientCaregiver/OncoOverview.aspx. Accessed 6 Jun 2012
Sparano JA, Paik S (2008) Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol 26(5):721–728. doi:10.1200/jco.2007.15.1068
Mamounas EP, Tang G, Fisher B, Paik S, Shak S, Costantino JP, Watson D, Geyer CE Jr, Wickerham DL, Wolmark N (2010) Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol 28(10):1677–1683. doi:10.1200/jco.2009.23.7610
Tang G, Shak S, Paik S, Anderson SJ, Costantino JP, Geyer CE Jr, Mamounas EP, Wickerham DL, Wolmark N (2011) Comparison of the prognostic and predictive utilities of the 21-gene recurrence score assay and adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20. Breast Cancer Res Treat 127(1):133–142. doi:10.1007/s10549-010-1331-z
ClinicalTrials.gov (2011) Hormone therapy with or without combination chemotherapy in treating women who have undergone surgery for node-negative breast cancer (The TAILORx Trial). http://www.clinicaltrials.gov/ct2/show/NCT00310180?term=oncotype&rank=3. Accessed 25 Feb 2011
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826. doi:10.1056/NEJMoa041588
Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr (2007) American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25(33):5287–5312. doi:10.1200/JCO.2007.14.2364
Genomic Health. Corporate fact sheet. http://files.shareholder.com/downloads/GHDX/2036901272x0x237157/FFA8A1C1-117B-411E-86A2-FFFDA42F0CFE/FactSheet.pdf.Accessed 25 Aug 2012
Hornberger J, Cosler LE, Lyman GH (2005) Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care 11(5):313–324
Hornberger J, Chien R, Krebs K, Hochheiser L (2011) US Insurance Program’s experience with a multigene assay for early-stage breast cancer. J Oncol Pract 7(3 Suppl):e38s–e45s. doi:10.1200/JOP.2011.000303
Oakman C, Santarpia L, Di Leo A (2010) Breast cancer assessment tools and optimizing adjuvant therapy. Nat Rev Clin Oncol 7(12):725–732. doi:10.1038/nrclinonc.2010.170
Ademuyiwa FO, Miller A, O’Connor T, Edge SB, Thorat MA, Sledge GW, Levine E, Badve S (2011) The effects of oncotype DX recurrence scores on chemotherapy utilization in a multi-institutional breast cancer cohort. Breast Cancer Res Treat 126(3):797–802. doi:10.1007/s10549-010-1329-6
Asad J, Jacobson AF, Estabrook A, Smith SR, Boolbol SK, Feldman SM, Osborne MP, Boachie-Adjei K, Twardzik W, Tartter PI (2008) Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer? Am J Surg 196(4):527–529. doi:10.1016/j.amjsurg.2008.06.021
Geffen DB, Abu-Ghanem S, Sion-Vardy N, Braunstein R, Tokar M, Ariad S, Delgado B, Bayme M, Koretz M (2011) The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy. Ann Oncol 22(11):2381–2386. doi:10.1093/annonc/mdq769
Henry LR, Stojadinovic A, Swain SM, Prindiville S, Cordes R, Soballe PW (2009) The influence of a gene expression profile on breast cancer decisions. J Surg Oncol 99(6):319–323. doi:10.1002/jso.21244
Hornberger J, Chien R, Krebs K, Hochheiser L (2011) US insurance program’s experience with a multigene assay for early-stage breast cancer. Am J Manag Care 17(5 Spec No):e194–202
Joh JE, Esposito NN, Kiluk JV, Laronga C, Lee MC, Loftus L, Soliman H, Boughey JC, Reynolds C, Lawton TJ, Acs PI, Gordan L, Acs G (2011) The effect of Oncotype DX recurrence score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists. Oncologist 16(11):1520–1526. doi:10.1634/theoncologist.2011-0045
Kelly CM, Krishnamurthy S, Bianchini G, Litton JK, Gonzalez-Angulo AM, Hortobagyi GN, Pusztai L (2010) Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor-positive, HER2-normal, grade II, lymph node-negative breast cancers. Cancer 116(22):5161–5167. doi:10.1002/cncr.25269
Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J (2010) Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value Health 13(4):381–387. doi:10.1111/j.1524-4733.2010.00724.x
Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, Kash J, Chew HK, Gaynor ER, Hayes DF, Epstein A, Albain KS (2010) Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 28(10):1671–1676. doi:10.1200/jco.2008.20.2119
Lund MJ, Mosunjac M, Davis KM, Gabram-Mendola S, Rizzo M, Bumpers HL, Hearn S, Zelnak A, Styblo T, O’Regan RM (2012) 21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome. Cancer 118(3):788–796. doi:10.1002/cncr.26180
Oratz R, Paul D, Cohn AL, Sedlacek SM (2007) Impact of a commercial reference laboratory test recurrence score on decision making in early-stage breast cancer. J Oncol Pract 3(4):182–186. doi:10.1200/jop.0742001
Partin JF, Mamounas EP (2011) Impact of the 21-gene recurrence score assay compared with standard clinicopathologic guidelines in adjuvant therapy selection for node-negative, estrogen receptor-positive breast cancer. Ann Surg Oncol 18(12):3399–3406. doi:10.1245/s10434-011-1698-z
Tatarian T, Damle S, McSwain AP, Ojong-Ntui M, Tabbara I, Teal CB (2011) Clinical utility and therapeutic implications of oncotype analysis in patients with breast cancer. Ann Surg Oncol 18:S182
Tzeng JP, Mayer D, Richman AR, Lipkus I, Han PK, Valle CG, Carey LA, Brewer NT (2010) Women’s experiences with genomic testing for breast cancer recurrence risk. Cancer 116(8):1992–2000. doi:10.1002/cncr.24990
Wolf I, Ben-Baruch N, Shapira-Frommer R, Rizel S, Goldberg H, Yaal-Hahoshen N, Klein B, Geffen DB, Kaufman B (2008) Association between standard clinical and pathologic characteristics and the 21-gene recurrence score in breast cancer patients: a population-based study. Cancer 112(4):731–736. doi:10.1002/cncr.23225
Moinuddin I YS, Goodman J (2009) Effect of menopausal status and oncotype recurrence score on treatment choice for early-stage receptor-positive breast cancer. Paper presented at the American Society of Clinical Oncology Breast Cancer Symposium
Guth AA FS, Fei K, Franco R, Bickell N (2011) Utilization of Oncotype DX to predict chemotherapy use in an innercity population. Paper presented at the American Society of Clinical Oncology Annual Meeting
Goodwin MC HJ, Diego M, Frazier TG (2009) Impact of Oncotype DXTM recurrence score and tumor size on making chemotherapy decisions in breast cancer patients. Paper presented at the Sand Antonio Breast Cancer Symposium
Gregg X BT, Rowley B, Rees W (2009) Experience with use of the Oncotype DX gene assay test in a multicenter community-based healthcare system. Paper presented at the San Antonio Breast Cancer Symposium
de Boer RH BC, Speakman D, Mann B (2011) Australian decision impact study: the impact of Oncotype DX recurrence score (RS) on adjuvant treatment decisions in hormone receptor positive (HR+), node negative (N0) and node positive (N+) early stage breast cancer (ESBC) in the multidisciplinary clinic (MDC). Paper presented at the San Antonio Breast Cancer Symposium
Holt S BG, Brinkworth E, Durrani S, Jones S, Khawaja S, Laggner U, Moe M, Pudney D, Pitcher S, Rolles M, Sharaiha Y, Whelan S (2011) Results from a prospective clinical study on the impact of Oncotype DX on adjuvant treatment decision making in a cohort of 142 UK patients. Paper presented at the San Antonio Breast Cancer Symposium
Rezai M EW, Kummel S, Kuhn T, Warm M, Friedrichs K, Schneeweiss A, Markmann S, Eggemann H, Hilfrich J, Jackisch C, Witzel I, Eidtmann H, Kaufmann M, Blohmer JU (2011) Impact of the recurrence score on adjuvant decision-making in ER-positive early breast cancer—results of a large prospective multicentre decision impact study in node negative and node positive disease. Paper presented at the San Antonio Breast Cancer Symposium
Patel H HK, Kaplan C, Davidson R, DeMichele A, Fox KR, Domcheck SM (2007) Utilization of Oncotype DX in node-negative, ER-positive breast cancer patients. Paper presented at the American Society of Clinical Oncology Annual Meeting
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269, W264
Turaga K, Acs G, Laronga C (2010) Gene expression profiling in breast cancer. Cancer Control 17(3):177–182
Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463
Greenland S (1994) Invited commentary: a critical look at some popular meta-analytic methods. Am J Epidemiol 140(3):290–296
Juni P, Witschi A, Bloch R, Egger M (1999) The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 282(11):1054–1060
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2009) Recommendations from the EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer? Genet Med 11(1):66–73. doi:10.1097/GIM.0b013e3181928f56
Marchionni L, Wilson RF, Marinopoulos SS, Wolff AC, Parmigiani G, Bass EB, Goodman SN (2007) Impact of gene expression profiling tests on breast cancer outcomes. Evid Rep Technol Assess (Full Rep) 160:1–105
Dunn L, Demichele A (2009) Genomic predictors of outcome and treatment response in breast cancer. Mol Diagn Ther 13(2):73–90. doi:10.2165/01250444-200913020-00002
Kratz JR, He J, Van Den Eeden SK, Zhu Z-H, Gao W, Pham PT, Mulvihill MS, Ziaei F, Zhang H, Su B, Zhi X, Quesenberry CP, Habel LA, Deng Q, Wang Z, Zhou J, Li H, Huang M-C, Yeh C–C, Segal MR, Ray MR, Jones KD, Raz DJ, Xu Z, Jahan TM, Berryman D, He B, Mann MJ, Jablons DM (2012) A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet 379(9818):823–832. doi:10.1016/s0140-6736(11)61941-7
Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, Beaumont C, Clark-Langone KM, Yoshizawa CN, Lee M, Watson D, Shak S, Kerr DJ (2011) Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol 29(35):4611–4619. doi:10.1200/jco.2010.32.8732
Acknowledgements
Carlson JJ is supported by the Agency for Healthcare Research and Quality Mentored Clinical Scientists Comparative Effectiveness Development Program (K12) at University of Washington (HS019482). Roth JA is supported by a National Institute on Aging T32 (AG027677).
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Carlson, J.J., Roth, J.A. The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Breast Cancer Res Treat 141, 13–22 (2013). https://doi.org/10.1007/s10549-013-2666-z
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DOI: https://doi.org/10.1007/s10549-013-2666-z