The impact of gene expression profile testing on confidence in chemotherapy decisions and prognostic expectations
Little is known about whether gene expression profile (GEP) testing and specific recurrence scores (e.g., medium risk) improve women’s confidence in their chemotherapy decision or perceived recurrence risk. We evaluate the relationship between these outcomes and GEP testing.
We surveyed women eligible for GEP testing (stage I or II, Gr1-2, ER+, HER2−) identified through the Surveillance, Epidemiology, and End Results (SEER) Registry of Washington or Kaiser Permanente Northern California from 2012 to 2016, approximately 0–4 years from diagnosis (N = 904, RR = 45.4%). Confidence in chemotherapy was measured as confident (Very, completely) versus Not Confident (Somewhat, A little, Not At All); perceived risk recurrence was recorded numerically (0–100%). Women reported their GEP test receipt (Yes, No, Unknown) and risk recurrence score (High, Intermediate, Low, Unknown). In our analytic sample (N = 833), we propensity score weighted the three test receipt cohorts and used propensity weighted multivariable regressions to examine associations between the outcomes and the three test receipt cohorts, with receipt stratified by score.
29.5% reported an unknown GEP test receipt; 86% being confident. Compared to no test receipt, an intermediate score (aOR 0.34; 95% CI 0.20–0.58), unknown score (aOR 0.09; 95% CI 0.05–0.18), and unknown test receipt (aOR 0.37; 95% CI 0.24–0.57) were less likely to report confidence. Most women greatly overestimated their recurrence risk regardless of their test receipt or score.
GEP testing was not associated with greater confidence in chemotherapy decisions. Better communication about GEP testing and the implications for recurrence risk may improve women’s decisional confidence.
KeywordsGene expression profile testing Breast cancer Chemotherapy
We appreciate the contributions of the KPNC Research Team, including Yan Li, MD, Laurel Habel, PhD, Stephanie Prausnitz, MS, Tom Ray, MBA, and Alice Ansfield, Pete Bogdanos, and Lillian Pacheco.
This research was supported by National Cancer Institute Grant #UO1 CA183081 (to JM, TL, and SR). This work was also supported, in part, by Grant #U01 CA152958 from the National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network (CISNET), Grant #R35CA197289 (to JM) from the National Cancer Institute, Grant #UC2 CA148471 (to Katrina Goddard, Lawrence Kushi, and Evelyn Whitlock) from the National Cancer Institute, R01 CA105274 (to Lawrence Kushi) from the National Cancer Institute, and a supplement to Grant # UO1 CA183081 from the National Cancer Institute (SCO), Georgetown-Lombardi American Cancer Society Young Investigator Award (ACS IRG 92-152-20) and the Cancer Prevention Research Fellowship sponsored by the American Society of Preventive Oncology and Breast Cancer Research Foundation (ASPO-17-001) (to Jinani Jayasekera). The content is solely the responsibility of the authors and does not represent the official views of the National Cancer Institute at the National Institutes of Health.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.National Cancer Comprehensive Network® (2018) NCCN guideline with NCCN Evidence Blocks™—breast cancer version 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed 14 May 2018
- 2.Harris LN, Ismaila N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM, Hammond EH, Kuderer NM, Liu MC, Mennel RG, Van Poznak C, Bast RC, Hayes DF (2016) Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol Off J Am Soc Clin Oncol 34(10):1134–1150. https://doi.org/10.1200/jco.2015.65.2289 CrossRefGoogle Scholar
- 3.Krop I, Ismaila N, Stearns V (2017) Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice focused update guideline summary. J Oncol Pract 13(11):763–766. https://doi.org/10.1200/jop.2017.024646 CrossRefPubMedGoogle Scholar
- 4.Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, Olson JA Jr, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373(21):2005–2014. https://doi.org/10.1056/NEJMoa1510764 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr (2018) Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa1804710 PubMedPubMedCentralGoogle Scholar
- 6.Genomic Health, Inc. Oncotype DX: essential genomic information for improving your treatment decision. http://www.mybreastcancertreatment.org/en-US/LearnAboutOncotypeDX/WhatIsOncotypeDXForBreastCancer.aspx. Accessed 14 May 2018
- 7.Agendia, Inc. Know your breast Cancer.com: personalized genomic testing with MammaPrint®. http://knowyourbreastcancer.com/. Accessed 14 May 2018
- 8.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 Off J Am Soc Clin Oncol 28(10):1671–1676. https://doi.org/10.1200/jco.2008.20.2119 CrossRefGoogle Scholar
- 11.Sulayman N, Spellman E, Graves KD, Peshkin BN, Isaacs C, Schwartz MD, O’Neill SC (2012) Psychosocial and quality of life in women receiving the 21-gene recurrence score assay: the impact of decision style in women with intermediate RS. J Cancer Epidemiol 2012:728290. https://doi.org/10.1155/2012/728290 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Lieu TA, Ray GT, Prausnitz SR, Habel LA, Alexeeff S, Li Y, Ramsey SD, Phelps CE, Chawla N, O’Neill SC Mandelblatt JS (2017) Oncologist and organizational factors associated with variation in breast cancer multigene testing. Breast Cancer Res Treat 163(1):167–176. https://doi.org/10.1007/s10549-017-4158-z CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Chandler Y, Schechter CB, Jayasekera J, Near A, O’Neill SC, Isaacs C, Phelps CE, Ray GT, Lieu TA, Ramsey S, Mandelblatt JS (2018) Cost effectiveness of gene expression profile testing in community practice. J Clin Oncol Off J Am Soc Clin Oncol 36(6):554–562. https://doi.org/10.1200/jco.2017.74.5034 CrossRefGoogle Scholar
- 16.Hawley ST, Janz NK, Griffith KA, Jagsi R, Friese CR, Kurian AW, Hamilton AS, Ward KC, Morrow M, Wallner LP, Katz SJ (2017) Recurrence risk perception and quality of life following treatment of breast cancer. Breast Cancer Res Treat 161(3):557–565. https://doi.org/10.1007/s10549-016-4082-7 CrossRefPubMedGoogle Scholar
- 20.Spreeuwenberg MD, Bartak A, Croon MA, Hagenaars JA, Busschbach JJ, Andrea H, Twisk J, Stijnen T (2010) The multiple propensity score as control for bias in the comparison of more than two treatment arms: an introduction from a case study in mental health. Med Care 48(2):166–174. https://doi.org/10.1097/MLR.0b013e3181c1328f CrossRefPubMedGoogle Scholar
- 21.Partridge A, Adloff K, Blood E, Dees EC, Kaelin C, Golshan M, Ligibel J, de Moor JS, Weeks J, Emmons K, Winer E (2008) Risk perceptions and psychosocial outcomes of women with ductal carcinoma in situ: longitudinal results from a cohort study. J Natl Cancer Inst 100(4):243–251. https://doi.org/10.1093/jnci/djn010 CrossRefPubMedGoogle Scholar
- 22.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. https://doi.org/10.1634/theoncologist.2011-0045 CrossRefPubMedPubMedCentralGoogle Scholar
- 23.O’Neill SC, Isaacs C, Lynce F, Graham DM, Chao C, Sheppard VB, Zhou Y, Liu C, Selvam N, Schwartz MD, Potosky AL (2017) Endocrine therapy initiation, discontinuation and adherence and breast imaging among 21-gene recurrence score assay-eligible women under age 65. Breast Cancer Res 19(1):45. https://doi.org/10.1186/s13058-017-0837-2 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Hassett MJ, Silver SM, Hughes ME, Blayney DW, Edge SB, Herman JG et al (2012) Adoption of gene expression profile testing and association with use of chemotherapy among women with breast cancer. J Clin Oncol 30(18):2218–2226. https://doi.org/10.1200/JCO.2011.38.5740 CrossRefPubMedPubMedCentralGoogle Scholar