Metastatic breast cancer patient perceptions of somatic tumor genomic testing

Elizabeth J Adams, Sarah Asad, Raquel Reinbolt, Katharine A Collier, Mahmoud Abdel-Rasoul, Susan Gillespie, James L Chen, Mathew A Cherian, Anne M Noonan, Sagar Sardesai, Jeffrey VanDeusen, Robert Wesolowski, Nicole Williams, Charles L Shapiro, Erin R Macrae, Robert Pilarski, Amanda E Toland, Leigha Senter, Bhuvaneswari Ramaswamy, Clara N Lee, Maryam B Lustberg, Daniel G Stover, Elizabeth J Adams, Sarah Asad, Raquel Reinbolt, Katharine A Collier, Mahmoud Abdel-Rasoul, Susan Gillespie, James L Chen, Mathew A Cherian, Anne M Noonan, Sagar Sardesai, Jeffrey VanDeusen, Robert Wesolowski, Nicole Williams, Charles L Shapiro, Erin R Macrae, Robert Pilarski, Amanda E Toland, Leigha Senter, Bhuvaneswari Ramaswamy, Clara N Lee, Maryam B Lustberg, Daniel G Stover

Abstract

Background: To assess metastatic breast cancer (MBC) patient psychological factors, perceptions, and comprehension of tumor genomic testing.

Methods: In a prospective, single institution, single-arm trial, patients with MBC underwent next-generation sequencing at study entry with sequencing results released at progression. Patients who completed surveys before undergoing sequencing were included in the present secondary analysis (n = 58). We administered four validated psychosocial measures: Center for Epidemiologic Studies Depression Scale, Beck Anxiety Inventory, Trust in Physician Scale, and Communication and Attitudinal Self-Efficacy scale for Cancer. Genetic comprehension was assessed using 7-question objective and 6-question subjective measures. Longitudinal data were assessed (n = 40) using paired Wilcoxon signed rank and McNemar's test of agreement.

Results: There were no significant differences between the beginning and end of study in depression, anxiety, physician trust, or self-efficacy (median time on study: 7.6 months). Depression and anxiety were positively associated with each other and both negatively associated with self-efficacy. Self-efficacy decreased from pre- to post-genomic testing (p = 0.05). Objective genetics comprehension did not significantly change from pre- to post-genomic testing, but patients expressed increased confidence in their ability to teach others about genetics (p = 0.04). Objective comprehension was significantly lower in non-white patients (p = 0.02) and patients with lower income (p = 0.04).

Conclusions: This is the only study, to our knowledge, to longitudinally evaluate multiple psychological metrics in MBC as patients undergo tumor genomic testing. Overall, psychological dimensions remained stable over the duration of tumor genomic testing. Among patients with MBC, depression and anxiety metrics were negatively correlated with patient self-efficacy. Patients undergoing somatic genomic testing had limited genomic knowledge, which varied by demographic groups and may warrant additional educational intervention.

Clinical trial information: NCT01987726, registered November 13, 2013.

Keywords: Genomics; Metastatic breast cancer.

Conflict of interest statement

The funding sources for the study, including Foundation Medicine, Inc., were not involved in the collection, analysis, or interpretation of the data. RW has received research support from Acerta and Astra Zeneca and served on advisory boards for PUMA and Pfizer. Drs. Stover, Lustberg, and Lee had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Figures

Fig. 1
Fig. 1
CONSORT Diagram
Fig. 2
Fig. 2
Assessment and Change in Validated Psychological Metrics. Four validated psychosocial measures were assessed in patients at study entry: Center for Epidemiologic Studies Depression Scale (CES-D) [23], Beck Anxiety Inventory (BAI) [24], Trust in Physicians/Providers Scale (TPS) [25], and Communication and Attitudinal Self-Efficacy scale for cancer (CASE-cancer) [26]. a. Change in each measure was evaluated for those patients who completed both ‘pre’ and ‘post’ assessments (n = 40 patients). Direction of change in score is indicated in color as decrease (red), increase (green), and no change (blue). Association was assessed by Wilcoxon signed rank test. b/c. Correlation between patients’ scores on each validated metric and all other assessed metrics was assessed at study entry (b;n = 58 patients) and at end of study (c; n = 40 patients). Direction correlation (Pearson’s r) is indicated by the color of each dot (positive correlation in blue, negative correlation in red) and magnitude of correlation indicated by size of each dot (higher correlation is larger size). Associations that were not statistically significant are indicated with a black ‘x’
Fig. 3
Fig. 3
Patient Objective Genetic Knowledge Assessment. Participants completed a seven-question objective genetic knowledge survey at study entry and ‘genetic knowledge score’ assessed as percentage correct. a. Association of genetic knowledge score with demographic features including income (top left panel), race (top right), education (bottom left), and insurance type (bottom right). Test of association by ANOVA test indicated with p-value. b. Change in genetic knowledge score from study entry (‘Pre-test’) to end of study (‘Post-test). Association was assessed by Wilcoxon signed rank test

References

    1. Mariotto AB, Etzioni R, Hurlbert M, et al. Estimation of the number of women living with metastatic breast Cancer in the United States. Cancer Epidemiol Biomark Prev. 2017;26:809–815. doi: 10.1158/1055-9965.EPI-16-0889.
    1. Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast Cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2:1310–1315. doi: 10.1001/jamaoncol.2016.1279.
    1. Fribbens C, O'Leary B, Kilburn L, et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast Cancer. J Clin Oncol. 2016;34:2961–2968. doi: 10.1200/JCO.2016.67.3061.
    1. Razavi P, Chang MT, Xu G, et al. The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers. Cancer Cell. 2018;34:427–438 e6. doi: 10.1016/j.ccell.2018.08.008.
    1. Condorelli R, Mosele F, Verret B, et al. Genomic alterations in breast cancer: level of evidence for actionability according to ESMO scale for clinical Actionability of molecular targets (ESCAT). Ann Oncol. 2019.
    1. Andre F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380:1929–1940. doi: 10.1056/NEJMoa1813904.
    1. Arnedos M, Vicier C, Loi S, et al. Precision medicine for metastatic breast cancer--limitations and solutions. Nat Rev Clin Oncol. 2015;12:693–704. doi: 10.1038/nrclinonc.2015.123.
    1. Dancey JE, Bedard PL, Onetto N, et al. The genetic basis for cancer treatment decisions. Cell. 2012;148:409–420. doi: 10.1016/j.cell.2012.01.014.
    1. Cheng DT, Mitchell TN, Zehir A, et al. Memorial Sloan Kettering-integrated mutation profiling of actionable Cancer targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251–264. doi: 10.1016/j.jmoldx.2014.12.006.
    1. Russnes HG, Navin N, Hicks J, et al. Insight into the heterogeneity of breast cancer through next-generation sequencing. J Clin Invest. 2011;121:3810–3818. doi: 10.1172/JCI57088.
    1. Chin L, Andersen JN, Futreal PA. Cancer genomics: from discovery science to personalized medicine. Nat Med. 2011;17:297–303. doi: 10.1038/nm.2323.
    1. Berg JS, Khoury MJ, Evans JP. Deploying whole genome sequencing in clinical practice and public health: meeting the challenge one bin at a time. Genet Med. 2011;13:499–504. doi: 10.1097/GIM.0b013e318220aaba.
    1. Gray SW, Park ER, Najita J, et al. Oncologists' and cancer patients' views on whole-exome sequencing and incidental findings: results from the CanSeq study. Genet Med. 2016;18:1011–1019. doi: 10.1038/gim.2015.207.
    1. Miller FA, Hayeems RZ, Bytautas JP, et al. Testing personalized medicine: patient and physician expectations of next-generation genomic sequencing in late-stage cancer care. Eur J Hum Genet. 2014;22:391–395. doi: 10.1038/ejhg.2013.158.
    1. Gray SW, Hicks-Courant K, Lathan CS, et al. Attitudes of patients with cancer about personalized medicine and somatic genetic testing. J Oncol Pract. 2012;8:329–335. doi: 10.1200/JOP.2012.000626.
    1. Liang R, Meiser B, Smith S, Kasparian NA, Lewis CR, et al. Advanced cancer patients’ attitudes towards, and experiences with, screening for somatic mutations in tumours: a qualitative study. Eur J Cancer Care. 2016:1–11. .
    1. Pellegrini I, Rapti M, Extra JM, et al. Tailored chemotherapy based on tumour gene expression analysis: breast cancer patients' misinterpretations and positive attitudes. Eur J Cancer Care (Engl) 2012;21:242–250. doi: 10.1111/j.1365-2354.2011.01300.x.
    1. Foundation Medicine Inc. FM. 2018. . Accessed 28 Nov 2018.
    1. Stover DG, Reinbolt RE, Adams EJ, Asad S, Tolliver K, Abdel-Rasoul M, Timmers CD, Gillespie S, Chen JL, Ali SM, Webster J, Collier KA, Cherian MA, Noonan AM, Sardesai S, VanDeusen J, Wesolowski R, Williams N, Lee CN, Shapiro CL, Macrae ER, Ramaswamy B, Lustberg MB. Prospective Decision-Analysis Study of Clinical Genomic Testing in Metastatic Breast Cancer: Impact on Outcomes and Patient Perceptions. JCO Precision Oncol. 2019:1–11. .
    1. Arver B, Haegermark A, Platten U, et al. Evaluation of psychosocial effects of pre-symptomatic testing for breast/ovarian and colon cancer pre-disposing genes: a 12-month follow-up. Familial Cancer. 2004;3:109–116. doi: 10.1023/B:FAME.0000039863.89137.f9.
    1. Collins VR, Meiser B, Ukoumunne OC, et al. The impact of predictive genetic testing for hereditary nonpolyposis colorectal cancer: three years after testing. Genet Med. 2007;9:290–297. doi: 10.1097/GIM.0b013e31804b45db.
    1. Ertmanski S, Metcalfe K, Trempala J, et al. Identification of patients at high risk of psychological distress after BRCA1 genetic testing. Genet Test Mol Biomarkers. 2009;13:325–330. doi: 10.1089/gtmb.2008.0126.
    1. Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Measure. 1977;1:385–401. doi: 10.1177/014662167700100306.
    1. Beck AT, Epstein N, Brown G, et al. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56:893–897. doi: 10.1037/0022-006X.56.6.893.
    1. Anderson LA, Dedrick RF. Development of the Trust in Physician scale: a measure to assess interpersonal trust in patient-physician relationships. Psychol Rep. 1990;67:1091–1100.
    1. Wolf MS, Chang, C.H., Davis, T., Makoul, G.: Development and validation of the communication and Attudinal self-efficacy scale for cancer (CASE-cancer). Patient Educ Couns 57:333–341, 2005.
    1. Fitzgerald-Butt SM, Bodine A, Fry KM, et al. Measuring genetic knowledge: a brief survey instrument for adolescents and adults. Clin Genet. 2016;89:235–243. doi: 10.1111/cge.12618.
    1. Singer E, Antonucci T, Van Hoewyk J. Racial and ethnic variations in knowledge and attitudes about genetic testing. Genet Test. 2004;8:31–43. doi: 10.1089/109065704323016012.
    1. Rini C, Henderson GE, Evans JP, et al. Genomic knowledge in the context of diagnostic exome sequencing: changes over time, persistent subgroup differences, and associations with psychological sequencing outcomes. Genet Med. 2020;22:60–68. doi: 10.1038/s41436-019-0600-4.
    1. Dunning-Davies J. Finding evidence for black holes. Science. 2004;305:1238. doi: 10.1126/science.305.5688.1238b.
    1. DiMaso SN. Pre-appointment information seeking and scanning behaviors in individuals scheduled for cancer genetics consultations. (Electronic Thesis or Dissertation). Retrieved from .
    1. Graham S, Brookey J. Do patients understand? Perm J. 2008;12:67–69.
    1. Roberts JS, Gornick MC, Le LQ, et al. Next-generation sequencing in precision oncology: patient understanding and expectations. Cancer Med. 2019;8:227–237. doi: 10.1002/cam4.1947.
    1. Giese-Davis J, Collie K, Rancourt KM, et al. Decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer: a secondary analysis. J Clin Oncol. 2011;29:413–420. doi: 10.1200/JCO.2010.28.4455.
    1. Spiegel D, Giese-Davis J. Depression and cancer: mechanisms and disease progression. Biol Psychiatry. 2003;54:269–282. doi: 10.1016/S0006-3223(03)00566-3.
    1. Pilevarzadeh M, Amirshahi M, Afsargharehbagh R, et al. Global prevalence of depression among breast cancer patients: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019;176:519–533. doi: 10.1007/s10549-019-05271-3.
    1. Alexandre J, Brown C, Coeffic D, et al. CA-125 can be part of the tumour evaluation criteria in ovarian cancer trials: experience of the GCIG CALYPSO trial. Br J Cancer. 2012;106:633–637. doi: 10.1038/bjc.2011.593.
    1. Freburger JK, Callahan LF, Currey SS, et al. Use of the Trust in Physician Scale in patients with rheumatic disease: psychometric properties and correlates of trust in the rheumatologist. Arthritis Rheum. 2003;49:51–58. doi: 10.1002/art.10925.
    1. Mainous AG, 3rd, Baker R, Love MM, et al. Continuity of care and trust in one's physician: evidence from primary care in the United States and the United Kingdom. Fam Med. 2001;33:22–27.
    1. Street RL, Jr, Makoul G, Arora NK, et al. How does communication heal? Pathways linking clinician-patient communication to health outcomes. Patient Educ Couns. 2009;74:295–301. doi: 10.1016/j.pec.2008.11.015.
    1. Pellino T, Tluczek A, Collins M, et al. Increasing self-efficacy through empowerment: preoperative education for orthopaedic patients. Orthop Nurs. 1998;17(48–51):54–59.
    1. Anderson RM, Funnell MM, Butler PM, et al. Patient empowerment Results of a randomized controlled trial. Diabetes Care. 1995;18:943–949. doi: 10.2337/diacare.18.7.943.
    1. Roberts JS, Robinson JO, Diamond PM, et al. Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq project. Genet Med. 2018;20:1069–1076. doi: 10.1038/gim.2017.223.
    1. Heshka JT, Palleschi C, Howley H, et al. A systematic review of perceived risks, psychological and behavioral impacts of genetic testing. Genet Med. 2008;10:19–32. doi: 10.1097/GIM.0b013e31815f524f.
    1. Meiser B. Psychological impact of genetic testing for cancer susceptibility: an update of the literature. Psychooncology. 2005;14:1060–1074. doi: 10.1002/pon.933.
    1. Broadstock M, Michie S, Marteau T. Psychological consequences of predictive genetic testing: a systematic review. Eur J Hum Genet. 2000;8:731–738. doi: 10.1038/sj.ejhg.5200532.

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