Association between genomic recurrence risk and well-being among breast cancer patients

BMC Cancer Association between genomic recurrence risk and well-being among breast cancer patients Valesca P Retl 1 Catharina GM Groothuis-Oudshoorn 0 Neil K Aaronson 1 Noel T Brewer Emiel JT Rutgers Wim H van Harten 0 1 0 Governance and Management, MB-HTSR, University of TwenteSchool , PO Box 217, Enschede, AE 7500 , The Netherlands 1 Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute , Plesmanlaan 121, Amsterdam, CX 1066 , The Netherlands Background: Gene expression profiling (GEP) is increasingly used in the rapidly evolving field of personalized medicine. We sought to evaluate the association between GEP-assessed of breast cancer recurrence risk and patients' well-being. Methods: Participants were Dutch women from 10 hospitals being treated for early stage breast cancer who were enrolled in the MINDACT trial (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). As part of the trial, they received a disease recurrence risk estimate based on a 70-gene signature and on standard clinical criteria as scored via a modified version of Adjuvant! Online. \Women completed a questionnaire 6-8 weeks after surgery and after their decision regarding adjuvant chemotherapy. The questionnaire assessed perceived understanding, knowledge, risk perception, satisfaction, distress, cancer worry and health-related quality of life (HRQoL), 6-8 weeks after surgery and decision regarding adjuvant chemotherapy. Results: Women (n = 347, response rate 62%) reported high satisfaction with and a good understanding of the GEP information they received. Women with low risk estimates from both the standard and genomic tests reported the lowest distress levels. Distress was higher predominately among patients who had received high genomic risk estimates, who did not receive genomic risk estimates, or who received conflicting estimates based on genomic and clinical criteria. Cancer worry was highest for patients with higher risk perceptions and lower satisfaction. Patients with concordant high-risk profiles and those for whom such profiles were not available reported lower quality of life. Conclusion: Patients were generally satisfied with the information they received about recurrence risk based on genomic testing. Some types of genomic test results were associated with greater distress levels, but not with cancer worry or HRQoL. Trial registration: ISRCTN: ISRCTN18543567 Personalized medicine; Genomic profile; 70-gene signature; Patient-centered care; Breast cancer; Chemotherapy - Background Gene expression profiling, an example of personalized medicine, has moved quickly into clinical care. Breast cancer treatment guidelines that incorporate genomic testing include those from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), the 2008 Dutch Clinical Guidelines (CBO) and the 2009 St Gallen guidelines [1]. One gene expression test is the 70-gene signature (Mamma-Print) [2,3] that can accurately distinguish early stage breast tumours at high risk for distant metastasis from low-risk tumours. Several retrospective validation studies have confirmed its prognostic value [4-6], though the effects of receiving results from this test on patient well-being are largely unknown. A randomized controlled trial, the MINDACT (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy; EORTC 10041/BIG 304) evaluated prospectively whether the 70-gene signature selects the right patients for adjuvant chemotherapy better than standard clinicopathological criteria [7,8]. This trial enrolled 6700 early stage breast cancer patients throughout Europe, who had their risk of disease recurrence assessed by both standard clinicopathological criteria and the 70-gene signature. Clinicopathological prognostic risk was assessed through a modified version of Adjuvant! Online [9]. Low risk for distant recurrence was defined as >88% chance of 10-years survival for oestrogen receptor (ER)-positive breast cancer and >92% for ER-negative breast cancer. Concordant genomic high (G-high) and clinicopathological high (C-high) risk patients were recommended to undergo adjuvant chemotherapy, and concordant G-low and C-low risk patients were informed that chemotherapy is not recommended. Discordant patients (C-low/G-high of C-high/G-low) were randomized to treatmentdecision making based on the genomic risk assessment or treatment-decision making based on the clinical risk assessment [10]. Since genomic testing is a recent development, relatively few studies have investigated psychosocial issues surrounding these tests. ONeill et al., in a survey of 139 women who received breast cancer treatment before genomic profiling was available, found a strong interest in genomic testing [11]. Richman et al., in a study of 78 breast cancer patients who had previously received gene expression profiling, reported that many women had an inadequate understanding of gene profiling [12]. In an analysis of data from the same study, Tzeng et al. found that many breast cancer patients preferred a level of shared decision making that was different from what they experienced with their doctors [13]. Lo et al. found that receiving gene expression profiling results lowered patients (n = 89) anxiety [14]. Both Tzeng et al. and Lo et al. found that patients decisions were largely concordant with their gene expression profile results. These studies tended to have small samples, examined the effects of different risk results only minimally, and did not investigate the impact of the combination of gene profiling and clinical risk data in their analyses. Recently, Sulayman et al. reported on the psychosocial and quality of life impact of women receiving an intermediate genomic score [15]. They found that those women who took a passive role in their care reported higher cancer-related distress and cancer worry and lower quality of life than those who took a shared or active role [15]. The primary aims of our study were to evaluate the association between breast cancer patients well-being and the results of a gene expression profile on to compare different recurrence risk groups, according to their genomic and standard clinical risk assessments. We expected higher well-being for the concordant C-low/ G-low risk group (clinical and genomic assessments indicate low risk), lower well-being in patients who did not receive genomic results and lower well being for the discordant C-low/G-high risk groups (clinical parameters indicate low risk while genomic test indicates high risk), especially the group who did not receive chemotherapy. In addition, we examined the extent to which women understood the genomic test information received, risk perception, knowledge, and satisfaction with provided information and with the clinical process. Methods Study sample Women taking part in the MINDACT-trial from 10 hospitals in the Ne (...truncated)