Validation of the Return-to-Work Obstacles and Self-Efficacy Scale for Women on Sick Leave Due to Breast Cancer (ROSES-BC).

PURPOSE: Breast cancer (BC) is the most frequently diagnosed cancer among women. Approximately 40% of BC survivors are diagnosed during the peak years of their professional career. Women face numerous obstacles when returning to work (RTW) after BC. Their decision-making process and self-efficacy to overcome these barriers may undergo alterations. The objective of this study was to validate the Return-to-work Obstacles and Self-Efficacy Scale (ROSES) for BC survivors, with a focus on three psychometric properties: construct validity, test-retest reliability, and predictive validity. METHODS: This prospective study consists of three phases: Phase 1 (baseline, during sick leave) was conducted to evaluate construct validity, Phase 2 (2 weeks later) assessed test-retest reliability, and Phase 3 (6-month follow-up, RTW or not) aimed to evaluate predictive validity. A total of 153 BC survivors participated in Phase 1 of the study, where they completed the 10 dimensions of the ROSES (e.g., fear of relapse, cognitive difficulties). Confirmatory factor analyses (CFA), Pearson correlations, and Cox regressions were performed, with respect to each phase. RESULTS: The mean duration for RTW with the same employer was 62.7 weeks. CFAs confirmed the ROSES structure, which had previously been established for other health conditions, showing satisfactory coefficients. Significant Pearson correlation coefficients were observed between the ROSES dimensions from Phase 1 to Phase 2, ranging from 0.66 to 0.88. When considering various confounding variables, chemotherapy treatment and cognitive difficulties (ROSES dimension) emerged as the only significant predictors of RTW. CONCLUSION: These findings support the utilization of the ROSES in clinical and research settings for BC survivors to improve their successful RTW. After an initial screening using the ROSES, occupational health professionals can further conduct a focused and thorough evaluation of specific dimensions, such as cognitive difficulties. Additional research and information are required to assist BC survivors in dealing with cognitive impairments induced by chemotherapy when they return to work.

Building resilience in oncology teams: Protocol for a realist evaluation of multiple cases.

BACKGROUND: Teams caring for people living with cancer face many difficult clinical situations that are compounded by the pandemic and can have serious consequences on professional and personal life. This study aims to better understand how a multi-component intervention builds resilience in oncology teams. The intervention is based on a salutogenic approach, theories and empirical research on team resilience at work. This intervention research involves partnership between researchers and stakeholders in defining situations of adversity and solutions appropriate to context. METHODS: The principles of realist evaluation are used to develop context-mechanism-outcome configurations of a multi-component intervention developed by researchers and field partners concerned with the resilience of oncology teams. The multiple case study involves oncology teams in natural contexts in four healthcare establishments in Québec (Canada). Qualitative and quantitative methods are employed. Qualitative data from individual interviews, group interviews and observation are analyzed using thematic content analysis. Quantitative data are collected through validated questionnaires measuring team resilience at work and its effect on teaming processes and cost-effectiveness. Integration of these data enables the elucidation of associations between intervention, context, mechanism and outcome. DISCUSSION: The study will provide original data on contextual factors and mechanisms that promote team resilience in oncology settings. It suggests courses of action to better manage difficult situations that arise in a specialized care sector, minimize their negative effects and learn from them, during and after the waves of the pandemic. The mechanisms for problem resolution and arriving at realistic solutions to professional workforce and team effectiveness challenges can help improve practices in other settings.

Risk-Stratified Pathways for Cancer Survivorship Care: Insights from a Deliberative Multi-Stakeholder Consultation.

Risk-stratified pathways of survivorship care seek to optimize coordination between cancer specialists and primary care physicians based on the whole person needs of the individual. While the principle is supported by leading cancer institutions, translating knowledge to practice confronts a lack of clarity about the meaning of risk stratification, uncertainties around the expectations the model holds for different actors, and health system structures that impede communication and coordination across the care continuum. These barriers must be better understood and addressed to pave the way for future implementation. Recognizing that an innovation is more likely to be adopted when user experience is incorporated into the planning process, a deliberative consultation was held as a preliminary step to developing a pilot project of risk-stratified pathways for patients transitioning from specialized oncology teams to primary care providers. This article presents findings from the deliberative consultation that sought to understand the perspectives of cancer specialists, primary care physicians, oncology nurses, allied professionals, cancer survivors and researchers regarding the following questions: what does a risk stratified model of cancer survivorship care mean to care providers and users? What are the prerequisites for translating risk stratification into practice? What challenges are involved in establishing these prerequisites? The multi-stakeholder consultation provides empirical data to guide actions that support the development of risk-stratified pathways to coordinate survivorship care.

Collaborative governance in the Quebec Cancer Network: a realist evaluation of emerging mechanisms of institutionalization, multi-level governance, and value creation using a longitudinal multiple case study design.

BACKGROUND: People living with and beyond cancer (PLC) receive various forms of specialty care at different locations and many interventions concurrently or over time. They are affected by the operation of professional and organizational silos. This results in undue delays in access, unmet needs, sub-optimal care experiences and clinical outcomes, and human and financial costs for PLCs and healthcare systems. National cancer control programs advocate organizing in a network to coordinate actions, solve fragmentation problems, and thus improve clinical outcomes and care experiences for every dollar invested. The variable outcomes of such networks and factors explaining them have been documented. Governance is the "missing link" for understanding outcomes. Governance refers to the coordination of collective action by a body in a position of authority in pursuit of a common goal. The Quebec Cancer Network (QCN) offers the opportunity to study in a natural environment how, why, by whom, for whom, and under what conditions collaborative governance contributes to practices that produce value-added outcomes for PLCs, healthcare providers, and the healthcare system. METHODS/DESIGN: The study design consists of a longitudinal case study, with multiple nested cases (4 local networks nested in the QCN), mobilizing qualitative and quantitative data and mixed data from various sources and collected using different methods, using the realist evaluation approach. Qualitative data will be used for a thematic analysis of collaborative governance. Quantitative data from validated questionnaires will be analyzed to measure relational coordination and teamwork, care experience, clinical outcomes, and health-related health-related quality of life, as well as a cost analysis of service utilization. Associations between context, governance mechanisms, and outcomes will be sought. Robust data will be produced to support decision-makers to guide network governance towards optimized clinical outcomes and the reduction of the economic toxicity of cancer for PLCs and health systems.

Risk of adverse events with the addition of targeted agents to endocrine therapy in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis.

BACKGROUND: Combining targeted agents and endocrine therapy (ET) improves outcomes in hormone receptor-positive metastatic breast cancer patients but increases the risk of adverse events (AEs). This meta-analysis aims to estimate the comparative risk of AEs with ET in addition to targeted agents in this setting. METHODS: A systematic literature search of MEDLINE, EMBASE, Cochrane Library and conference proceedings up to July 17th 2017 was conducted to identify randomized controlled trials investigating ET with or without CDK4/6, mTOR, PI3K inhibitors and anti-HER2 agents. We calculated summary risk estimates (odds ratio, OR) and 95% confidence intervals (CI) for each AE within each class of targeted agents for each trial, and pooled analysis using the random and fixed effect models. RESULTS: Sixteen studies (n=8529 patients) were included. The addition of targeted agents to ET was associated with a significant higher risk of grade 3-4 AEs: OR 2.86 (95% CI 2.49-3.27) for CDK4/6 inhibitors, 1.88 (95% CI 1.39-2.53) for mTOR inhibitors, 2.05 (95% CI 1.63-2.58) for PI3K inhibitors, and 2.48 (95% CI 1.09-5.66) for anti-HER2 agents. The highest class-specific risks were neutropenia grade 3-4 for CDK4/6 inhibitors (OR 40.77; 95% CI 19.52-85.19), stomatitis grade 3-4 for mTOR inhibitors (OR 11.92; 95% CI 3.68-38.57), hyperglycemia grade 3-4 for PI3K inhibitors (OR 40.93; 95% CI 10.08-166.22) and diarrhea for anti-HER2 agents (OR 9.93; 95% CI 4.71-20.95). CONCLUSIONS: Adding targeted agents to ET is associated with a significant increased risk of AEs. The risk of developing different AEs varies largely according to the type of agent used.

Optimizing clinical and organizational practice in cancer survivor transitions between specialized oncology and primary care teams: a realist evaluation of multiple case studies.

BACKGROUND: Cancer is now viewed as a chronic disease, presenting challenges to follow-up and survivorship care. Models to shift from haphazard, suboptimal and fragmented episodes of care to an integrated cancer care continuum must be developed, tested and implemented. Numerous studies demonstrate improved care when follow-up is assured by both oncology and primary care providers rather than either group alone. However, there is little data on the roles assumed by specialized oncology teams and primary care providers and the extent to which they work together. This study aims to develop, pilot test and measure outcomes of an innovative risk-based coordinated cancer care model for patients transitioning from specialized oncology teams to primary care providers. METHODS/DESIGN: This multiple case study using a sequential mixed-methods design rests on a theory-driven realist evaluation approach to understand how transitions might be improved. The cases are two health regions in Quebec, Canada, defined by their geographic territory. Each case includes a Cancer Centre and three Family Medicine Groups selected based on differences in their determining characteristics. Qualitative data will be collected from document review (scientific journal, grey literature, local documentation), semi-directed interviews with key informants, and observation of care coordination practices. Qualitative data will be supplemented with a survey to measure the outcome of the coordinated model among providers (scope of practice, collaboration, relational coordination, leadership) and patients diagnosed with breast, colorectal or prostate cancer (access to care, patient-centredness, communication, self-care, survivorship profile, quality of life). Results from descriptive and regression analyses will be triangulated with thematic analysis of qualitative data. Qualitative, quantitative, and mixed methods data will be interpreted within and across cases in order to identify context-mechanism associations that explain outcomes. DISCUSSION: The study will provide empirical data on a risk-based coordinated model of cancer care to guide actions at different levels in the health system. This in-depth multiple case study using a realist approach considers both the need for context-specific intervention research and the imperative to address research gaps regarding coordinated models of cancer care.

Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer.

In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting MET inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor of MET, RON, AXL, TIE-2, and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Patients with centrally reviewed primary TNBC and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single-arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. In stage 2, correlative studies of MET, PTEN, EGFR, and p53 on archival and fresh tumor specimens were performed along with enumeration of CTCs. 45 patients were enrolled with 37 patients having response evaluable and centrally confirmed primary TNBC (cTNBC). There were 2 partial responses (ITT 4.7 % response evaluable cTNBC 5.4 %) with a median duration of 4.4 months (range 3.7-5 m) and 15 patients had stable disease (ITT 33 %, response evaluable cTNBC 40.5 %) with a median duration of 5.4 months (range 2.3-9.7 m). The most common toxicities (all grades/grade 3) were nausea (64/4 %), fatigue (60/4 %), hypertension (58/49 %), and diarrhea (40/7 %). Six serious adverse events were considered possibly related to foretinib and 4 patients went off study due to adverse events. There was no correlation between MET positivity and response nor between response and PTEN, EGFR, p53, or MET expression in CTCs. Although CCTG IND 197 did not meet its primary endpoint, the observation of a clinical benefit rate of 46 % in this cTNBC population suggests that foretinib may have clinical activity as a single, non-cytotoxic agent in TNBC (ClinicalTrials.gov number, NCT01147484).

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

BACKGROUND AND OBJECTIVES: Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. METHODS: An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). RESULTS: The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. CONCLUSIONS: From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study.

BACKGROUND: This phase II study evaluated the efficacy and safety/tolerability of sunitinib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC). METHODS: Eligible patients received sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3-weekly (loading, 8 mg/kg; then 3-weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. The primary endpoint was objective response rate (ORR). RESULTS: Sixty patients were enrolled and evaluable for safety; 57 were evaluable for efficacy. The majority of patients (58%) had received no prior chemotherapy in the metastatic setting. The ORR was 37%; the clinical benefit rate (CBR; percent objective response plus stable disease ≥ 24 weeks) was 56%. Among patients who were treatment-naïve or had received only adjuvant therapy, the ORR was 44% and the CBR was 59%. Overall, median overall survival had not been reached and the 1-year survival rate was 91%. The majority of adverse events (AEs) were mild to moderate in severity. Forty percent of patients experienced AEs related to measured left ventricular ejection fraction (LVEF) declines, which occurred more frequently in patients who had received prior anthracycline treatment. Ten percent of patients exhibited symptoms related to LVEF declines. One patient died on study from cardiogenic shock. Antitumor response and several safety parameters appeared to correlate with sunitinib exposure. CONCLUSIONS: Sunitinib plus trastuzumab demonstrated antitumor activity in patients with HER2-positive ABC, particularly those who were treatment-naïve or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with HER2-positive ABC who had not received prior anthracycline therapy. TRIAL REGISTRATION: NCT00243503.

Adjuvant docetaxel for node-positive breast cancer.

BACKGROUND: We compared docetaxel plus doxorubicin and cyclophosphamide (TAC) with fluorouracil plus doxorubicin and cyclophosphamide (FAC) as adjuvant chemotherapy for operable node-positive breast cancer. METHODS: We randomly assigned 1491 women with axillary node-positive breast cancer to six cycles of treatment with either TAC or FAC as adjuvant chemotherapy after surgery. The primary end point was disease-free survival. RESULTS: At a median follow-up of 55 months, the estimated rates of disease-free survival at five years were 75 percent among the 745 patients randomly assigned to receive TAC and 68 percent among the 746 randomly assigned to receive FAC, representing a 28 percent reduction in the risk of relapse (P=0.001) in the TAC group. The estimated rates of overall survival at five years were 87 percent and 81 percent, respectively. Treatment with TAC resulted in a 30 percent reduction in the risk of death (P=0.008). The incidence of grade 3 or 4 neutropenia was 65.5 percent in the TAC group and 49.3 percent in the FAC group (P<0.001); rates of febrile neutropenia were 24.7 percent and 2.5 percent, respectively (P<0.001). Grade 3 or 4 infections occurred in 3.9 percent of the patients who received TAC and 2.2 percent of those who received FAC (P=0.05); no deaths occurred as a result of infection. Two patients in each group died during treatment. Congestive heart failure and acute myeloid leukemia occurred in less than 2 percent of the patients in each group. Quality-of-life scores decreased during chemotherapy but returned to baseline levels after treatment. CONCLUSIONS: Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.