Innovations in patient-centered breast cancer research

Abstract

Although breast cancer prognosis has improved in the past decades, treatment still severely impacts patients’ quality of life (QoL), emotional and sexual functioning. Many experimental interventions rapidly arise aiming to improve breast cancer care. Randomized controlled trials (RCTs) are required to identify which of these interventions are (most) effective, with the least side effects and best QoL. To evaluate side effects and QoL, patient-reported outcomes (PROs) are needed. RCTs are the gold standard to show effectiveness of treatments, but are often beset by recruitment issues, disappointment bias and limited generalizability. PROs are gaining popularity, but the questionnaires used to collect PROs are often long. Therefore, novel ways to conduct efficient randomized studies are needed, and novel ways to efficiently collect PROs are needed as well. The focus of this thesis was to explore and evaluate potential solutions for these challenges. The main focus of part 1 of this thesis (Chapter 2 – 5) was implementation and evaluation of the novel cmRCT design in a clinical breast cancer setting. In Chapter 2 ethical pros and cons of cmRCT were evaluated with reference to ethical guidelines (e.g. Declaration of Helsinki). A staged-informed consent procedure was proposed to avoid the identified ethical challenges. Chapter 3 described the implementation of the UMBRELLA cohort – the first cmRCT cohort in a clinical breast cancer setting. Chapter 4 presented survey results evaluating patients’ understanding of the cmRCT design. This study was conducted among participants of the three ongoing cmRCT cohorts with embedded trials in our hospital in the field of breast cancer, bone metastases and colorectal cancer. Chapter 5 showed results from an observational study conducted within UMBRELLA with routine care data and PROs. This study aimed to assess prevalence, and determinants of breast edema in patients treated with breast-conserving therapy, and its effect on QoL. In part 2 (Chapter 6 – 8), the aim was to evaluate novel methods to improve PRO utilization. Chapter 6 explored potential advantages of using a supportive breast cancer app in clinical practice, including its potential to collect PROs. In Chapter 7, results were presented from the first RCT (i.e. BRIOS trial) where the PRO-instrument ‘BREAST-Q’ was used as the primary outcome. The BRIOS trial was a pragmatic RCT comparing cosmetic satisfaction and HR-QoL after a novel one-stage implant-based breast reconstruction technique using an acellular dermal matrix (ADM), and the standard of care two-stage procedure (i.e. tissue expanders followed by definitive breast implant). Chapter 8 described the development and evaluation of the short and individualized version of the BREAST-Q by applying computerized adaptive testing (CAT). Chapter 9 provided an overall summary, and Chapter 10 concluded with a general discussion and future perspectives on patient-centered breast cancer research. This thesis concluded by stating that the cohort multiple randomized controlled trial (cmRCT) design is a logistically and ethically feasibly study design. Also, PROs may be used as primary endpoints in RCTs, health apps are promising to collect PROs, and computerized adaptive testing successfully shortened the BREAST-Q with acceptable loss of measurement precision.