AMAZONE: prevention of persistent pain after breast cancer treatment by online cognitive behavioral therapy—study protocol of a randomized controlled multicenter trial

BACKGROUND: Surviving breast cancer does not necessarily mean complete recovery to a premorbid state of health. Among the multiple psychological and somatic symptoms that reduce the quality of life of breast cancer survivors, persistent pain after breast cancer treatment (PPBCT) with a prevalence of 15–65% is probably the most invalidating. Once chronic, PPBCT is difficult to treat and requires an individualized multidisciplinary approach. In the past decades, several somatic and psychological risk factors for PPBCT have been identified. Studies aiming to prevent PPBCT by reducing perioperative pain intensity have not yet shown a significant reduction of PPBCT prevalence. Only few studies have been performed to modify psychological distress around breast cancer surgery. The AMAZONE study aims to investigate the effect of online cognitive behavioral therapy (e-CBT) on the prevalence of PPBCT. METHODS: The AMAZONE study is a multicenter randomized controlled trial, with an additional control arm. Patients (n=138) scheduled for unilateral breast cancer surgery scoring high for surgical or cancer-related fears, general anxiety or pain catastrophizing are randomized to receive either five sessions of e-CBT or online education consisting of information about surgery and a healthy lifestyle (EDU). The first session is scheduled before surgery. In addition to the online sessions, patients have three online appointments with a psychotherapist. Patients with low anxiety or catastrophizing scores (n=322) receive treatment as usual (TAU, additional control arm). Primary endpoint is PPBCT prevalence 6 months after surgery. Secondary endpoints are PPBCT intensity, the intensity of acute postoperative pain during the first week after surgery, cessation of postoperative opioid use, PPBCT prevalence at 12 months, pain interference, the sensitivity of the nociceptive and non-nociceptive somatosensory system as measured by quantitative sensory testing (QST), the efficiency of endogenous pain modulation assessed by conditioned pain modulation (CPM) and quality of life, anxiety, depression, catastrophizing, and fear of recurrence until 12 months post-surgery. DISCUSSION: With perioperative e-CBT targeting preoperative anxiety and pain catastrophizing, we expect to reduce the prevalence and intensity of PPBCT. By means of QST and CPM, we aim to unravel underlying pathophysiological mechanisms. The online application facilitates accessibility and feasibility in a for breast cancer patients emotionally and physically burdened time period. TRIAL REGISTRATION: NTR NL9132, registered December 16 2020.