NEON-BC: A fiveyear prospective cohort study on the neurological complications of breast cancer: frequency and impact in patientreported outcomes (POCI-01-0145-FEDER-016867)
Instituto de Saúde Pública da Universidade do Porto (ISPUP/UP) • Epidemiology Research Unit Institute of Public Health, University of Porto (EPIUnit) •
The growing number of women surviving for long periods with side effects of breast cancer treatment  highlights the importance of a comprehensive evaluation of the global burden of breast cancer among survivors, using the most common hard
endpoints but also patientreported outcomes (PRO); the latter providing unique information regarding the patients’ health condition, without interpretation by a clinician or anyone else .
Among women with breast cancer, neurological complications, associated with the progression of cancer itself or the exposure to oncological treatments, may be an important cause of impaired functioning in varied domains [3,4]. Although the most
frequently studied are neuropathic pain, chemotherapyinduced peripheral neuropathy and cognitive decline, most previous investigations had relatively short followup periods and did not assess the timing of onset of these conditions or their joint occurrence in the same patients.
Breast cancer survivors were shown to have poorer healthrelated quality of life than the general population , patients submitted to chemotherapy or radiotherapy reported higher levels of sleep disturbances  and the levels of anxiety were higher among those who underwent mastectomy . Younger women were also shown to be more vulnerable to economic distress burden after breast cancer diagnosis . However, little attention has been dedicated to understanding the role of specific neurologic sideeffects of breast cancer or its management as mediators of the impact of cancer in different PRO.
This project was designed to provide new insights on the epidemiology of neurological complications of breast cancer and its treatment, and their impact in PRO, through the accomplishment of two specific objectives: objective 1) to quantify the incidence and prevalence of neurological complications among breast cancer patients, at three and five years after the diagnosis; objective 2) to quantify the association between of the occurrence of the most frequent neurological complications and PRO (quality of life, sleep quality, anxiety and depression), at three and five years after cancer diagnosis.
The proposed investigation will use data from a prospective cohort of breast cancer patients (N=506), assembled in 2012 and already followed one year after the diagnosis . During the first year after the diagnosis, the cumulative incidence of at least one oncologicalrelated neurological complication was 48.4%; the most frequent diagnosed were neuropathic pain (30.8%), chemotherapyinduced peripheral neuropathy (16.8%), phantom breast syndrome/pain (16.6%) and cognitive decline (8.1%).
This proposal comprises the evaluation of the cohort at the third and fifth years after the diagnosis of breast cancer (2015 and 2017, respectively), including systematic and standardized assessment of neurological complications at three and five years, as well as the accurate assessment of trends in cognitive performance, using the Montreal Cognitive Assessment  and Brain on Track ; the latter is a selfadministered webbased cognitive test, performed from home, to be repeated at regular intervals of time that minimizes learning effects by the use of subtests with random elements and alternate sequences. Data on PRO (quality of life, sleep quality and anxiety and depression) will be obtained in both moments of follow-up.
To quantify the frequency of neurological complications of breast cancer up to five years after the diagnosis, we will compute estimates for the cumulative incidence of cognitive decline and prevalence of neuropathic pain and chemotherapyinduced
peripheral neuropathy and the corresponding 95% confidence intervals (95%CI) at three and five years of follow-up. The association between each prevalent neurological complication at three or five years of follow-up, and the variation in the
patients’ quality of life, sleep quality, anxiety and depression between the baseline or 1year assessment and three and five years after the diagnosis, respectively, will be quantified through crude and adjusted regression coefficients, and 95%CI estimates, adjusted for potential confounders, using linear regression. Sample size calculations were based on the best information available in the literature on analyses of the baseline and 1year of follow-up evaluations, and preliminary data of the first 20 women evaluated after three years.
The assembling of the cohort and follow-up of the patients for up to five years was already approved by the Ethics Committee of the hospital involved.
The expected results of this investigation may contribute to a more accurate characterization of the burden associated with breast cancer and breast cancer treatment in the patients’ wellbeing, as well as to help to develop strategies to minimize the impact of these conditions among breast cancer survivors.