A retrospective study exploring clinical, biological and behavioural factors contributing to changes in body weight following early breast cancer diagnosis.

Abstract

Background: Changes in body weight and adiposity levels can follow breast cancer (BC) diagnosis and treatment, which could result in poor long-term BC outcomes. The factors associated with these changes and the biological mechanisms underlying them remain unclear. Aims, methods, sample and data analysis: A longitudinal retrospective study was conducted to explore weight change post- diagnosis and its association with BC treatment, disease characteristics and biological and behavioural factors. A second aim was to examine factors associated with adiposity and metabolic parameters measured at the end of the follow up. 239 women diagnosed with BC one to seven years prior to study entry attending a specialist BC centre were recruited. Weight from BC diagnosis to the study entry, BC treatments received, disease characteristics, menopausal status, smoking status and age were collected from medical notes. Genetic profile (FTO, Mc4R), body fat and fat free mass, waist circumference and fasting glucose and insulin levels were measured once, at study entry only. Associations were examined using t-tests, correlations, regression and multilevel modelling. Results: Participants were followed for a mean of 47.46 months (SD: 20.45). Average weight change across the sample from diagnosis to 12, 24, 36 and 48 months post-diagnosis was + 1.30 kg, + 0.85 kg, + 1.59 kg and + 0.42 kg respectively (increased mean weight). At 12 months, 61% gained weight, 32% lost weight and 7% remained the same. Nearly all participants had weight changes at 24, 36 and 48 months post-diagnosis. Based on evidence, large weight changes (over 10% of weight at diagnosis) were considered clinically relevant. At 24 months post- diagnosis, 6% of participants had an important decrease of weight, 8% had an important weight gain and 86% of participants had no potentially relevant weight change (less than 10% weight change). Notably, 62.9% of the sample was overweight or obese (BMI larger than 25 kg/m2) at the time of diagnosis. Chemotherapy was not associated with statistically significant weight change post- diagnosis. Tamoxifen contributed significantly to weight change at 24 and 36 months, whereas smoking status and weight at diagnosis were significant predictors of weight change in the first 12 months of diagnosis. Time-invariant multilevel models fitted showed differences in rate of weight change across women. The differences were predicted by tamoxifen used. Moreover, time-varying models indicated that weight post-diagnosis was larger among tamoxifen users compared to non-users (estimated magnitude of the difference 1.09 kg, 95% CI: -1.63 to -0.56, p<0.01) and among anastrozole users (difference 0.85 kg, 95% CI: -1.48 to -0.21, p<0.01). Body adiposity parameters were significantly associated with larger body weight and older age at the time of diagnosis (both p<0.01), whereas glucose and insulin levels were predicted by higher weight at diagnosis (p=0.05 and p<0.01) and the presence of the risky A-allele of the FTO gene (p=0.03 and p=0.01 respectively). Conclusions: Findings confirmed that on average weight increased post BC diagnosis. The magnitude of the changes in body weight and the levels of body fat and waist circumference found among participants could compromise their BC prognosis and increase risk of obesity-related diseases, such as type-two diabetes. Understanding the factors associated with weight changes or adiposity and metabolic levels can help health professionals to identify patients at risk. The study has found that hormone therapy contributed to differences in weight and rate of weight change post-diagnosis and that weight at the time of BC diagnosis was a predictor of body adiposity and metabolic parameters at the end of the follow up. Nonetheless the effects of other variables (i.e. smoking status, genetic profile and other variables not included in this study) cannot be ruled out. Because of the potential negative effects that large body weight at diagnosis, weight changes post diagnosis, excessive adiposity and high insulin levels have, it is imperative to assess those parameters following BC diagnosis and to implement care plans to control them and help newly diagnosed BC patients to achieve optimal weight, body adiposity parameters and a healthy metabolic status.