4 (based on lowest level of article analyzed in meta-analysis/systematic review).

High BMI is associated with an increased risk of breast cancer in post-menopausal women but poorer outcomes in all age groups. The underlying mechanism is likely to be multi-factorial. Patients with a high BMI may present later due to body habitus. Some studies have also indicated an increased incidence of biologically adverse features, including a higher frequency of oestrogen receptor (ER negative) tumours, in obese patients. Obese patients have a higher frequency of surgical complications, potentially delaying systemic therapies, and reports suggest that chemotherapy and endocrine therapy are less effective in patients with BMI ≥30 kg/m2.High BMI is generally interpreted as excess adiposity and a World Cancer Research Fund report judged that the associations between BMI and incidence of breast cancer were due to body fatness. However, BMI cannot distinguish lean mass from fat mass, or characterise body fat distribution. Most chemotherapy drugs are dosed according to calculated body surface area (BSA). Patients with a similar BSA or BMI may have wide variations in their distribution of adipose tissue and skeletal muscle (body composition); however, few studies have looked at the effect of this on chemotherapy tolerance or effectiveness. Finally, adjuvant treatments for breast cancer can themselves result in body composition changes.Research is required to fully understand the biological mechanisms by which obesity influences cancer behaviour and the impact of obesity on treatment effectiveness and tolerance so that specific management strategies can be developed to improve the prognosis of this patient group.

IntroductionSystemic anticancer therapy is given to selected patients with early breast cancer (EBC) before or after surgery with the aim of eradicating micrometastatic spread and reducing the risk of cancer recurrence. Chemotherapy treatment is most effective when patients receive the optimum dose, on time and without delays or reductions in their treatment doses. Most chemotherapy drugs are dosed according to body surface area calculated from a patient’s height and weight. These calculations were however designed based on data from normal weight patients. This has resulted in uncertainty as to the optimal dosing for patients with different amounts of blood, muscle and fatty tissue (body composition). This study uses segmental bioelectrical impedance analysis (using the Seca mBCA 515) to determine whether differences in the measures of resistance and reactance, and derived estimates of body composition, are predictive of chemotherapy toxicity in the treatment of EBC.Methods and analysisA prospective observational cohort study of women with EBC in whom adjuvant or neoadjuvant chemotherapy is planned. A total of 300 participants will be recruited across nine UK hospital sites. The primary outcome is to determine if higher fat mass index is associated with increased National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grade 3 (or higher) chemotherapy toxicity.Ethics and disseminationThis study has received ethical approval from the South Central Hampshire B Research Ethics Committee, England (19/SC/0596: IRAS: 263666). The chief investigator and coinvestigators will be responsible for publication of the study findings in a peer-reviewed journal, on behalf of all collaborators.Trial registration numberISRCTN79577461.

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