Do body composition parameters correlate with response to targeted therapy in ER+/HER2- metastatic breast cancer patients? Role of sarcopenia and obesity

Purpose: To investigate the association between body composition parameters, sarcopenia, obesity and prognosis in patients with metastatic ER+/HER2- breast cancer under therapy with cyclin-dependent kinase (CDK) 4/6 inhibitors. Methods: 92 patients with biopsy-proven metastatic ER+/HER2- breast cancer, treated with CDK 4/6 inhibitors between 2018 and 2021 at our center, were included in this retrospective analysis. Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT) and Skeletal Muscle Index (SMI) were measured before starting therapy with CDK 4/6 inhibitors (Palbociclib, Abemaciclib or Ribociclib). Measurements were performed on a computed tomography-derived abdominal image at third lumbar vertebra (L3) level by an automatic dedicated software (Quantib body composition®, Rotterdam, Netherlands). Visceral obesity was defined as a VAT area > 130 cm2. Sarcopenia was defined as SMI < 40 cm2/m2. Changes in breast lesion size were evaluated after 6 months of treatment. Response to therapy was assessed according to RECIST 1.1 criteria. Spearman's correlation and χ2 analyses were performed. Results: Out of 92 patients, 30 were included in the evaluation. Of the 30 patients (mean age 53 ± 12 years), 7 patients were sarcopenic, 16 were obese, while 7 patients were neither sarcopenic nor obese. Statistical analyses showed that good response to therapy was correlated to higher SMI values (p < 0.001), higher VAT values (p = 0.008) and obesity (p = 0.007); poor response to therapy was correlated to sarcopenia (p < 0.001). Moreover, there was a significant association between sarcopenia and menopause (p = 0.021) and between sarcopenia and the persistence of axillary lymphadenopathies after treatment (p = 0.003), while the disappearance of axillary lymphadenopathies was associated with obesity (p = 0.028). Conclusions: There is a growing interest in body composition, especially in the field of breast cancer. Our results showed an interesting correlation between sarcopenia and progression of disease, and demonstrated that VAT can positively influence the response to targeted therapy with CDK 4/6 inhibitors. Larger-scale studies are needed to confirm these preliminary results. Clinical relevance: Sarcopenia and obesity seem to predict negative outcomes in many oncologic