Pretreatment Body Composition Parameters and HALP Score in Relation to Pathological Complete Response in HER2-Positive Breast Cancer Receiving Neoadjuvant Systemic Therapy

Background/Objectives: Pathological complete response (pCR) is an important early endpoint in HER2-positive breast cancer treated with neoadjuvant therapy. Although tumor biology is a major determinant of response, the potential contribution of host-related factors such as body composition and systemic inflammatory-nutritional status remains uncertain. This study evaluated the associations of pretreatment skeletal muscle index (SMI), myosteatosis, an imaging-defined low-SMI obesity phenotype, and hemoglobin-albumin-lymphocyte-platelet (HALP) score with pCR. Methods: This retrospective single-center study included 114 patients with HER2-positive disease documented on pretreatment biopsy who received neoadjuvant systemic therapy followed by definitive surgery. CT-based body-composition measurements at the L3 level were available in 88 patients. SMI, skeletal muscle radiodensity, myosteatosis, an imaging-defined low-SMI obesity phenotype, and pretreatment HALP score were assessed. Factors associated with pCR were evaluated using Firth penalized logistic regression. Two multivariable models incorporated body-composition variables, HALP, hormone receptor status, simplified clinical T and N categories, HER2-treatment group, age, and Ki-67. Final multivariable analyses included 80 complete cases. Results: pCR was achieved in 59 of 114 patients (51.8%). Hormone receptor-negative tumors had a higher pCR rate than hormone receptor-positive tumors (74.4% vs. 40.0%; p < 0.001). Pretreatment SMI, myosteatosis, the imaging-defined low-SMI obesity phenotype, and HALP were not significantly associated with pCR in univariable analyses. In multivariable analyses, SMI and myosteatosis were not independently associated with pCR, whereas hormone receptor positivity remained associated with lower pCR odds. The treatment-group coefficient indicated lower adjusted pCR odds with trastuzumab alone than with dual HER2 blockade; however, this estimate was based on sparse complete-case subgroup data and should not be interpreted as a comparative treatment-effect estimate. Muscle attenuation and myosteatosis classification differed significantly by CT acquisition type, whereas SMI did not. Conclusions: Pretreatment SMI, myosteatosis, the imaging-defined low-SMI obesity phenotype, and HALP were not significantly associated with pCR in this cohort. Hormone receptor status remained strongly associated with response. Treatment-related estimates and attenuation-based body-composition measures should be interpreted cautiously because of sparse subgroup data, treatment-era confounding, and imaging heterogeneity. Larger prospective studies with standardized imaging are warranted.