Meta-analysis finds BMI affects pCR rates in breast cancer patients receiving neoadjuvant chemotherapy

This systematic review and meta-analysis examined the relationship between body mass index (BMI) and treatment response in patients with breast cancer undergoing neoadjuvant chemotherapy. The analysis pooled data from 15,235 patients across multiple studies, though the specific clinical settings and geographic locations were not reported. The population consisted exclusively of breast cancer patients receiving neoadjuvant chemotherapy, with BMI categorized for comparison. The study design represents a comprehensive synthesis of existing observational evidence on this clinical question.

The intervention was neoadjuvant chemotherapy, though specific regimens, dosing protocols, and treatment durations were not detailed in the meta-analysis. The comparator was BMI categories, analyzed in three distinct comparisons: overweight/obese versus normal/low BMI, underweight versus normal BMI, and overweight/obese versus normal BMI. This categorization approach allowed for examination of BMI effects across the weight spectrum in relation to chemotherapy response.

The primary outcome was pathological complete response (pCR) rate. The analysis found that overweight or obese patients had a significantly reduced pCR rate compared to patients with normal or low BMI, with an odds ratio of 0.79 (p = 0.040). When comparing overweight and obese cohorts specifically to those with normal BMI, the pCR rate was lower with an odds ratio of 0.83 (p < 0.0001). Conversely, the underweight cohort demonstrated a higher pCR rate compared to those with normal BMI, with an odds ratio of 1.56 (p = 0.015). Absolute numbers for pCR rates were not reported, limiting interpretation of clinical magnitude.

No specific secondary outcomes were reported in this meta-analysis. The focus remained exclusively on pCR as the treatment response endpoint. The absence of secondary outcomes such as event-free survival, overall survival, or specific pathological response measures beyond pCR represents a limitation in understanding the broader clinical implications of BMI on neoadjuvant chemotherapy outcomes.

Safety and tolerability findings were not reported in this meta-analysis. The analysis did not include data on adverse event rates, serious adverse events, treatment discontinuations, or specific toxicities related to neoadjuvant chemotherapy across BMI categories. This represents a significant gap in understanding whether BMI influences not only treatment efficacy but also treatment tolerability and safety profiles.

These results contribute to a growing body of literature examining the obesity paradox in oncology, where excess weight has been associated with both positive and negative outcomes depending on cancer type and treatment context. Prior studies in breast cancer have yielded mixed results regarding BMI and chemotherapy response, with some showing reduced efficacy in obese patients potentially due to pharmacokinetic factors, while others have shown no significant association. This meta-analysis provides quantitative synthesis suggesting a consistent direction of effect across multiple studies.

Key methodological limitations include the observational nature of the included studies, which prevents establishment of causality. The authors specifically note that standardized BMI definitions are needed across studies to improve comparability. Additionally, the analysis could not account for potential confounding factors such as differences in chemotherapy regimens, dosing strategies (including dose capping), tumor biology subtypes, or patient comorbidities that might influence both BMI and treatment response. The absence of absolute pCR rates limits assessment of clinical significance beyond statistical significance.

Clinical implications suggest that BMI may be a factor to consider when evaluating expected response to neoadjuvant chemotherapy in breast cancer patients. However, given the observational nature of the evidence, these findings should not lead to treatment modifications based solely on BMI. Clinicians should recognize that overweight and obese patients in this analysis showed reduced pCR rates, while underweight patients showed increased pCR rates, but these associations require confirmation in prospective studies before influencing clinical decision-making.

Unanswered questions include whether BMI-associated differences in pCR translate to differences in long-term outcomes such as recurrence-free or overall survival. The mechanisms underlying these associations remain unclear—whether they relate to pharmacokinetic factors, tumor biology differences across BMI categories, or other confounding variables. Future well-designed prospective studies are needed to validate these observations and determine whether weight management interventions could potentially modify chemotherapy response in breast cancer patients.