Comment on "Associations of neighborhood deprivation with breast cancer tumor genomics, targeted treatment use, and survival".

INTRODUCTION

Podany et al. examined associations between Area Deprivation Index (ADI) and tumor genomics, PI3K inhibitor use, and survival in 1,127 patients with metastatic breast cancer. While their multi-institutional, genomically annotated dataset is a valuable contribution, several methodological issues warrant scrutiny.

METHODS

We critically reviewed the study's statistical approach, focusing on multiple-comparison handling, potential confounding from ctDNA shedding variability, and the reliability of subgroup survival estimates.

RESULTS

Key findings (TP53, AKT1, overall survival, PI3Ki-use disparity, and Black patient survival disadvantage) relied on borderline p-values from uncorrected multiple comparisons across 19 supplementary tables. Lower visceral, nodal, and soft-tissue metastasis rates in high-deprivation patients suggest reduced ctDNA shedding, which could confound reported mutation-frequency differences, particularly for AKT1. The AKT1 subgroup hazard ratio (6.27) derived from roughly five events, far below recommended events-per-variable thresholds, raising concerns about estimate stability.

CONCLUSION

Addressing multiplicity correction, ctDNA shedding assessment, and transparent event-count reporting would strengthen confidence in the study's conclusions and better inform future prospective research.