RE: Clinician- and facility-level factors associated with chemotherapy dose reductions in stages I-IIIA breast cancer

To the Editor: We read with great interest the article by Sampathkumar et al. examining clinician- and facility-level correlates of chemotherapy dose reductions in stages I-IIIA breast cancer.1 Their use of detailed regimen-level electronic health record data within a large integrated care system is a notable strength. We are concerned, however, that the discussion moves too quickly from association to practice recommendation. The central issue is that lower frequencies of first-cycle dose proportion (FCDP) reduction or average relative dose intensity (ARDI) reduction cannot be assumed to indicate better chemotherapy delivery. The authors appropriately acknowledge that they were unable to determine whether dose modifications were clinically appropriate because laboratory data, toxicity measures, and patient-reported outcomes were unavailable, and early discontinuation was not captured. In our view, this limitation is foundational rather than secondary. If clinically justified dose attenuation cannot be separated from undertreatment, then clinician or facility characteristics associated with less reduction should not be interpreted as markers of more optimal practice. A related concern is the interpretation of ARDI as a prescribing construct. ARDI is better understood as a composite delivery metric because it may reflect several pathways, including dose reduction, treatment delay, and incomplete treatment completion.2-4 This distinction matters for the proposed explanation of lower ARDI in less urban facilities, where the authors invoke access barriers, scheduling constraints, and delayed toxicity management. Such mechanisms may reduce ARDI without necessarily reflecting a different clinician dosing philosophy. Residual confounding may also be more consequential than the discussion suggests. Although the models adjusted for major clinical covariates, key determinants of dose modification were unavailable, including functional status, baseline hematologic and organ reserve, growth-factor support, early toxic effects, transportation burden, and social support. Several clinician- and facility-level variables may therefore act primarily as proxies for patient complexity and supportive-care capacity rather than as independent drivers of dosing decisions. Accordingly, we believe these findings are best viewed as hypothesis-generating. Before recommending subspecialization or practice restructuring to increase volume or practice size, future analyses should distinguish upfront dose reduction, treatment delay, and early discontinuation, and should evaluate toxicity, guideline concordance, and patient outcomes. Without that additional context, less dose reduction should not be presumed to represent better care. AI use disclosure: ChatGPT was used only to assist with language editing, drafting support, sentence refinement, and formatting of this correspondence. ChatGPT was not used for study design, data analysis, data interpretation, reference verification, or generation of original scientific content. The authors reviewed, verified, and approved the final manuscript and take full responsibility for its content. Sheng Yu (Conceptualization, Investigation, Methodology, Writing—original draft, Writing—review & editing), Xiushen Wang (Investigation, Validation, Writing—review & editing), and Hong Ge (Conceptualization, Methodology, Writing—review & editing) No funding was used for this study. The authors have no conflicts of interest to declare. No new data were generated or analyzed for this correspondence.