We read with great interest the multicenter, prospective, randomized controlled trial by Li and colleagues evaluating the oncologic safety and clinical effectiveness of immediate autologous fat grafting (IAFG) at the time of breast-conserving surgery (BCS) for breast cancer1. The study addresses an important clinical question, and the authors are to be commended for conducting a randomized trial in a field otherwise dominated by retrospective data. Nevertheless, several methodological and interpretive considerations merit discussion, as they influence the strength and scope of the conclusions regarding oncologic safety and clinical effectiveness. The principal limitation concerns generalizability. Although ER and HER2 status were reported in the baseline characteristics table, the trial excluded patients receiving neoadjuvant chemotherapy (NACT). In contemporary practice, NACT represents the standard of care for triple-negative and HER2-positive breast cancer, except in cases of very small, node-negative tumors. The exclusion of patients treated with NACT therefore likely enriched the cohort for biologically favorable, predominantly luminal tumor patients undergoing upfront surgery. It is precisely in higher-risk biological subtypes – particularly TNBC and HER2-positive disease treated with systemic therapy – where theoretical concerns regarding adipose-derived stromal and stem cell interactions within the tumor microenvironment remain most clinically relevant and uncertain2. The reported locoregional recurrence rates (0.6% in the IAFG arm vs 2.4% in controls at a median follow-up period of 62.8 months) are notably low, indicating that the study operated in a low-event context. Sparse event counts limit statistical power to detect modest but clinically meaningful differences. A non-significant P-value should not be interpreted as evidence of equivalence, as the absence of evidence does not constitute evidence of absence. Reporting absolute risk differences and hazard ratios with corresponding confidence intervals would allow readers to better appraise the precision and potential upper bounds of the safety estimate. The findings are, therefore, most appropriately interpreted as applicable to patients with early-stage biologically favorable disease not requiring NACT, rather than extrapolated to TNBC, HER2-positive, or neoadjuvant-treated populations. A second methodological consideration relates to recurrence estimation. Although the cumulative incidence of recurrence is described, Kaplan–Meier and Cox regression methods were applied. In the presence of competing events like death or second primary malignancies, Kaplan–Meier estimates may overstate event probability3. Clarification as to whether competing-risk cumulative incidence methods (e.g., Fine–Grey modeling) were considered would strengthen confidence in the recurrence analysis. AN explicit confirmation that the analyses were conducted on a strict intention-to-treat basis, with full CONSORT-compliant accounting of post-randomization exclusions, would also enhance transparency. With respect to surgical outcomes, the manuscript does not report the incidence of fat necrosis or radiologic sequelae related to IAFG during surveillance. Fat necrosis and oil cyst formation are recognized consequences of lipofilling and may lead to additional imaging, biopsy, or patient anxiety. A recent systematic review and meta-analysis by Lucocq and colleagues reported that immediate lipofilling is associated with measurable rates of fat necrosis, although without demonstrable adverse oncologic impact4. The inclusion of fat necrosis rates and radiologic re-intervention data would provide a more comprehensive assessment of clinical effectiveness and safety. Regarding patient-reported outcomes, the improvements in BREAST-Q domains are encouraging. The authors appropriately acknowledge the limitation that preoperative BREAST-Q baseline measurements were not obtained. Without baseline scores, it is not possible to determine the magnitude of within-patient change or exclude potential baseline imbalances. Furthermore, esthetic evaluation appears to rely exclusively on patient-reported outcomes without independent, blinded photographic panel assessment, as recommended in breast-conserving therapy research standards5. In an unblinded surgical trial, the absence of assessor-blinded objective scoring introduces susceptibility to perception bias, particularly in subjective domains such as satisfaction with breast appearance and psychosocial well-being. In summary, this randomized trial provides valuable prospective evidence supporting the feasibility of IAFG during BCS in a carefully selected, low-risk population undergoing upfront surgery. However, the low recurrence event rate, exclusion of neoadjuvant-treated and higher-risk biological subtypes, and absence of reported fat necrosis and blinded esthetic assessment suggest that the findings are best interpreted as demonstrating no detectable safety signal within a favorable-biology cohort during the observed follow-up, rather than definitive oncologic equivalence across breast cancer subtypes. Further adequately powered studies in TNBC, HER2-positive, and neoadjuvant-treated populations are required to address this remaining uncertainty. Ethical approval Not applicable. Consent Not applicable. Author contributions J.V.: Writing draft , editing and final proof reading; K.M.: Conceptualization, editing, proof reading.
Venkataraman et al. (Thu,) studied this question.