Background parenchymal enhancement as a predictor of invasive disease-free survival in hormone receptor-positive, HER2-negative breast cancer.

The study by Cho et al. titled "Background parenchymal enhancement as a predictor of invasive disease-free survival in hormone receptor-positive, HER2-negative breast cancer" has made a valuable contribution to the literature by demonstrating that the degree of background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be an independent prognostic marker for invasive disease-free survival (iDFS) (1). The higher discriminatory power of the combined model including BPE, particularly when compared with the Oncotype DX score, strengthens the potential use of this radiological parameter in clinical decision-making processes. However, we believe it would be useful to discuss some methodological aspects of the study. First, it is well known in the literature that BPE can be influenced by hormonal status (2). Factors such as menstrual cycle phase, breastfeeding/lactation, menopausal status, and use of estrogen replacement therapy have a direct impact on BPE (3). Although menopausal status was included among the patient characteristics in this study, it appears that this variable was not adjusted for in the statistical models. Furthermore, other hormonal determinants were not included in the evaluation. Of course, this situation has some clinical implications. The patients included in the study were those who had received a diagnosis and underwent breast MRI for local staging, meaning that their oncological processes had begun. In this case, scheduled imaging at specific phases of the menstrual cycle may not always be possible due to urgency and clinical priorities. Nevertheless, given the role of hormonal interactions in BPE, a clearer explanation of this limitation or necessary statistical corrections in the study would facilitate its evaluation for readers. However, another noteworthy point is that 88% of the patients had mammographically "dense" breasts. However, the fact that BPE levels were classified as "minimal" or "mild" in 63.4% of the group indicates a different distribution than expected (4,5). This may indicate the subjectivity of BPE assessment and the variability in hormonal status. The lack of separate examination of the relationship or interaction between breast density and BPE makes it difficult to exclude potential confounding effects. The timing of the MRI scans used to assess BPE in the study relative to the treatment process was not clearly stated. In particular, it is unclear when the scans were performed after the biopsy, whether at the time of diagnosis or before or afterneoadjuvant or hormonal therapy. Because it is known that BPE can be affected by hormone levels, inflammatory responses, and chemotherapeutic treatments, this timing information is crucial for standardizing and interpreting imaging findings (6). Furthermore, the status of patients receiving neoadjuvant chemotherapy was not separately classified and analyzed in the study. This carries the risk of overlooking the possibility that BPE levels may have exhibited treatment-related changes. Therefore, the lack of details regarding the timing of the MRI and possible treatment effects constitutes a limiting factor in terms of the internal validity of the model and the clinical interpretation of the findings. Additionally, although almost all patients (99.8%) in the study were reported to have received endocrine therapy, establishing a relationship between BPE and BPE based on the type or response to treatment could strengthenthe study.