Purpose: In-vivo proton magnetic resonance spectroscopy (MRS) is a non-invasive method of analyzing choline metabolism that has been used to predict breast cancer prognosis. A strong choline peak may be a surrogate for aggressive tumor biology but its clinical relevance is unclear. The present study assessed whether total choline (tCho), as measured by proton MRS, can predict late recurrence in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer. Methods: The study cohort included 261 HR+/HER2- breast cancer patients who underwent diagnostic single-voxel proton MRS (3.0T scanner) prior to first-line surgery from March 2011 to July 2014. The relationships between tCho compound peak integral (tChoi) values and others prognostic factor were analyzed, as were the effects of tChoi on 10-year disease-free survival (DFS) and overall survival (OS). The clinical significance of tChoi was also analyzed using Harrell’s C-index. Results: Mean tChoi in HR+/HER2- study group was 15.47 and we set the cut-off for tChoi at 15 for survival analysis. 10-year DFS differed significantly between tChoi <15 and ≥15 (p = 0.017), with differences differing significantly for late (5–10 years; p = 0.02) but not early (0–5 years; p = 0.323) recurrence. Cox regression analysis showed that tChoi was significantly predictive of 10-year DFS (p = 0.046, OR 2.69) and tended to be predictive of late recurrence (HR 4.36, p = 0.066). Harrell’s C-index showed that the Ki-67 index (AUC = 0.597) and lymphovascular invasion (AUC = 0.545) were also predictive of survival, with the addition of normalized tChoi improving the AUC to 0.622 (p = 0.014), indicating better predictive power. Conclusion: tChoi determined by in vivo MRS was predictive of prognosis in patients with HR+/HER2- early breast cancer. This parameter may serve as a valuable, non-invasive tool to predict prognosis when combined with other known prognostic factors.

Background: The clinical and oncologic significance of residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remains poorly defined. While traditionally regarded as radiologic indicators of residual malignancy warranting complete surgical excision, accumulating evidence suggests that many post-treatment calcifications represent benign or in situ changes with limited prognostic relevance. This systematic review synthesizes current evidence to clarify the diagnostic, pathologic, and oncologic implications of persistent calcifications after NAC. Methods: Following PRISMA 2020 guidelines, we conducted a comprehensive search of PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between January 2000 and May 2025. Eligible studies included adult breast cancer patients treated with NAC who demonstrated residual calcifications on mammography or MRI with corresponding histopathologic or survival data. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle–Ottawa Scale and AMSTAR-2. Results: Twenty-four studies involving over 3000 patients were included. Across cohorts, 35–55% of residual calcifications were benign, and many others corresponded to ductal carcinoma in situ rather than invasive carcinoma. Calcifications frequently persisted despite pathologic complete response (pCR), particularly in HER2-positive and triple-negative subtypes. MRI demonstrated superior concordance with pathology compared with mammography. Persistent calcifications did not consistently correlate with worse disease-free or overall survival when pCR was achieved. Radiologic–pathologic discordance contributed to overtreatment in some cohorts, including unnecessary mastectomy or extensive resections. Conclusions: Residual calcifications after NAC should not be regarded as a definitive surrogate of residual invasive disease nor as an obligatory indication for complete surgical removal. Their frequent benign or in situ pathology and limited prognostic value support a more individualized approach to surgical planning, prioritizing pathologic response and margin status over radiographic calcifications alone.

Background: Chronic widespread pain (CWP) affects approximately 10% of the adult population globally, causing significant physical and psychological distress. Micronutrients, such as iron, copper, zinc, and magnesium, are essential in various physiological functions, and their imbalances may impact pain perception and chronic pain conditions. Methods: This study used Mendelian randomization (MR) to investigate the causal relationships between micronutrient levels and CWP. Data were obtained from genome-wide association studies (GWASs) for iron, copper, zinc, and magnesium, and CWP data were sourced from large-scale GWASs with 461,857 European participants. Genetic variants were used as instrumental variables to infer causal relationships, minimizing confounding factors. Results: MR analysis revealed a significant association between higher iron levels and an increased risk of CWP (IVW, OR 1.01, 95% CI: 1.00–1.01, p = 0.029). This finding was supported by the weighted median and MR-Egger methods. No significant associations were found for copper, zinc, and magnesium levels. Conclusions: These results suggest that iron levels may influence pain perception and chronic pain conditions. Balanced iron levels are crucial for managing chronic pain. Regular monitoring and personalized treatment plans could benefit individuals with CWP. Further research is needed to understand the mechanisms linking micronutrient levels to chronic pain and to develop targeted therapeutic interventions.