en Oncology Oncology Original Article Original Article <span style="font-size:14px;"><span style="font-family:Times New Roman;"><span style="line-height:150%"><span new="" roman="" times=""><span style="color:#0033ff;"><em><b><span style="line-height:150%">Background:</span></b></em></span><span style="color:black"><span style="line-height:150%"> Breast cancer is the most common malignancy among women in Iran and worldwide. Although both neoadjuvant and adjuvant chemotherapies are widely used, their impact on relapse-free survival (RFS) and metastasis-free survival (MFS) in real-world settings remains unclear. This study aimed to compare RFS and MFS between neoadjuvant and adjuvant chemotherapy in breast cancer patients. </span></span><br> <em><span style="color:#0033ff;"><span style="line-height:150%"><b>Methods:</b></span></span></em><span style="color:black"><span style="line-height:150%"> A retrospective cohort study was conducted on patients who had received adjuvant or neoadjuvant therapy at Seyed Al-Shohada Hospital between July 2016 and July 2020. The cut-off date was July 202. Kaplan-Meier analysis and Cox regression models were used to evaluate RFS and MFS. To address potential confounding by indication due to non-randomized treatment assignment, inverse probability of treatment weighting (IPTW) was applied using propensity scores based on age, tumor grade, and molecular subtype. </span></span><br> <span style="color:#0033ff;"><span style="line-height:150%"><em><b>Results:</b></em></span></span><span style="color:black"><span style="line-height:150%"> Neoadjuvant therapy was significantly associated with increased relapse risk compared to adjuvant therapy in both multivariate (HR = 3.06, <i>p</i> = 0.030) and IPTW-weighted models (HR = 6.10, p = 0.002). No significant difference in MFS was observed between treatment groups. TNBC was identified as the strongest predictor of metastasis (HR = 6.45, <i>p</i> = 0.001). Subtype-specific analyses revealed better outcomes with adjuvant therapy in Luminal A and improved MFS/RFS with neoadjuvant therapy in TNBC. </span></span><br> <span style="color:#0033ff;"><span style="line-height:150%"><em><b>Conclusion:</b></em></span></span><span style="color:black"><span style="line-height:150%"> Adjuvant therapy was associated with better local disease control (RFS), while MFS was primarily influenced by tumor subtype. These findings highlighted the importance of subtype-tailored therapeutic strategies and supported the use of causal methods such as IPTW in observational oncology research.</span></span></span></span></span></span> Breast cancer, adjuvant treatment, neoadjuvant therapy, metastasis-free survival (MFS), relapse-free survival (RFS) 14 0 http://caspjim.com/browse.php?a_code=A-10-3749-1&slc_lang=en&sid=1 Mina Azarnia Azarnia.mina1667@gmail.com 100319475328460056464 0009-0001-6684-229X No Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mehran Sharifi Sharifi.mehran5056@gmail.com 100319475328460056465 100319475328460056465 Yes Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran Zahra Rezaeian N.rezaii2202@gmail.com 100319475328460056466 100319475328460056466 No Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran Saeedeh Arabzadeh cprc.mui@gmail.com 100319475328460056467 100319475328460056467 No Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran Shaghayegh Haghjooy Javanmard sh_haghjoo@med.mui.ac.ir 100319475328460056468 100319475328460056468 No Applied Physiology Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran