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Context: In India, most breast cancer patients present with advanced stage requiring postmastectomy radiotherapy. Lymphedema is a long-term side effect that causes both physical and psychological distresses.Aims: The present prospective study was carried out to study various factors affecting breast cancer-related lymphedema (BCRL).Subjects and Methods: From January 2015 to March 2016, 100 postmastectomy patients who received adjuvant irradiation to chest wall were selected prospectively. Circumference of both arms was measured before surgery, at start, and at end of radiotherapy followed by 3 monthly intervals till last follow-up. Lymphedema was defined as a difference of ≥2 cm from the baseline in the arm circumference on the side of surgery.Results: At a median follow-up of 24 months, the cumulative incidence of BCRL was 13%. On multivariate analysis, risk of BCRL was significantly associated with higher body mass index (BMI) (P = 0.004), greater number of lymph nodes (LNs) dissected (P = 0.005), higher nodal ratio (P = 0.006), and regional LN radiation (RLNR) (P = 0.048) but not with the type of fractionation (P = 0.094).Conclusions: Adjuvant RLNR, higher BMI, greater number of LNs dissected, and higher nodal ratio significantly increases the risk of development of BCRL. There was no significant difference in the lymphedema with the type of fractionation. Females receiving RLNR should be prospectively monitored for lymphedema to ensure early detection and possible intervention. [ABSTRACT FROM AUTHOR]