Abstract Purpose: Seroma is the most common postoperative complication following mastectomy, often prolonging hospital stays and increasing the need for additional treatment. Despite its high prevalence, the etiology and predictive factors remain unclear. Therefore, identifying reliable predictors and potential causes remains a critical focus in research. This study aimed to identify potential risk factors associated with seroma formation following mastectomy. Methods: We conducted a retrospective analysis of 244 patients who underwent mastectomy at the University Hospital Leipzig between 2019 and 2023. Data was extracted from the patient’s medical record and from pathology reports. The analysis focused on selected factors including epidemiological patient’s characteristics, preoperative treatments (e.g. neoadjuvant chemotherapy), tumor status (e.g. TNM classification), perioperative (e.g. surgery duration) and postoperative variables (e.g. drainage duration). Seroma formation was assessed based on the flow rate from wound drains placed in the breast and axilla and follow-up visits. Statistical methods included Spearman correlation, t-tests, ANOVA, and multivariate regression to identify risk factors associated with seroma development. Results: The median patient age was 51 years (range 18-88). A total number of 301 mastectomies procedures were performed on 244 patients. Of these mastectomies, 215 (71.4%) were conducted due to breast cancer, 24 (8.0%) due to ductal carcinoma in situ and 62 (20.6%) as a prophylactic intervention. In 145 (48.2%) cases a mastectomy with immediate implant-reconstruction was performed, in 156 (51.8%) a mastectomy without reconstruction was performed. In 123 (40.9%) cases the mastectomy was combined with a sentinel node biopsy procedure, in 89 cases (29.6%) with an axillary dissection and in 89 cases (29.6%) no axillary treatment was performed. The median amount of total seroma was 585 ml (range 35-3625 ml). Epidemiological factors found to be significant were patients’ age (r=0.19; p0.001), BMI (r=0.24; p0.0001), hypertension (T=-3.52; p0.001), and diabetes (T=-2.18; p0.05). Among preoperative treatments found to be significant was previous breast surgery (T=2.25; p0.05). Furthermore, significant factors regarding tumor status were, tumor size (r=0.33; p0.001) and histology (F=3.71; p0.001), removed specimen weight (r=0.31; p0.0001), number of metastatic lymph nodes (r=0.42; p0.0001), lymphovascular invasion (r=0.27; p0.0001) and nodal status (r=0.41; p0.0001). Perioperative variables found to be significant were the number of removed lymph nodes regardless of metastastic state (r=0.55; p0.0001), duration of surgery (r=0.13; p0.05) and inserted implant size (r=0.27; p0.001). Significant postoperative parameters were C-reactive protein (CRP) -value on the first postoperative day (r=0.24; p0.0001), amount of seroma in the first 24 hours (r=0.47; p0.0001) and the duration of drainage (r=0.68; p0.0001). Conclusion: These results suggest that both patient-related and treatment-related factors significantly influence postoperative development of seroma following mastectomy. Higher seroma volumes were associated with older age, higher BMI, comorbidities (such as hypertension and diabetes) and lymph node removal. Recognizing these risk factors may help guide postoperative management to reduce complications. Citation Format: L. Weydandt, K. Hein, S. Briest, I. Nel, B. Aktas. What really drives seroma formation? - Insights from a retrospective study of 244 patients undergoing mastectomy abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-23.
Weydandt et al. (Tue,) studied this question.