Abstract Purpose: Mastectomy for large in situ carcinoma is a commonly used therapy. Currently most national and international guidelines recommend sentinel lymph node biopsy because unexpected invasive breast cancer after mastectomy is an indication for sentinel lymph node staging. This cannot be performed after mastectomy and complete axillary dissection would be necessary in these cases. SLN as well as axillary dissection both can cause lifelong complications, especially arm movement impairment. Therefore, the necessity for this additional procedure needs to be addressed. We sought to gain insight into the frequency of unexpected upstaging to invasive breast cancer in case of mastectomy for in situ carcinoma and invasive nodal involvement in a real-world collective. Methods: Data collection was conducted from 2012-2024 in six certified breast cancer centers using a personal interview and data from the patients’ medical records. All patients had histologically confirmed pure DCIS or LCIS prior to mastectomy. All preoperatively diagnosed invasive breast cancer cases were excluded from final analysis. Descriptive statistics and multivariate analyzes were utilized to identify risk factors for upstaging from in situ carcinoma to invasive breast cancer. Results: The study collective included 4307 patients with primary breast cancer or in situ carcinoma. 237 preoperatively diagnosed in situ carcinomas were analyzed. 42/237 (18%) cases were upstaged to invasive breast cancer and positive lymph nodes were found in 8/237 (3%) cases. 71 cases of primary and secondary mastectomy were performed with an upstaging to invasive breast cancer occurring in 19 cases (31%). SLN biopsy in combination with mastectomy was performed in 60 patients and 3 patients with positive lymph nodes were detected. Looking into risk factors for unexpected upstaging on multivariate analyzes only a Ki67 higher then 20% was significantly correlated with an upstaging to invasive carcinoma (p = 0.033). Conclusions: The frequency of unexpected detection of invasive breast cancer in mastectomy for in situ carcinoma, is relatively low, despite comprehensive clinical work up including core needle biopsy. The likelihood of positive nodal involvement is also rather low but remains apparent and has clinical implications for adjuvant therapies. Still, postoperative and long-term complications of SLN biopsy remain an issue. Therefore, omission of SLN biopsy during mastectomy for in situ carcinoma should be discussed individually. Risk factors for upstaging need to be identified and long-term follow up is needed. Novel approaches to a two stage SLN biopsy offer surgical strategies to avoid unnecessary axillary interventions. Citation Format: E. Kuehnle, L. Steinkasserer, C. Mueller, H. Kuehnle, K. Luebbe, K. Noeding, S. Noeding, M. Arfsten, P. Hillemanns, T. Park-Simon. Unexpected invasive breast cancer after mastectomy for in situ carcinoma and implication on axillary management - data from a real-world collective 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 PS2-01-20.
Kuehnle et al. (2026) studied this question.