Dual radiation-induced sarcomas after breast cancer in a TP53 variant carrier

Li–Fraumeni syndrome (LFS) is a hereditary syndrome caused by TP53 variants, conferring a high risk of early-onset malignancies, particularly breast cancer. TP53 variants also increase susceptibility to radiation-induced tumors, complicating therapeutic strategies. This report illustrates a representative case and reviews current recommendations and related challenges. A literature review was conducted on patients with LFS who developed secondary malignancies within previously irradiated fields. We describe a 31-year-old woman with prior breast augmentation and left-sided breast cancer treated with chemotherapy, lumpectomy, axillary dissection, and adjuvant radiotherapy. A TP53 variant was identified post-treatment. 22 months after completing radiotherapy, imaging revealed two suspicious nodules adjacent to the left implant. Despite negative biopsies, mastectomy and implant removal uncovered an undifferentiated pleomorphic sarcoma within the capsule. Subsequently, extensive resection with a latissimus dorsi flap was performed. Histopathological analysis revealed residual chondroblastic osteosarcoma infiltrating muscle tissue. The literature indicates increased radiosensitivity and a higher risk of secondary malignancies in patients with TP53 pathogenic variants. Current guidelines favor mastectomy over breast-conserving surgery and recommend avoiding radiotherapy when feasible. Early genetic testing and multidisciplinary planning are essential to optimize oncologic safety and functional outcomes.