2026, Vol. 8, Issue 1, Part A

Introduction: Locally advanced breast cancer (LABC) presents significant therapeutic challenges, often requiring multimodal treatment to achieve locoregional control and surgical resectability. Neoadjuvant endocrine therapy combined with CDK4/6 inhibition and neoadjuvant radiotherapy (NART) has emerged as a potential strategy for tumor downstaging in selected hormone receptor-positive cases.
Case: We report the case of a 61-year-old woman presenting with a long-standing, ulcerated, bleeding right breast mass, associated with weight loss and anemia. Imaging and biopsy confirmed a locally advanced ER+/HER2-low invasive carcinoma, staged cT4bN3M0. Initial management consisted of endocrine therapy with anastrozole and abemaciclib, which achieved marked clinical and radiological tumor regression over 10 months. Given the favorable response and absence of distant metastasis, NART was administered to the right breast and regional lymph nodes. Post-RT imaging demonstrated no vascular invasion, allowing for curative-intent surgery.
An adapted Halsted mastectomy with partial pectoralis excision, axillary dissection, and immediate chest wall reconstruction using a pedicled TRAM flap and V-Y advancement flap was performed. Postoperatively, partial flap necrosis required five additional reconstructive procedures. Final pathology revealed Grade 2 NST carcinoma, ER 100%, PR 5%, HER2-low, pT4bN1M0, with R0 resection. Despite postoperative complications, the patient achieved excellent local control and satisfactory functional and aesthetic results. She remains under regular follow-up, with good upper-limb mobility, no lymphedema, and improved quality of life.
Conclusion: This case demonstrates that combined neoadjuvant endocrine therapy, CDK4/6 inhibition, and NART can successfully downstage selected LABC cases, enabling radical surgical resection with curative intent. NART played a pivotal role in achieving R0 margins and facilitating immediate reconstruction. Further studies are needed to define optimal patient selection and refine multimodal treatment sequencing in LABC.