2659 - Beyond Traditional Borders: Outcomes with Curative Intent Therapy for Stage IV Breast Cancer Defined by Non-Regional Nodal Metastases

E. Braschi Jordan¹, E. D. Brooks², R. Mailhot Vega¹, N. P. Mendenhall¹, C. G. Morris¹, T. Burchianti³, A. M. Deladisma⁴, and J. A. Bradley¹; ¹Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, ²Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, ³University of Florida Health Proton Therapy Institute, Jacksonville, FL, ⁴Department of Surgery, University of Florida College of Medicine Jacksonville, Jacksonville, FL

Purpose/Objective(s): Isolated non-regional lymph node metastases among breast cancer patients are rare and poorly understood events. Optimal treatment paradigms for such patients remain controversial, as the nodal disease distribution is classified as Stage IV but patients may have similar prognosis to those with classic regionally-confined locally advanced breast cancer. Herein, we assess outcomes and toxicities of patients treated with curative intent for M1 breast cancer with non-regional lymphatic spread. Materials/

Methods: In this single institution retrospective review, we evaluated patients with Stage IV breast cancer due to non-regional thoracic and/or cervical lymphatic nodal metastases treated between 2012-2023. All patients underwent curative intent systemic and locoregional therapy consisting of surgery and proton therapy (PT). Toxicity was recorded according to the Common Terminology Criteria for Adverse Effects Version 5.0. Disease-control outcomes were assessed by Kaplan-Meier analysis.
Results: Eleven female patients (median age, 53 years; range, 34-74) were identified, with a median follow-up of 1.6 years (range, 0.1-8.6). Most patients had de-novo (82%) breast cancer, while 18% had recurrent disease. The most common subtype was hormone receptor positive and human epidermal growth factor receptor 2 negative (54%). Involved non-regional nodal basins included combinations of contralateral internal mammary (n=5), contralateral axillary (n=4), mediastinal (n=4), and ipsilateral cervical (n=3) nodes. Ten patients received neoadjuvant chemotherapy. Most underwent mastectomy (73%) with axillary lymph node dissection (64%). Seven patients underwent bilateral chest/breast radiation (RT) and 2 underwent re-RT of the ipsilateral side. Total RT dose ranged from 60-70 Gy in 30-35 fractions, including a boost to undissected involved non-regional nodes in 72% of patients. Two-year overall survival was 74% and distant disease-free survival was 68%. Two patients developed rapid simultaneous in-field nodal and distant disease at 1- and 12-weeks post-RT. Another patient developed widespread distant metastases at 2 months post-RT. Three patients are alive with no evidence of disease >5 years from completion of RT. The only acute grade 3 toxicity was dermatitis in 1 patient. Late grade 2 toxicity occurred in 5 patients, most commonly breast or chest wall fibrosis. Late grade 3+ toxicity was rare.
Conclusion: Comprehensive systemic and locoregional therapy for Stage IV breast cancer confined to thoracic and cervical non-regional lymphatics resulted in rapid progression in one-third of patients and disease control in two-thirds, with a subset achieving a disease-free interval surpassing 5 years. Despite large treatment volumes, acute and late RT toxicity was low with PT. Curative intent therapy should be considered for these patients.