Navigating Oligometastasis and Oligoprogression in Stage IV Breast Cancer

The management of stage IV breast cancer is evolving beyond a binary view of localized vs widespread disease. During the 43rd Annual Miami Breast Cancer Conference, Eileen Connolly, MD, PhD, highlighted the growing importance of identifying "oligo-states"—specifically oligometastatic and oligoprogressive disease—where patients experience progression in a limited number of sites, typically 5 or fewer.

As systemic therapies continue to improve, the integration of metastasis-directed therapy (MDT), such as stereotactic ablative body radiotherapy (SABR), is becoming a strategic tool to prolong disease control. By targeting specific lesions, clinicians may be able to maintain current systemic lines and delay the transition to more aggressive treatments.

Connolly is an assistant professor in radiation oncology, director of Clinical Research, and co-lead of the Breast Cancer Disease-Based Team at Columbia University Herbert Irving Comprehensive Cancer Center.

Beyond Binary: Defining Oligo-States

• Oligometastatic: A distinct intermediate clinical entity between localized and widespread disease. Typically defined as 5 or fewer lesions.²
• Oligoprogressive: Progression in limited sites (~1-5) after an initial response to systemic therapy.
• The Goal: Utilizing metastasis-directed therapy (MDT) to prolong disease control and maintain current systemic lines.

Breast Cancer Radiosensitivity

• In a cohort of lung metastases, the radiosensitivity index was the lowest compared with other histologies.³
• The trial did not find a need for significant dose deescalation.

Clinical Indications for MDT in Stage IV Breast Cancer

• High-Risk Metastases: Areas threatening immediate morbidity (e.g., spinal cord compression or weight-bearing bone).
• Phase 2 randomized controlled trial may decrease risk of severe related events, including cord compression, path fracture, surgery, or radiation.⁴

AVATAR Trial

• The phase 2 TROG 20.03 AVATAR trial (ACTRN12620001212943) assessed stereotactic ablative body radiotherapy for oligoprogressive estrogen receptor–positive breast cancer.⁵ The primary end of event-free survival was met with 47% (95% CI, 29%-63%) of patients being event-free at 6 months or more.
  • The median progression-free survival was 9.9 months (95% CI, 4.1-not reached).
  • The results showed that SABR may be a viable option rather than CDK 4/6 inhibitor therapy.

Real-World Safety

• The Comet-5 trial (NCT02933242) assessed SABR in patients with cancer who have up to 5 oligometastases.⁶
  • The rate of grade 3 adverse effects (AEs) was 4.2% (95% CI, 2.2%-6.2%).
  • At the 2-year Kaplan-Meier analysis, the rate of grade 2 or higher AEs was 8% and 4% for grade 3 or higher.

Organs-at-Risk Doses and Constraints

• Systemic review found dose constraints from 1 to 8 fractions of SABR were collected in 33 organs-at-risk (OARs).⁷
  • The absolute allowable OAR doses showed variability.
  • No single dose constraint matched previously published results.
  • Variable organs included rectum, penile bulb, and chest wall and ribs.

References

1. Connolly E. When to consider radiation for oligoprogression. Presented at the 43rd Miami Breast Cancer Conference; March 5-8, 2026.
2. Yoon SM, Bazan JG. Navigating breast cancer oligometastasis and oligoprogression: current landscape and future directions. Curr Oncol Rep. 2024;26(6):647-664. doi:10.1007/s11912-024-01529-2
3. Ahmed KA, Scott JG, Arrington JA, et al. Radiosensitivity of lung metastases by primary histology and implications for stereotactic body radiation therapy using the genomically adjusted radiation dose. J Thorac Oncol. 2018;13(8):1121-1127. doi:10.1016/j.jtho.2018.04.027
4. Gillespie EF, Yang JC, Mathis NJ, et al. Prophylactic radiation therapy versus standard of care for patients with high-risk asymptomatic bone metastases: a multicenter, randomized phase II clinical trial. J Clin Oncol. 2024;42(1):38-46. doi:10.1200/JCO.23.00753
5. David S, Connolly E, Bressel M, et al. Stereotactic ablative body radiotherapy for oligoprogressive estrogen receptor–positive breast cancer (TROG 20.03 AVATAR): a phase II prospective multicenter trial. J Clin Oncol Adv. 2025;2(1). doi:10.1200/OA-25-00031
6. Olson R, Jiang W, Liu M, et al. Treatment with stereotactic ablative radiotherapy for up to 5 oligometastases in patients with cancer: primary toxic effect results of the nonrandomized phase 2 SABR-5 clinical trial. JAMA Oncol. 2022;8(11):1644-1650. doi:10.1001/jamaoncol.2022.4394
7. Gerhard SG, Palma DA, Arifin AJ, et al. Organ at risk dose constraints in SABR: a systematic review of active clinical trials. Pract Radiat Oncol. 2021;11(4):e355-e365. doi:10.1016/j.prro.2021.03.005