Oligometastatic breast cancer represents a distinct clinical state between localized and widely metastatic disease, characterized by a limited number of metastatic lesions. Over the past decade, this concept has gained increasing attention, as advances in imaging and systemic therapy have made it possible to identify patients with a lower metastatic burden who may benefit from more aggressive local treatment strategies.
Radiotherapy has emerged as a key component in this setting. Beyond its traditional palliative role, modern techniques such as stereotactic body radiotherapy (SBRT) allow for the delivery of high, precise doses to metastatic sites with minimal toxicity. This has opened the door to potential improvements not only in local control but also in progression-free and, in selected cases, overall survival.
At the same time, the integration of radiotherapy with contemporary systemic therapies—including endocrine treatment, targeted agents, and immunotherapy—has introduced new opportunities as well as clinical challenges. Questions remain regarding patient selection, optimal timing, and treatment sequencing, highlighting the need for continued research and multidisciplinary decision-making.
Role of Radiotherapy in Oligometastatic Breast Cancer
Metastatic breast cancer has traditionally been considered an incurable condition, with treatment strategies largely focused on systemic therapy and symptom palliation. However, the recognition of oligometastatic disease has challenged this paradigm by identifying a subgroup of patients with a limited metastatic burden who may benefit from more aggressive treatment approaches. As described by Samuel Hellman and Ralph R. Weichselbaum, oligometastatic disease represents an intermediate state between localized and widely disseminated cancer, typically defined as up to five metastatic lesions in a limited number of organs.
Recent evidence suggests that metastatic breast cancer is a biologically heterogeneous disease, and outcomes vary significantly among patients. Beduk Esen et al. (2022) highlighted that patients with favorable characteristics such as younger age, hormone receptor–positive disease, limited metastatic sites (particularly bone or liver), low tumor burden, good performance status, and a long disease-free interval may derive substantial benefit from definitive treatment strategies targeting all disease sites .
In this context, radiotherapy has evolved beyond its traditional palliative role. Advances in radiation techniques, particularly stereotactic body radiotherapy (SBRT), now allow for the precise delivery of high-dose radiation to metastatic lesions while minimizing toxicity. Beduk Esen et al. (2022) reported that metastasis-directed therapies, including radiotherapy, are increasingly associated with improved local control and, in selected patients, survival outcomes.
The role of locoregional treatment of the primary tumor in metastatic disease remains controversial. While retrospective studies have suggested a survival benefit with the addition of surgery and/or radiotherapy, prospective randomized trials have produced mixed results. For example, studies have demonstrated improvements in locoregional control without consistent overall survival benefit, underscoring the need for careful patient selection and multidisciplinary decision-making.
Similarly, treating metastatic lesions directly has gained increasing interest. Because disease progression often occurs at existing metastatic sites rather than new ones, local ablative therapies such as SBRT may help delay progression. Beduk Esen et al. (2022) noted that patients with limited disease burden, good response to systemic therapy, and favorable tumor biology are most likely to benefit from these approaches.
Overall, the management of oligometastatic breast cancer is shifting toward a more individualized strategy that integrates systemic therapy with targeted local treatments. While current data are promising, ongoing prospective trials are expected to better define the role of radiotherapy and clarify which patients are most likely to benefit from aggressive, potentially curative approaches.
SBRT and Oligometastasic Breast Cancer
Oligometastatic breast cancer represents a biologically and clinically heterogeneous condition, requiring careful patient selection to optimize outcomes with local therapies. Colciago et al. (2025) emphasize that, although stereotactic body radiotherapy (SBRT) has emerged as an effective ablative treatment, its benefit is not uniform across all patients, highlighting the importance of individualized treatment strategies.
SBRT has demonstrated consistently high rates of local control with minimal toxicity across multiple studies. Colciago et al. (2025) report that observational and prospective data show local control rates approaching 70–100%, with many patients achieving durable disease stabilization and remaining progression-free for extended periods . However, despite these promising local outcomes, randomized trials have not consistently demonstrated improvements in progression-free or overall survival, underscoring the complexity of translating local control into long-term clinical benefit.
A key determinant of outcome is the number of metastatic lesions. Patients with a single metastasis appear to derive the greatest benefit from SBRT. For example, Milano et al. demonstrated improved progression-free survival in patients with a solitary lesion compared with those with multiple metastases, while Weykamp et al. also identified single metastasis as a favorable prognostic factor (Colciago et al., 2025) . Although some studies show conflicting results, the overall trend supports better outcomes in patients with lower disease burden.
The site of metastasis also plays a critical role. Bone-only disease is consistently associated with improved outcomes, whereas visceral metastases—particularly liver involvement—are linked to poorer survival. Colciago et al. (2025) highlight that patients with bone-only oligometastatic disease demonstrate superior progression-free and overall survival compared with those with extra-osseous disease.
Biomarkers and Oligometastatic Breast Cancer
Tumor biology further influences prognosis. Hormone receptor–positive disease is generally associated with better outcomes, while triple-negative breast cancer carries a significantly worse prognosis. In a large population-based analysis, triple-negative subtype was associated with markedly reduced overall survival, whereas HER2-positive disease showed more favorable outcomes, likely reflecting the availability of effective targeted therapies (Colciago et al., 2025) .
Other important factors include disease-free interval, prior systemic therapy, and performance status. A longer disease-free interval—typically greater than 24 months—is associated with improved survival, suggesting a more indolent disease biology. Additionally, patients who are treatment-naïve or have received fewer lines of systemic therapy tend to have better outcomes, while good performance status remains an important predictor of response to treatment (Colciago et al., 2025) .
Emerging biomarkers may further refine patient selection. Circulating tumor DNA (ctDNA), gene expression profiles, and immunologic markers such as GM-CSF are being investigated as potential predictors of response and survival. Although early data are promising, Colciago et al. (2025) note that these approaches require validation in prospective studies before routine clinical implementation.
Metastasis-Directed Therapy in Oligometastatic Breast Cancer
The potential role of metastasis-directed therapy in oligometastatic breast cancer remains an area of active investigation, particularly given conflicting evidence from randomized studies. While earlier trials in other solid tumors suggested a benefit from combining local ablative therapy with systemic treatment, results in breast cancer have been less consistent.
Reddy et al. (2024) conducted the EXTEND trial, a multicenter randomized phase II study evaluating whether the addition of metastasis-directed therapy (MDT) to standard-of-care systemic therapy improves outcomes in patients with oligometastatic breast cancer. Patients with up to five metastatic lesions were randomized to receive either systemic therapy alone or systemic therapy combined with definitive local treatment to all sites of disease .
The study did not demonstrate a benefit from the addition of MDT. Median progression-free survival was not improved in the MDT arm compared with systemic therapy alone (15.6 vs 24.9 months; hazard ratio 0.91, p = 0.86) . Similarly, no significant differences were observed in overall survival, time to initiation of subsequent systemic therapy, or the development of new metastatic lesions.
Importantly, the addition of MDT did not negatively impact quality of life or increase toxicity, suggesting that the approach is safe but may not provide additional systemic benefit in an unselected patient population. Furthermore, no meaningful differences were observed in immune-related outcomes, including T-cell activation or cytokine profiles, indicating that MDT did not enhance systemic immune response in this setting .
Reddy et al. (2024) conclude that, in patients with oligometastatic breast cancer, the addition of metastasis-directed therapy to standard systemic treatment does not improve key clinical outcomes. These findings reinforce the importance of careful patient selection and suggest that the routine use of MDT in all oligometastatic breast cancer patients may not be justified without further stratified evidence.
Written By Aren Karapetyan, MD