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Although metastasis-directed therapy (MDT) with curative intent is increasingly added to systemic treatments in oligometastatic breast cancer (OMBC), high-level evidence to support this strategy is lacking. We aimed to evaluate the addition of MDT to systemic treatment alone (STA) in terms of progression-free survival (PFS) and overall survival (OS). Secondary endpoints were local control (LC) and toxicity. We also sought to identify prognostic factors associated with improved OS and PFS.

OMBC patients were screened from our institutional tumor board registry between 2014 and 2018. OMBC patients with ≤ 5 metastatic de novo or recurrent lesions without central nervous system involvement were included. We excluded patients with oligoprogressive disease or uncontrolled loco-regional recurrence. MDT included stereotactic body radiation therapy (SBRT), surgery, percutaneous radiofrequency ablative (PRA) and cryotherapy. Various radiation dose-fractionation schedules were used: 27Gy in 3 fractions for bone lesions, 50Gy in 5 fractions for lung tumors and 50-63.8Gy in 25-29 fractions for lymph node metastases. A Cox model with time-dependent variable was used to study the impact of MDT on PFS and OS. Sensitivity landmark analyses were also performed at 3 and 6 months.

One hundred sixty OMBC patients were identified and 102 were included (STA, n=62, MDT, n=40). Fifty two percent were synchronous oligometastatic and 48% were oligorecurrent. Most patients had only one metastasis (n=54, 52.9%). Most metastases were located in bone structures (n=100, 53.2%), lymph nodes (n=37,19.7%) and liver (n=35,18.2%). Patients had one (n=88, 86.3%) or two metastatic sites involved (n=14, 13.7%). Seventy two percent of patients had an FDG-PET/CT examination of metastatic spread. Median follow-up was 50.4 months (95% CI [44.4 ;53.4]). Five-year PFS and OS were 34.75% (95% CI [24.42;45.26]) and 63.21% (95% CI [50.69; 73.37]) respectively. Patients receiving MDT and systemic treatment had a statistically significant improved PFS and OS than those with STA ([HR 0.39, p=0.002]) and ([HR 0.31, p=0.01]). Six months Landmark analyses after the start of the first treatment showed a significant increase in PFS and OS between patients with MDT and those with STA (Figure A and B). MDT was well tolerated, only one patient presented grade 3 toxicity (pneumothorax) after PRA. Bone metastases were associated with favorable PFS and OS in univariable analysis but did not reach significance in multivariable analysis. In multivariable analysis, MDT, HER2-positive status and hormone-receptor positivity were associated with improved PFS and OS. Liver metastases led to worse PFS.

MDT seems to improve outcomes in synchronous or recurrent OMBC when added to STA without a significant increase in toxicity. The prognostic factors of PFS and OS that we identified may guide clinicians in selecting patients for MDT but need confirmation from other studies.