Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-institutional Registry Study-IMET, Protocol MF 14-02.

BACKGROUND: One fourth of early-stage breast cancer cases become metastatic during the follow-up period. Limited metastasis is a metastatic disease condition in which the number of metastatic sites and the extent of the disease both are limited, and the disease is amenable to metastatic intervention. This prospective study aimed to evaluate intervention for limited metastases in the lung, liver, or both. METHODS: The study enrolled luminal A/B and/or human epidermal growth factor receptor 2 (HER2)-neu+ patients with operable lung and/or liver metastases in the follow-up assessment after completion of primary breast cancer treatment and patients with a diagnosis of metastasis after 2014. Demographic, clinical, tumor-specific, and metastasis detection-free interval (MDFI) data were collected. Bone metastasis in addition to lung and liver metastases also was included in the analysis. The patients were divided into two groups according to the method of treatment for metastases: systemic therapy alone (ST) group or intervention (IT) group. RESULTS: Until June 2020, 200 patients were enrolled in the study. The demographic data were similar between the two groups. The median follow-up time was 77 months (range 55-107 months) in the IT group (n = 119; 59.5%) and 57 months (range 39-84) in the ST-only group (n = 81; 40.5%). The median MDFI was 40 months (range 23-70 months) in the IT group, and 35 months (range 13-61 months) in the ST-only group (p = 0.47). The groups had similar surgeries for the primary tumor and axilla. Most of the patients had liver metastases (49.5%, n = 99), and 42% (n = 84) of the patients had lung metastases. Both lung and liver metastases were found in 8.5% (n = 17) of the patients. The primary tumor was estrogen receptor/progesterone receptor-positive in 75% (n = 150) of the patients, and 32% (n = 64) of the patients had HER2-neu+ tumors. Metastatic-site resection was performed for 32% (n = 64) of the patients, and 27.5% (n = 55) of the patients underwent metastatic ablative interventions. In the Kaplan-Meier survival analysis, the hazard of death (HoD) was 56% lower in the IT group than in the ST-only group (hazard ratio [HR], 0.44; 95% confidence interval [CI] 0.26-0.72; p = 0.001). The HoD was lower in the IT group than in the ST-only group for the patients younger than 55 years (HR, 0.32; 95% CI 0.17-0.62; p = 0.0007). In the multivariable Cox regression model, HoD was significantly lower for the patients who underwent intervention for metastases and had an MDFI longer than 24 months, but their liver metastases doubled the risk of death compared with lung metastases. CONCLUSION: Metastasis-directed interventions have reduced the risk of death for patients with limited lung/liver metastases who are amenable to interventions after completion of primary cancer treatment. For a select group of patients, such as those with luminal A/B or HER2-neu+ breast cancer who are younger than 55 years with limited metastases to the lung and liver or an MDFI longer than 24 months, surgical or ablative therapy for metastases should be considered and discussed on tumor boards.