Primary tumor resection is associated with improved survival in de novo lung metastatic breast cancer

The role of primary tumor resection (PTR) in patients with de novo stage IV breast cancer remains controversial, and evidence from randomized trials is inconsistent. Whether PTR is associated with improved survival in clinically defined subgroups such as lung-only metastatic disease warrants further investigation. Using the SEER database, we identified patients diagnosed with stage IV breast cancer between 2010 and 2020 with metastases confined to the lungs at diagnosis. Patients with bone, liver, brain, or other distant metastases were excluded. Overall survival (OS) and breast cancer-specific survival (CSS) were estimated using Kaplan-Meier methods and compared by log-rank tests. Cox proportional hazards models were used to evaluate factors associated with OS. Temporal trends in PTR utilization and year-specific survival were examined. Predictors of receiving PTR were assessed using multivariable logistic regression. A total of 1,479 eligible patients were included; 588 (39.8%) underwent PTR and 891 (60.2%) did not. Median OS was 48 months in the PTR group versus 30 months in the no-surgery group. Median CSS was 53 months versus 33 months, respectively. On multivariable Cox regression, primary tumor resection was associated with improved OS (HR 0.63, 95% CI 0.54-0.73; P < 0.001). The annual PTR rate decreased from 58.1% in 2010 to 25.6% in 2020, while estimated 3-year OS increased from 38.5% (2010) to 55.7% (2019). In multivariable logistic regression, PTR was more likely among patients with young-onset breast cancer (YBC) status (adjusted OR 1.67, 95% CI 1.08-2.56; P = 0.020) and those receiving radiation therapy (adjusted OR 26.47, 95% CI 16.81-43.84; P < 0.001), but less likely in later diagnosis years (2014-2017: adjusted OR 0.55, 95% CI 0.41-0.73; P < 0.001; 2018-2020: adjusted OR 0.36, 95% CI 0.26-0.50; P < 0.001). In this selected cohort of chemotherapy-treated patients with de novo stage IV breast cancer and lung-only metastasis, PTR was associated with longer OS and CSS. However, this association should be interpreted cautiously, as lung-only metastatic disease may represent a surrogate marker of favorable disease biology and treatment selection. Given the observational nature of the study, the findings should be regarded as hypothesis-generating rather than practice-changing and warrant prospective validation in carefully selected patients.