The optimization of postoperative radiotherapy in de novo stage IV breast cancer: evidence from real-world data to personalize treatment decisions

Abstract

Prolonged survival of patients with stage IV breast cancer could change the role of radiotherapy for local control of breast primary, but its survival benefit remains unclear. Our aim is to investigate the survival benefit of radiotherapy in de novo stage IV breast cancer. Stage IV breast cancer patients who received breast surgery and have survived 12 months after diagnosis (landmark analysis) were included in the study from 2010 to 2015 of the National Cancer DataBase. Multivariable Cox models and a propensity score matching were used to control for confounding effects. Of 11,850 patients, 3629 (30.6%) underwent postoperative radiotherapy to breast or chest wall and 8221 (69.4%) did not. In multivariable analysis adjusting for multiple prognostic variables, postoperative radiotherapy was significantly associated with better survival (hazard ratio [HR] 0.74, 95% confidence interval [95%CI] 0.69-0.80; P < 0.001). Radiotherapy was associated with improved survival in patients with bone (P < 0.001) or lung metastasis (P = 0.014), but not in patients with liver (P = 0.549) or brain metastasis (P = 0.407). Radiotherapy was also associated with improved survival in patients with one (P < 0.001) or two metastatic sites (P = 0.028), but not in patients with three or more metastatic sites (P = 0.916). The survival impact of radiotherapy did not differ among subtypes. The results of survival analysis in the propensity score-matched sub-cohort were precisely consistent with those of multivariable analysis. These real-world data show that postoperative radiotherapy might improve overall survival for de novo Stage IV breast cancer with bone or lung metastasis, regardless of subtypes.

Figure 1

Consort diagram of cohort selection in National Cancer Database (NCDB).

Figure 2

The forest plots showed the hazard ratio (HR) and 95% confidential interval (CI) of radiotherapy in selected subgroups after adjusting for prognostic variables (age, race, Charlson-Deyo comorbidity index, clinical T stage, clinical N stage, grade, subtype, surgery type, chemotherapy, endocrine therapy, bone, lung, liver, brain metastasis and the number of metastatic sites) in multivariable Cox models. LN lymph node, HER2 human epidermal growth factor receptor 2, TN triple negative.

Figure 3

Overall survival of patients with or without radiotherapy in the overall propensity score matched cohort (A), the subgroups of bone metastasis (B), lung metastasis (C), liver metastasis (D), brain metastasis (E), and bone + /− distant lymph node metastasis (F). Log-rank test was used to test the significance of survival difference and P values were shown in the figure. In Cox regression models, radiotherapy was significantly associated with improved survival in the overall cohort (HR 0.76, 95% CI 0.71–0.82; P < 0.001) (A), with bone metastasis (HR 0.74, 95% CI 0.67–0.82; P < 0.001) (B), lung metastasis (HR 0.77, 95% CI 0.66–0.91; P = 0.002) (C) or bone + /− distant lymph node metastasis (HR 0.73, 95% CI 0.65–0.82; P < 0.001) (F), but not in patients with liver metastasis (HR 0.85, 95% CI 0.71–1.01; P = 0.093) (D) or brain metastasis (HR 0.94, 95% CI 0.57–1.55; P = 0.803) (E). HR, hazard ratio; CI, confidence intervals.

Figure 4

Overall survival of patients with or without radiotherapy in the subgroups of 1 metastatic site (A), 2 metastatic sites (B), 3 or more metastatic sites (C), Luminal subtype (D), HER2 + subtype (E), and triple-negative subtype (F) in the overall propensity score matched cohort. Log-rank test was used to test the significance of survival difference and P values were shown in the figure. In Cox regression models, radiotherapy was significantly associated with improved survival in patients with 1 metastatic site (HR 0.75, 95% CI 0.68–0.81; P < 0.001) (A), or 2 metastatic sites (HR 0.79, 95% CI 0.66–0.94; P = 0.007) (B), but not in patients with 3 or more metastatic sites (HR 0.98, 95% CI 0.68–1.41; P = 0.981) (C). Radiotherapy was also significantly associated with improved survival in patients with Luminal subtype (HR 0.74, 95% CI 0.66–0.82; P < 0.001) (D), HER2 + subtype (HR 0.74, 95% CI 0.63–0.88; P < 0.001) (E) and triple-negative subtype (HR 0.78, 95% CI 0.66–0.92; P = 0.003) (F). HR, hazard ratio; CI, confidence intervals.