Trends in Surgical Treatment for cT4 Breast Cancer After Neoadjuvant Systemic Therapy: A Nationwide Study in The Netherlands

Background: Current guidelines recommend neoadjuvant systemic therapy (NST) followed by modified radical mastectomy (MRM) for stage T4 breast cancer. In this study, trends in MRM and de-escalated surgery of cT4a-c and cT4d breast cancer were evaluated and the impact of treatment on survival was assessed.

Methods: Patients with cT4N_anyM0 breast cancer who received NST between 1989 to 2020 were selected from the Netherlands Cancer Registry. Rates of MRM and de-escalated breast/axillary surgery were analyzed for the periods 1989–1999, 2000–2009, and 2010–2020. Cox proportional hazard regression with inverse probability weighing was used to estimate for confounding-adjusted hazard ratios (HRs) for overall survival. Crude relative survival was calculated using excess mortality ratios from national life tables.

Results: This study included 2,541 patients with cT4a-c and 1479 with cT4d breast cancer. The frequency of MRM decreased from 78% in 1989–1999 to 54% in 2010–2020 for cT4a-c and from 82% to 70% for cT4d patients. De-escalated surgery was associated with better overall survival than MRM, for both cT4a-c (HR 0.74, 95% confidence interval [CI] 0.63–0.87) and cT4d breast cancer (HR 0.78, 95% CI 0.63–0.96). Five-year crude relative survival for MRM versus de-escalated treatment was 66% (95% CI 0.64–0.69) versus 83% (95% CI 0.79–0.87) for cT4a-c, and 56% (95% CI 0.53–0.59) versus 70% (95% CI 0.64–0.76) for cT4d.

Conclusions: Modified radical mastectomy rates decreased over time. De-escalated surgery was associated with improved 5-year overall survival compared with MRM. These findings suggest that de-escalated surgery is at least equivalent to MRM in terms of survival and may support consideration of less invasive surgical approaches.