National trends and survival outcomes associated with non-guideline-concordant treatment of inflammatory breast cancer.

Purpose: National Comprehensive Cancer Network (NCCN) guidelines for inflammatory breast cancer (IBC) recommend trimodal therapy: neoadjuvant chemotherapy, modified radical mastectomy (MRM), and adjuvant radiation therapy. Historically, a minority received NCCN-guideline-concordant trimodal therapy (GCT). We explored factors associated with non-concordance, types of non-concordance, and the association of GCT with survival.

Methods: The National Cancer Database (NCDB) was analyzed for patients with non-metastatic IBC who underwent surgery from 2006 to 2019. Multivariate logistic regression identified factors associated with GCT. Cox proportional hazard models assessed the impact of GCT, and components of non-concordance, on mortality.

Results: Of 13,733 patients, 47.6% received GCT. Of non-GCT patients, 39.7% had mixed non-concordance, 25.5% exclusive chemotherapy non-concordance, 24.0% exclusive radiation non-concordance, and 10.8% exclusive surgical non-concordance. A higher burden of comorbidities, node-negative disease, and positive human epidermal growth factor receptor 2 (HER2) and hormone receptor status were associated with reduced odds of receiving GCT. GCT was associated with reduced 3-(hazard ratio [HR] = 0.83, 95% CI 0.73-0.95) and 5-year (HR = 0.83, 95% CI 0.76-0.91) mortality. Chemotherapy non-concordance and mixed non-concordance were associated with higher three-(HR = 1.28, 95% CI 1.07-1.53; HR = 1.20, 95% CI 1.01-1.43 respectively) and 5-year (HR = 1.42, 95% CI 1.26-1.60; HR = 1.17, 95% CI 1.03-1.33) mortality. Radiation non-concordance was associated with increased hazard of 1-year mortality (HR = 3.03, 95% CI 1.75-5.23). Exclusive surgical non-concordance was not associated with survival; however, simple mastectomy portended a higher hazard of 5-year mortality (HR = 1.26, 95% CI 1.08-1.46).

Conclusion: Despite improved survival, a minority of patients received GCT. Omitting neoadjuvant chemotherapy or adjuvant radiation was associated with reduced survival, whereas surgical non-concordance in patients with concordant chemoradiation did not impact survival. Simple mastectomy was associated with reduced survival, supporting the rationale for axillary lymphadenectomy.