Chemotherapy response and survival of inflammatory breast cancer by hormone receptor- and HER2-defined molecular subtypes approximation: an analysis from the National Cancer Database

Purpose: To study the impact of hormone receptor (HR)- and human epidermal growth factor receptor 2 (HER2)-defined subtypes on survival of inflammatory breast cancer (IBC), and to determine whether sensitivity to neoadjuvant chemotherapy (NAC) varies with subtypes in a large IBC population. Methods: We analyzed 593 IBCs with known HR/HER2 statuses between 2010 and 2011 from National Cancer Database. We compared pathologic complete response (pCR) rates among four molecular subtypes by Chi-square test. Overall survival (OS) was compared among four subtypes and patients with or without pCR using log-rank test. Multivariate Cox model was performed to identify the impact of molecular subtype and other prognostic factors on OS. Results: Of the 593 patients included, 231 (39.0 %) patients had HR+/HER2− tumors, 98 (16.5 %) had HR+/HER2+ disease, 112 (18.9 %) were HR-/HER2 + patients, and 152 (25.6 %) had triple-negative subtype. The pCR rates differed significantly by subtype (P < 0.001): HR−/HER2+ showed the highest, and HR+/HER2− exhibited the lowest. Multivariate analysis showed that triple-negative and HR+/HER2− IBCs had significantly worse survival compared with HR+/HER2+ or HR−/HER2+ subtype (P < 0.01 for all comparisons). Additional factors associated with worse OS included more comorbidities, lack or incomplete surgical resection, absence of radiotherapy, lack of hormone therapy, and more advanced stage. Conclusions: IBC is an aggressive heterogeneous disease with distinct molecular subtypes associated with differential outcomes and sensitivities to NAC. Unlike in noninflammatory breast cancer, in IBC HR + disease was not associated with favorable prognosis. Triple-negative and HR+/HER2− subtypes are independent predictors for suboptimal OS in IBC.