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We report on a contemporary cohort of inflammatory breast cancer (IBC) patients treated with current targeted systemic therapies selected on the basis of tumor biologic subtype. Pathologic response rates to neoadjuvant therapy along with disease-free and breast cancer-specific survival greatly varied with tumor biologic subtype. These data suggest IBC is not a distinct biologic entity transcending standard breast tumor marker subclassification.Few data exist on the influence of tumor biologic subtype on treatment response and outcomes for inflammatory breast cancer (IBC). We examined a contemporary cohort of IBC patients treated with current targeted systemic therapies, selected on the basis of tumor biologic subtype, to evaluate pathologic treatment response and cancer outcomes across biologic subtypes.We studied 57 clinical stage T4dM0 IBC patients operated on at our institution from October 2008 to July 2015. Comparisons across biologic subtypes were performed by Wilcoxon rank-sum or chi-square tests; Kaplan-Meier and log-rank tests were used to analyze survival outcomes.All patients received neoadjuvant systemic therapy; 54 (95%) completed postmastectomy radiation. Ninety-one percent (52/57) had clinically node-positive disease at presentation. Pathologic complete response (pCR) rates in the breast and axilla differed significantly by approximated biologic subtype, defined as estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER-2) negative; and HER-2 positive and ER negative/HER-2 negative (all P < .001). After 50 months' median follow-up, 20 patients experienced disease recurrence. Site of first relapse was distant in 80% (16/20). Disease-free survival (DFS) and breast cancer-specific survival (BCSS) differed significantly by biologic subtype. Five-year DFS was 46% for patients with ER-positive/HER-2–negative tumors, 82% for HER-2–positive tumors, and 33% for ER-negative/HER-2–negative tumors (P < .001), while 5-year BCSS was 76%, 100%, and 57%, respectively (P = .02)—notably better than historic reports.Our data show that both treatment response and outcomes vary significantly across IBC biologic subtypes. Multimodal treatment and modern systemic therapies have markedly improved DFS and BCSS. These data provide further evidence to suggest that IBC is not a distinct biologic entity transcending standard breast tumor marker subclassification.