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The purpose of this article review is to discuss the current adjuvant approach for human epidermal growth factor receptor 2 (HER2) gene amplification or overexpression inflammatory breast cancer (IBC), as well as promising therapies to improve the prognosis of these patients, with the main focus on the high risk setting of patients with residual disease after neoadjuvant therapy.IBC is a rare and very aggressive form of breast cancer. HER2+ is more frequent in IBC than in non-IBC. A combined multimodality therapy is essential for better outcomes in non-metastatic HER2+ IBC patients, including neoadjuvant chemotherapy, with dual HER2 blockade, local therapy with surgery and radiotherapy, and adjuvant systemic therapy, which is defined on the basis of pathological response and hormone receptor (HR) status. Dual HER2 blockade with trastuzumab and pertuzumab combined to neoadjuvant chemotherapy improved the pathological complete response (pCR) rate. However, HER+ IBC patients with residual disease at surgery have a high risk of recurrence and death.A comprehensive review was conducted through Medline/PubMed database, ClinicalTrials.gov, and conference abstracts.Escalation of adjuvant therapy for patients with HER2+ IBC with residual invasive disease after neoadjuvant therapy is recommended. Adjuvant ado-trastuzumab emtansine and neratinib, for HR+ disease, are the most recent advances in this setting, with a clinically meaningful improvement in invasive disease-free survival (iDFS). Despite the clinical advances, reducing the risk of central nervous system recurrence remains an unmet need. Several promising clinical trials are ongoing to improve patients' prognosis in this high-risk of recurrence setting.