Abstract

The current use of targeted therapy plus neoadjuvant chemotherapy for inflammatory breast cancer (IBC) is based on data extrapolated from studies in non-IBC. We conducted a systematic review to determine whether neoadjuvant chemotherapy plus targeted therapy results in a higher pathologic complete response (pCR) rate than neoadjuvant chemotherapy alone in patients with IBC. This systematic review was registered in the PROSPERO register with registration number CRD42018089465. We searched MEDLINE & PubMed, EMBASE, and EBSCO from December 1998 through July 2020. All English-language clinical studies, both randomized and non-randomized, that evaluated neoadjuvant systemic treatment with or without targeted therapy before definitive surgery and reported the pCR results of IBC patients. First reviewer extracted data and assessed the risk of bias using the Risk of Bias In Non-randomized Studies of Interventions tool. Second reviewer confirmed the accuracy. Studies were divided into 3 groups according to systemic treatment: chemotherapy with targeted therapy, chemotherapy alone, and high-dose chemotherapy with hematopoietic stem cell support (HSCS). Of 995 screened studies, 23 with 1,269 IBC patients met the inclusion criteria. For each of the 3 groups of studies, we computed a weighted average of the pCR rates across all studies with confidence interval (CI). The weighted averages (95% CIs) were as follows: chemotherapy with targeted therapy, 31.6% (26.4%-37.3%), chemotherapy alone, 13.0% (10.3%-16.2%), and high-dose chemotherapy with HSCS, 23.0% (18.7%-27.7%). The high pCR by targeted therapy group came from anti-HER2 therapy, 54.4% (44.3%-64.0%). Key limitations of this study included no randomized clinical studies that included only IBC patients. Neoadjuvant chemotherapy plus targeted therapy is more effective than neoadjuvant chemotherapy alone for IBC patients. These findings support current IBC standard practice in particular the use of anti-HER2 targeted therapy.

Highlights

  • Inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer and is associated with worse survival outcomes and prognosis than non-inflammatory breast cancer (IBC)

  • We identified no randomized clinical trial to determine the efficacy of adding targeted therapy to chemotherapy restricted to IBC patients

  • We found that the addition of targeted therapy to neoadjuvant chemotherapy for IBC patients resulted in a higher weighted-average pathologic complete response (pCR) rate

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Summary

Introduction

Inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer and is associated with worse survival outcomes and prognosis than non-IBC. IBC is defined as diffuse erythema and edema (peau d’orange) involving approximately one-third or more of the breast skin with or without an underlying palpable mass. This definition was introduced in the eighth edition of the American Joint Committee on Cancer (AJCC) [3]. The recommended approach in patients with newly diagnosed IBC is neoadjuvant systemic treatment, including chemotherapy with or without targeted therapy, followed by definitive surgery and radiation therapy [5, 6]. The current use of targeted therapy plus neoadjuvant chemotherapy for inflammatory breast cancer (IBC) is based on data extrapolated from studies in non-IBC. We conducted a systematic review to determine whether neoadjuvant chemotherapy plus targeted therapy results in a higher pathologic complete response (pCR) rate than neoadjuvant chemotherapy alone in patients with IBC

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