MOLECULAR CHANGES AND TARGETED THERAPY IN INFLAMMATORY BREAST CANCER

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Abstract

Inflammatory breast cancer (IBC) is one of the most aggressive subtypes of breast cancer. IBC represents 2%–4% of breast cancer, but it represents 10% of breast cancer-related mortality. Despite multimodality approaches, the prognosis for patients with this disease remains poor. Although we are making efforts to improve treatment for IBC, IBC research remains to be limited because this is a rare disease and there are few defined targets for IBC due to undefined IBC biology.

To improve this situation, we require insights from clinical trials and epidemiologic studies investigating IBC biology. Molecular targets such as vasculolymphatic, proliferation, and metastatic process has been identified, but all of these unique targets require clinical validation by clinical trials.

Molecular targets in cell proliferation processes have been investigated the most and have yielded promising clinical results leading to improved outcomes for patients with IBC. These cell proliferation targets include HER2 and EGFR. As was the case in non-IBC, the HER2 antibody trastuzumab dramatically changed the prognosis of patients with HER2-overexpressing IBC. Lapatinib, which inhibits both HER2 and EGFR, also showed benefit in patients with HER2-positive breast cancer, including IBC, in clinical trials. Additional cell proliferation targets—WISP3, RhoC GTPase, and p27kip1—have also been studied in IBC.

Molecules involved in metastasis processes may have a unique role in IBC owing to the aggressiveness of this disease. E-cadherin has been observed to be overexpressed in IBC, and loss of E-cadherin is a hallmark of epithelial-mesenchymal transition (EMT). Although this E-cadherin overexpression might be a transient phenomenon, we may be able to target this unique feature. Other potential candidate is the EGFR pathway. We have been investigating the role of this pathway and the possibility of EGFR-targeted therapy for IBC. We are conducting a clinical trial with panitumumab, a human EGFR antibody, plus chemotherapy (nab-paclitaxel and carboplatin) as a preoperative regimen in patients with HER2-negative IBC.

In summary, further extensive preclinical and clinical work based on molecular findings is needed to improve outcomes in patients with IBC.

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