[Systemic treatments of inflammatory breast cancer: an overview]

Abstract

The poor prognosis of inflammatory breast cancer (IBC) is due to its strong metastatic potential. During the last three decades, the introduction of neoadjuvant chemotherapy (CT), and its improvement with successive additions of anthracyclines and then taxanes, allowed to double the survival. However, the 5-year survival still remains lower than 50%, with the pathological complete response (pCR) to neoadjuvant CT being a major prognostic factor. Since 1995, several innovative approaches have been evaluated. Initially, the trials of high-dose CT with hematopoietic stem cell transplantation have generated promising results, but ultimately failed to change standards of treatment, in particular because of its toxicity. More recently, a few targeted therapies, combined to conventional CT, have been assessed, due to the frequent overexpression of HER2 and EGFR and the important vascularization of IBC. Trastuzumab, a monoclonal antibody targeting HER2, has shown a clear advantage in terms of pCR and survival in studies dedicated to, HER2-positive locally advanced breast cancers, including IBC. Lapatinib, a dual tyrosine kinase inhibitor anti-HER2 and EGFR, has shown significant activity in two phase II studies dedicated to HER2-positive IBC. The interest of HER2-double blockade by the combination of trastuzumab-pertuzumab combined to docetaxel has been demonstrated in term of pCR in the NEOSPHERE study which also included HER2-positive IBC. Among the anti-angiogenic drugs tested in studies dedicated to IBC, bevacizumab has given the most interesting results in term of efficacy/toxicity ratio. In the Beverly 2 study HER2-positive IBC patients were treated by the combination chemotherapy, trastuzumab and bevacizumab: the rate of pCR was 64%, and the 3-year disease-free and overall survivals were 68% and 90%, respectively; the increase of endothelial cells circulating was inversely correlated to the probability of pCR. All those treatments have been extrapolated from standard breast cancers. Thus, a deep molecular knowledge of IBC appears to be critical in order to develop specific treatments effectively targeting its particular aggressiveness.

Keywords: anthracyclin; bevacizumab; chemotherapy; inflammatory breast cancer; lapatinib; pertuzumab; taxanes; trastuzumab.