Systemic therapy of inflammatory breast cancer from high-dose chemotherapy to targeted therapies: the French experience.

BACKGROUND: Aggressiveness of inflammatory breast cancer (IBC) is related to its metastatic potential. The introduction of primary chemotherapy in the multimodality treatment has dramatically changed the prognosis. However, survival remains poor. Since 1995, innovative systemic therapies have been assessed in France in multicentric clinical trials, initially centered on high-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (HSCT), and, more recently, on targeted therapies.
METHODS: The authors present the rationale and first results of these French studies specifically dedicated to nonmetastastic IBC.
RESULTS: More than 380 patients have been included in 5 trials. The first 3 trials enrolled 329 women and concerned HDC (PEGASE 02, 05, 07). PEGASE 02 and PEGASE 05 showed a high pathological complete response rate (30%) after primary sequential HDC, and suggested that more than 4 cycles does not seem to provide any benefit. PEGASE 07 tested adjuvant maintenance chemotherapy after neoadjuvant HDC. Analysis is ongoing. The 2 other trials currently underway combine targeted therapies with conventional-dose chemotherapy in ERBB2-negative (Beverly 1 trial; bevacizumab) and ERBB2-positive (Beverly 2; bevacizumab and trastuzumab) IBC.
CONCLUSIONS: HDC with HSCT remains experimental with high pCR rates and which likely benefits to subgroups of patients that remain to be identified. Targeted therapies, such as anti-ERBB2 and antiangiogenic drugs, are being tested, and should improve survival as demonstrated in non-IBC. With emerging targeted drugs, there is hope that a cure becomes an achievable goal for more patients. Because of the rarity and the heterogeneity of disease, well-designed large-scale collaborative studies are mandatory. Copyright 2010 American Cancer Society.