This represents the first report on the clinical activity and long-term outcome of trastuzumab-based regimens in IBC. The retrospective study confirmed the significant increase in pCR compared to historical controls in the subset of patients with HER-2/neu-amplified disease. Moreover, we demonstrated that this cohort of patients continues to have a risk of recurrence in the chest wall and, relatively early recurrence in the brain in spite of high pCR. These data suggest that IBC patients treated with preoperative, trastuzumab-based regimens may need additional postoperative treatment modalities to significantly modify long-term outcome.
The goal of improving pCR in IBC requires the introduction of HER2 targeted therapies in neoadjuvant setting. Few prospective clinical trials among patients with HER-2/neu-positive disease where trastuzumab was incorporated into preoperative chemotherapy regimens, have reported pCR rates ranging from 12% to 23% (14
). Hurley et al.
) achieved a pCR rate of 17% in a cohort of 48 patients with HER-2/neu-positive LABC (including four patients with IBC) who received 12 weeks of preoperative treatment with a combination of docetaxel, cisplatin and trastuzumab. The largest experience was reported by Baselga et al.
) with the preliminary data of the NOAH (Neoadjuvant Herceptin) phase III trial evaluating the addition of trastuzumab in the neoadjuvant treatment of LABC, including IBC. They observed a significant improvement of pCR rate (54.8% versus 19.3%, with and without trastuzumab, respectively, p = 0.002) in 31 HER-2 positive IBC patients treated with three cycles of neoadjuvant doxorubicin-paclitaxel (AT), four cycles of paclitaxel and three cycles of cyclophosphamide/methotrexate/5-fluorouracil (CMF).
Another important preliminary observation, to be confirmed in larger series, is the role of chemokines, particularly how the CXCR4/SDF1 axis can contribute to the homing of breast cancer cells to the brain. It has been recently suggested that expression of CXCR4 could be regulated by HER-2/neu by increasing the expression of CXCR4, which is required for HER-2/neu-mediated invasion in vitro and lung and brain metastases in vivo (17
In conclusion, trastuzumab-based regimens are extremely active and well tolerated in patients with newly diagnosed IBC. Despite initial response, early recurrence continues to be a reality with biology of disease probably implicated in distant failure involving the brain. The use of combined adjuvant modalities with agents able to affect the metastatic process or the use of novel HER-2 targeted therapies with tyrosine-kinase inhibitors such as lapatinib may represent a rational approach to further improve the prognosis of patients with IBC (18