High-dose Chemotherapy with Autologous Stem Cell Rescue in Stage IIIB Inflammatory Breast Cancer

Background: Despite the advances in breast cancer care, inflammatory breast cancer (IBC) has a poor prognosis. The purpose of this study was to determine the efficacy of high-dose chemotherapy (HDCT) with thiotepa, mitoxantrone and carboplatin (TMJ regimen) in women with TNM stage IIIB IBC. Patients and Methods: Between 1991 and 1998, twenty-eight patients with stage IIIB IBC underwent an autologous stem cell transplant after undergoing chemotherapy, surgery and/or radiation. Stem cells were collected from the bone marrow and periphery after mobilization with growth factors. Patients received thiotepa 250 mg/m 2 once daily i.v. for 3 days, mitoxantrone 40 mg/m 2 for 1 day and carboplatin 333 mg/m 2 once daily i.v. for 3 days as the conditioning regimen for the HDCT. Radiation therapy and tamoxifen was offered to patients post HDCT if appropriate. Progression-free survival and overall survival was assessed over a 15-year period. Results: At the time of last follow-up in May, 2007, sixteen patients had relapsed. The median overall survival was 49.5 months. The median progression free survival was 40 months. There were no transplant-related deaths. Mucositis and infections were the major side-effects. These results show that HDCT with the TMJ regimen is safe and effective in patients with stage IIIB IBC. IBC is an aggressive form of breast cancer that accounts for approximately 3-4% of all breast cancer cases (1). Conventional therapy consists of surgery, chemotherapy, local irradiation and hormonal therapy. Progression-free survival (PFS) and overall survival (OS) remain unsatisfactory, with approximately 30% of patients alive at 5 years (1). The median survival of patients with IBC is about 2.9 years (1). With improved techniques in dose-intensive chemotherapy and supportive care, there have been reports of 3-year event- free survival (EFS) for patients with IBC undergoing HDCT ranging from 42-64% (2-8). We have previously published our results with the TMJ regimen in patients with breast cancer at high risk of relapse and with metastatic breast cancer (9). We present herein our results using the same regimen in patients with stage IIIB IBC. Patients and Methods Patient selection. Patients with a clinical diagnosis of stage IIIB IBC that had been rendered free of clinically evident disease by using chemotherapy either alone or in combination with surgery or radiation were eligible for this study. The criteria for exclusion were age ≤18 and ≥60 years, performance status (ECOG) >2, prior malignancies (with the exception of cured stage I cervical cancer, non-melanoma skin cancer), infection with human immuno- deficiency virus, abnormal left ventricular ejection fraction ( 2 mg/dl or serum alanine aminotransferase levels more than three times the upper limit of normal) and a serum creatinine level more than 1.5 mg/dl. Written informed consent was obtained from the patients for the study, which was approved by the Institutional Review Board of New York Medical College. Bone marrow and peripheral blood stem cell mobilization. Bone marrow was collected from the posterior iliac crest under general anesthesia. In addition peripheral blood stem cells (PBSC) were collected following mobilization with either growth factors (GCSF or GMCSF) alone or in combination with administration of cyclophosphamide 2 g/m 2/once daily for 2 days (total dose of 4 g/m 2)