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The role of high-dose chemotherapy (HDCT) in patients with refractory breast cancer is not well established. Forty-two female patients (median age of 46 years) with breast cancer refractory to neoadjuvant chemotherapy received HDCT (cyclophosphamide, carmustine and thiotepa) supported by an autologous peripheral blood stem cells transplant. Their disease had been refractory (defined as less than partial response) to one (18 patients) or two (24 patients) regimens of neoadjuvant chemotherapy. Twenty-nine patients had surgery before HDCT. The best response after surgery, HDCT, and radiation therapy was assessed 60 days after transplantation. Thirty patients had complete remission, eight had a PR, one had a minor response, and three had progressive disease. In seven of 13 patients whose disease was inoperable before HDCT, it became operable. After a median follow-up of 42 months, 21 patients were alive, and 15 remained disease free. Five-year overall survival (OS) was 57% (CI, 50-64%), and the estimated 5-year progression-free survival was 40% (CI, 32-48%). Both OS and PFS were better in patients whose disease became operable after chemotherapy than in those whose disease remained inoperable. A randomized study is warranted in this patient population.

We assessed the 5-year results of a high-dose cyclophosphamide, carmustine, and thiotepa (CBT) regimen plus autologous hematopoietic stem cell transplantation (AHST) as an adjuvant consolidation therapy for high-risk primary breast cancer patients with > or =10 positive axillary lymph nodes after primary surgery or > or =4 positive axillary lymph nodes after neoadjuvant chemotherapy and surgery. The associations of various potential prognostic factors with the relapse-free survival (RFS) rate and overall survival (OS) rate were determined. Between October 1992 and March 2000, 177 eligible patients (median age, 46 years) were given high-dose CBT followed by AHST. At a median follow-up of 63 months, the acute treatment-related mortality was 4.5%. Estimated 5-year RFS and OS rates were 62% and 68%, respectively, for all patients. For patients with > or =10 positive axillary lymph nodes after primary surgery, the 5-year RFS and OS rates were 71% and 70%, respectively, and for patients with > or =4 positive axillary lymph nodes after neoadjuvant chemotherapy, the 5-year RFS and OS rates were 53% and 66%, respectively. In 2-sided log-rank tests, earlier disease stage, a lower lymph node ratio, and a lower tumor score were associated with a prolonged RFS and OS. In a multivariate proportional hazards model, disease stage and lymph node ratio remained significant. We concluded that high-dose CBT with AHST for high-risk primary breast cancer is feasible, with comparable efficacy to other phase II studies. More than a 50% estimated 5-year survival rate was seen in all high-risk primary breast cancer patients. In accordance with results from recent randomized studies, we need to continue high-dose chemotherapy with AHST for patients with high-risk primary breast cancer in the phase III randomized setting.

The aim of this study was to study the effectiveness of the Swenerton score in assessing extent of disease as an independent prognostic and predictive factor in patients with metastatic breast cancer (MBC) who receive high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplant (AHSCT). Two-hundred thirty-two patients with MBC underwent HDCT. Extent of disease was assessed quantitatively using the Swenerton score. A retrospective analysis was performed using Cox proportional hazards regression and logistic regression models. One hundred three (44%) patients had a complete response (CR) after HDCT. Bone marrow as source of hematopoietic stem cells, hormone-receptor-negative status, and visceral involvement correlated with both worse overall survival (OS) and progression-free survival (PFS). Short disease-free interval, multiple sites of metastatic disease, and less than 50% reduction in the Swenerton Score during induction chemotherapy correlated with worse OS. Patients in CR at the time of HDCT had better PFS than patients in partial response, stable disease, or progressive disease. Fifty-six patients who underwent conversion to CR after HDCT had a similar median OS (not reached v 74 months; P =.51) and PFS duration (22 v 44 months; P =.15) as patients who received HDCT after a CR to standard-dose chemotherapy (SDCT). Conversion to CR was predicted by a >/=50% reduction in the Swenerton score during SDCT (odds ratio [OR] 3.32, P <.01) and soft-tissue disease (OR 4.08, P <.01). The presence of multiple metastatic sites predicted decreased probability of conversion to CR (OR 0.34, P <.01). The Swenerton score provides a thorough estimate of disease extent, and reduction of Swenerton score by SDCT is potentially useful for selecting the optimal candidates for HDCT trials who may achieve long-term disease control.