Factors predicting long-term survival for metastatic breast cancer patients treated with high-dose chemotherapy and bone marrow support

Abstract

Poor prognosis of Stage IV breast cancer patients have at best a 10% 3-year survival rate with conventional chemotherapy. Dose-intensive chemotherapy improved survival rates for some of these patients. All patients were Stage IV estrogen receptor-negative or estrogen receptor-positive hormonal refractory and received conventional chemotherapy (induction phase) to the point of achieving maximal response; if disease was stable or the patients responded, they entered high-dose chemotherapy (intensive phase). Seventy-six percent of the patients received two high-dose treatments with cyclophosphamide (4.5-6.0 g/m2), etoposide (750-1500 mg/m2), and cisplatin (120-180 mg/m2). Patients were randomized to receive or not receive autologous marrow. To identify prognostic factors for survival, univariate statistical analysis and multivariate models were applied to patient subsets. Univariate analysis identified a number of factors whose presence indicates improvement in overall survival rates. These include: (1) absence of liver relapse (P = 0.001); (2) absence of soft tissue relapse (P = 0.001); (3) a smaller number of metastatic sites at the time of detecting Stage IV disease (P = 0.026); and (4) disease-free interval greater than 1 year from initial diagnosis to Stage IV disease (P = 0.011). Multivariate models were fitted to the data, and three variables were identified as independent negative predictors for overall survival: (1) liver site (P = 0.001); (2) soft tissue site (P = 0.039); and (3) prior adjuvant chemotherapy (P = 0.028). Shorter survival after high-dose chemotherapy is predicted independently by patients pretreated with adjuvant chemotherapy, by disease distributed to the liver or the soft tissue.