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Prognostic and Predictive Factors for Patients With Metastatic Breast Cancer Undergoing Aggressive Induction Therapy Followed by High-Dose Chemotherapy With Autologous Stem-Cell Support

From the Duke University Medical Center Marrow and Stem Cell Transplantation Program, Durham, NC.

Address reprint requests to David A. Rizzieri, MD, Division of Oncology and Bone Marrow Transplantation, Box 3961, Duke University Medical Center, Durham, NC 27710; email rizzi003{at}mc.duke.edu

PURPOSE: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy.

PATIENTS AND METHODS: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses.

RESULTS: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P = .0041), smaller metastatic foci ( 2 v > 2 cm) (P = .0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases ( 2 v > 2 years) (P = .0051), and prior treatment with tamoxifen (P = .0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P = .0001) and those who developed liver metastases (P = .0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P = .0006), as did patients who had received prior adjuvant therapy (P = .0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P = .0143).

CONCLUSION: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive–patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.

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