autologous blood and marrow transplantation - Blog Science ...

248 Chapter 6: Breast Cancer
cells can contribute to relapse and influence patient outcome after high-dose
treatment. 6
Tumor cell contamination can be observed in histologically normal
bone marrow autografts in patients undergoing high-dose treatment using sensitive
immunocytochemical techniques. Peripheral blood progenitor cell (PBPC)
autografts are increasingly used in the belief that these products will have a low
probability of containing tumor cells. Recent findings confirm that although tumor
cell involvement is less extensive in PBSC autografts than in bone marrow, it is
still frequently found in PBPC collections from breast cancer patients. 7-9
Nonetheless, relapse after high-dose chemotherapy will most likely be the result
of persisting tumor cells in the patients. Consequently, detection methods for
minimal residual disease in the bone marrow before and after therapy and in
autografts are of growing importance in the evaluation of patients receiving highdose
chemotherapy with stem cell support.
Immunocytochemistry employing monoclonal antibodies (mAbs) is the most
frequently used method to detect tumor cells in bone marrow and blood. The
method should be specific, and the mAbs applied should not crossreact with normal
cells. Since the mAbs frequently used are tumor-associated and not specific against
breast cancer cells, immunostaining protocols have some limitations. The presence
of minimal residual disease in bone marrow detected by immunocytochemistry has
frequently been studied in breast cancer patients at diagnosis (Table 1). Experience
has shown that despite the need for standardization and improvement of immunocytochemical
protocols, meta-analyses confirm the presence of micrometastases in
bone marrow at diagnosis as an independent predictor of both reduced disease-free
survival and overall survival. 10-16
In Scandinavia, we have recently finished an adjuvant study in high-risk stage
II breast cancer. Patients were randomized to have dose escalation of chemotherapy
with hematopoietic growth factor or high-dose therapy with PBPC support
(Protocol FBG 9401 chaired by J. Bergh, Uppsala, Sweden). Among patients
entering this study in Norway, micrometastatic detection was performed on bone
marrow and blood before treatment, in PBPC, and on bone marrow and blood 6-12
months after treatment. Even though the observation time is short, the presence of
circulating tumor cells appears to be associated with early relapse after high-dose
therapy and stem cell support.
MATERIALS AND METHODS
Patients and high-dose therapy
Breast cancer patients with a life expectancy of less than 30% after 5 years were
randomized to have either nine cycles of dose escalation of FEC (5-fluorouracil,
epiadriamycin and cyclophosphamide) supported by subcutaneous (s.c.)