Difficulties in distinguishing between locoregional and peripheral breast cancer metastases

In adjuvant therapy of breast cancer, instead of individualized chemotherap y regimens there is a tendency towards more aggressive protocols in patient s with high risk of recurrence. In this context even therapy-related mortal ity is accepted because therapy may be curative. In contrast, chemotherapy for metastatic disease mainly aims at palliation. Reduction of therapy-rela ted side effects is one of the major endpoints of clinical trials in stage IV breast cancer. Routine follow-up procedures that do not aim at early dia gnosis of metastatic disease, but at the diagnosis of symptomatic metastase s, further reflect this therapeutic strategy. During recent years this para digm has been challenged by two new developments. On the one hand, new ther apies like high-dose chemotherapy with stem-cell support may allow long-ter m survival for certain subgroups of patients with metastatic disease. On th e other hand, the refinement of diagnostic procedures may allow "metastatic disease" to be detected in breast cancer that, according to TNM staging, i s classified as early breast cancer. This and the concept of "micrometastas es" that are treated by adjuvant therapy imply that by conventional staging with chest X-ray, liver ultrasound and bone scans somehow artificially two different stages of the same disease are defined. Even if the biology of m etastasis or the refinement of diagnostic procedures is of great interest,r outine therapeutic strategies must be guided by the results from clinical t rials that mainly deal with metastatic breast cancer as defined by conventi onal staging procedures. Every modification of this definition, even if it reflects more intimate understanding of the disease, must be evaluated in p rospective randomized clinical trials.