Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis

Aims and background: The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. Methods: DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. Results: Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time to progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G₁ (well-differentiated) G₂ and G₃, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G_1-2 than G₃ tumors with the logrank test (P <0.03) and multivariate analysis. Conclusions: Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.