Proliferative indices and oncoprotein expression in benign and malignant breast biopsies

Prognostic factors are used routinely in the management of breast cancer. However, their potential for identifying precursor malignant lesions has not been assessed.

We have examined 285 breast biopsy specimens (140 benign, 145 malignant) for DNA ploidy, S-phase fraction, Ki-67 nuclear antigen proliferative indices, and HER-2/neu and epidermal growth factor receptor oncoproteins.

When proliferative indices were compared between the benign and malignant groups, differences were noted for DNA ploidy, S-phase fraction, and cell cycling index (p < 0.0005). When the benign nonproliferative specimens were compared with the atypical/proliferative benign specimens, proliferative indices failed to show any differences. When the specific subset of proliferative/atypical benign breast tissue was compared with the malignant specimens, DNA index, S-phase fraction, and cell cycling index showed significant differences. The mean for epidermal growth factor receptor was greater in the non-proliferative group but not statistically significant (p < 0.1). HER-2/neu oncoprotein failed to show any differences between the benign and malignant groups. Within the atypical benign group, Ki-67 correlated strongly with S-phase fraction and HER-2/neu (p < 0.01).

We have demonstrated that proliferative indices can differentiate between benign and malignant breast tissues but not among specific subgroups. In addition, epidermal growth factor may differentiate between nonproliferative and proliferative/atypical benign biopsy results. Oncoprotein determination, ploidy, and DNA proliferative indices may be useful in defining malignant and benign breast disease but are not useful in distinguishing between benign and malignant breast disease with an increased likelihood for malignant transformation.