Genetic evolution of breast cancer: II. relationship with estrogen and progesterone receptor expression

Summary

The expression of estrogen (ER) and progesterone (PR) receptors was assayed by steroid binding in a series of 95 malignant breast tumors, for which the analysis of chromosome aberrations was performed and allowed the reconstruction of their chromosomal evolution. It was shown that breast tumors undergo a progressive loss of chromosomes, with occasionally one and rarely two endoreduplications. Chromosome losses were often the consequence of rearrangements, and the rate of rearranged chromosomes, which increases progressively, appeared as a possible indicator of tumor progression. The distribution of ER and PR values in the sample of 95 tumors was compared to that of a larger control series of consecutive cases: 598 for ER and 460 for PR. The similarities of the distributions indicated that the sample of 95 tumors was representative of the general population of breast cancers. The levels of ER and PR expression were very strongly and negatively correlated to the rate of rearranged chromosomes, but not to the modal number of chromosomes. However, when tumors having either undergone endoreduplication or not (>50 or <51 chromosomes, respectively) were considered separately, a significant correlation between ER and PR expression and chromosome number was found within each group. Finally, breast cancers were subdivided into 4 stages of cytogenetic evolution, from the least to the most evolved: stage 1: ≤50 chromosomes, <25% rearranged chromosomes; stage 2: >50 chromosomes, <25% rearranged chromosomes; stage 3: ≤50 chromosomes, >25% rearranged chromosomes; stage 4: >50 chromsomes, >25% rearranged chromosomes. The rate of negative or low ER values (<500 fmol/g tissue) was 10% in stage 1; 16% in stage 2; 45% in stage 3; 82% in stage 4. The corresponding rates for negative or low PR values (<500 fmol/g tissue) were 17%; 28%; 60%; and 91%. These data illuminate the probable role of genetic evolution in determining the variations of biological prognostic parameters of breast cancer, such as steroid hormone receptors.