Summary: DNA flow cytometric monitoring of spontaneous and therapy-induced clonal evolution of breast cancer. Flow cytometric DNA profiles may be useful in quantitative estimation of the degree of genomic instability and in the description of tumor evolution during progression and therapy. The distribution of different types of DNA profile was almost identical among 160 node negative a and 136 node positive operable breast cancers with DNA diploidy, tetraploidy and aneuploidy in 46%, 25%, 29% and 46%, 22%, 32% respectively. The DNA ploidy pattern is unrelated to metastatic capacity of breast cancer. However, the comparison of DNA profiles between primary tumors and lymph node metastases of 92 breast cancer, which may reflect clonal evolution of tumor, revealed stability in 70% (64/92), loss of aneuploidy in 22% (20/92) and rare spontaneous diversification from DNA diploidy to aneuploidy in only 8% (8/92). Chemotherapy increased the proportion of diversifying breast cancers up to 29% (4/14), while no such tendency could be seen after radiotherapy alone in direct as well as in indirect comparisons. Radiotherapy combined with endocrine treatment was associated with disappearance of DNA aneuploid subpopulation in 55% (5/9) cases. Since the aneuploid DNA profile is considered to be associated with higher proliferation and increased tumor aggressivity, chemotherapy may not be beneficial in individual cases which express newly-developed, chemotherapy-induced aneuploid populations. We hypothesize, that the monitoring of tumor DNA profiles during therapy of partially and/or poorly-responding breast cancers may help to identify cases in which further chemotherapy might be regarded as detrimental.
DNA flow-cytometric monitoring of spontaneous and therapy-induced clonal evolution of breast cancer
