31P - Molecular mechanisms of regulation of proliferation markers of breast cancer in young patients

Abstract

Background

Complete tumor regression (stage IV) is accompanied by the highest rates of overall survival (OS): 5-year, and 15-year survival in patients of this group is 92.3% and 83.1%, respectively. In contrast, in low pathomorphism OS for the same period was 42.3% and 28.7%, respectively.

Methods

We investigated the tissue samples taken during trephine biopsies of breast tumors in 54 women with breast cancer with the mean age of 28-35 years with histologically verified malignant tumors of the mammary glands. Spectrum of markers in tissue samples comprises determination of the degree of tumor malignancy, the level of Ki-67 expression, mitotic index, and cell fraction in S-phase.

Results

We found that the most sensitive to cytotoxic drugs were proliferating pool of cells and cells in S-phase. The 3rd degree of histological malignancy, Ki 67 expression level> 30% associated with a greater probability of complete regression of tumors in response to chemotherapy. Poorly differentiated cancers are more sensitive to chemotherapy; the frequency of complete morphological effects is directly proportional to the degree of anaplasia: at tumor grades 1 and 2 the complete pathologic response rate is only 10%, but in highly aggressive tumors when chemotherapy is used it increases up to 90%. In our study, estrogen receptor status appeared an independent factor which predicted complete pathomorphological response and favorable remote results. When comparing the significance of proliferation markers, the significantly predictive value were indicators such as cell fraction in S-phase, mitotic index, the level of Ki 67. The most important value for complete pathomorphism was mitotic index: when its level was more than 17 to 3.3 mm² pCR rate reached 50%, and at the levels which were below the threshold – just 7%.

Conclusions

Thus, when mitotic index decreased significantly even at large size of residual tumor, the prognosis of the disease is relatively favorable. In cases where high mitotic index and Ki 67 index are associated with gene p53 mutation, the likelihood of significant effect of neoadjuvant chemotherapy is very low, and remote results of treatment are significantly worse.

Clinical trial indentification

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Funding

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Disclosure

All authors have declared no conflicts of interest.