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GENOTOXIC FACTORS ASSOCIATED WITH THE DEVELOPMENT OF RECEPTOR-NEGATIVE BREAST CANCER: POTENTIAL ROLE OF&NBSP;THE&NBSP;PHENOMENON OF SWITCHING OF ESTROGEN EFFECTS
Aim: About 30–40% of breast cancers lack steroid receptors (ER and/or PR) at
diagnosis that worsen prognosis and limit the usage of hormone therapy. The aim of this
paper has been to study the role of DNA-damaging factors as the potential modifiers of the
receptor-negative tumors incidence. Materials and Methods: The investigation
consisted of two principal parts. In one of them ER and PR content was measured in breast
cancer samples from 2284 primary patients (350 of them — current or previous smokers).
In separately studied subgroup of 1010 patients 95 suffered with diabetes mellitus type
II. Results: As it was shown, smokers and diabetics carry more frequently (p
< 0.05) tumors with phenotypes ER+PR- and PR- only in the group of women with conserved
menstrual cycle that is in case of relatively higher estrogenic stimulation. In another
part of the investigation immunohistochemical study of DNA damage marker —
8-hydroxy-2-deoxyguanosine (8-OH-dG) in 16 R(-) and 18 R(+) breast cancer specimens
demonstrated more frequent positive staining in the former group of samples (p =
0.05). Besides, as it was revealed in breast cancer cell line MCF-7 the combination of
estradiol with aryl hydrocarbonic receptors agonist beta-naphtoflavone induced pronounced
genotoxic damage (by 8-OH-dG content) in association with the loss of ER. Conclusion:
Thus, pro-genotoxic status (smoking, diabetes) and direct signs of genotoxic injury, in
accordance with regularities of the phenomenon of switching of estrogen effects.
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