Breast cancer is one of the major causes of cancer deaths in women worldwide . As the malignancy of tumors increases, the body's hypercoagulable state may be a response to tumor cell invasion and metastasis . Patients with advanced breast cancer have significantly increased coagulation abnormalities and thromboembolic events, which are important factors affecting the quality of life and survival outcomes of patients .
It has been reported in the literature that approximately 50% of cancer patients and 94% of metastatic patients exhibit abnormal coagulation/fibrinolysis system indicators [18, 19]. In our study, we observed that the HCY level was abnormally increased in breast cancer patients. When comparing the abnormality rate, we also found that the abnormality rate of HCY in the patient group was higher than that in the control group, compared with Hasan T, Rehman T, etc. The research results [8, 20] are consistent. Wu et al. . showed that in premenopausal and postmenopausal women, high concentrations of HCY mainly play a pathogenic role through the metabolic accumulation of intracellular SAH. SAH is a catechol-O-methyltransferase(COMT)-mediated endogenous and exogenous catechin, which is a strong non-competitive inhibitor of phenol methylation metabolism. The oxidative metabolites of estrogen, including catechol estrogen and 16a-OHE1, are involved in the development of estrogen-induced tumors and human breast cancer in some animal models. COMT methylation is the inactivation of catechol estrogen. Therefore, when we analyzed the HCY levels of patients on different menstrual status, we found that the HCY levels in the postmenopausal group were significantly higher than those in the control group. Research on HCY and breast cancer risk factors found that HCY level is associated with a higher risk of breast cancer, and the higher the HCY level, the higher the risk of breast cancer. HCY can be used as an independent factor of breast cancer risk. Subsequently, we grouped breast cancer patients with different TNM stages and found that in the premenopausal patient group, the HCY level of T2-T3 patients was significantly higher than that of Tis-T1 patients. Thus, the hormone levels in the patients may affect the HCY levels in the body. Thereby affecting the size of the tumor. However, the mechanism needs to be studied in further. In its molecular typing study, it was found that the abnormal rate of HCY in triple-negative breast patients was higher than that of LuminalA + B group and HER-2 overexpression group, which was consistent with the results of Naushad SM et al.. In the study of the coagulation/fibrinolysis system indicators, it was found that the levels of PT, AT-III, PC, F-VIII, and α2-AP were lower in the breast cancer patient group than in the control. The levels of Fbg and D-D in the breast cancer patient group were significantly higher than those in the control group. The levels of AT-III, PC and α2-AP in the premenopausal group were significantly reduced in breast cancer patients; the levels of F-VIII and α2-AP in the postmenopausal group showed a decreasing trend in breast cancer patients. The levels of Fbg and D-D showed a significant increase in breast cancer patients in the postmenopausal group. The abnormal rate of PT, ATPP, FDP, and D-D in the breast cancer patient group was significantly higher than that of the control group, and the abnormal rate of F-VIII and α2-AP in the breast cancer patient group was significantly lower than that of the control group. In the study of the correlation between the coagulation/fibrinolysis system indicators and the risk of breast cancer, we found that PT, Fbg, AT-III, PC, F-VIII, α2-AP, FDP, D-D, PLT were independent factors related to the risk of breast disease. We analyzed breast cancer patients with different TNM stages and found that in T stage, breast cancer patients with Tis-T1 stage had higher PT and ATPP levels than those with T2-T4 stages; The levels of Fbg, AT-III, PC, α2 -AP, FDP and D-D are higher in patients with stage T2-T4 than those with stage Tis-T1, indicating that the increase in coagulation/fibrinolysis index levels may be related to the size of the tumor. In the N stage, the levels of Fbg, AT-III, and α2-AP are higher in N1-N3 stage patients than in N0 stage patients, which is consistent with the results of Yu et al. ., Previous studies [9, 25–27] have shown that shortening of PT and APTT can directly promote thrombosis in patients with malignant tumors, because circulating tumor cells can survive in single cell and can metastasize distantly. Fbg in tumors micrometastasis also plays an important role. It can provide necessary materials and locations for tumor cell micrometastasis, while avoiding tumor cells from being attacked by immune cells; D-D, as the final product of fibrinogen hydrolysis, is used in the differential diagnosis of breast cancer. In our study, it was correlated with clinicopathological characteristics, which are consistent with the results of this study. When analyzing the TNM staging of breast cancer patients in the postmenopausal and premenopause groups, it was found that in the T-stage of the premenopause patients, the Fbg level was higher in the T2-T3 stage than in the Tis-T1 stage in the premenopause group, while this did not occur in the postmenopausal group. In the postmenopausal patient group, PT levels are higher in Tis-T1 patients than in T2-T3 patients, and AT-III, PC, α2-AP, and FDP levels are higher in T2-T3 patients than Tis-T1 patients. The level of D-D was higher than that of Tis-T1 patients in T2-T3 stage patients in the premenopausal group or the postmenopausal group. In the N stage, Fbg levels in the premenopausal group are higher in the N1-N3 stage patients than in the N0 stage patients, but no change was observed in the postmenopausal patients; AT-III and α2-AP levels are in the premenopausal group and the postmenopausal group N1-N3 stage patients are higher than N0 stage patients. Studies have shown that coagulation/fibrinolysis index levels are irrelevant to the size and metastasis of tumors in breast cancer patients, based on different hormone levels in the patients [28, 29]. The changes in the hormone levels in the patients may cause or exacerbate the abnormality of the coagulation/fibrinolysis system indicators in patients, thereby further inducing and promoting the occurrence, development and metastasis of breast cancer.
The PT in the triple-negative patient group was significantly higher than the Luminal A + B group and the HER-2 overexpression group, while the Fbg in the HER-2 overexpression group was higher than that of the LuminalA + B group and the triple-negative breast Group, consistent with the research results reported in the existing literature [30, 31],indicating that HCY、PT 、Fbg、D-D indicators are closely related to the molecular typing of breast cancer, and can better predict the occurrence, development, and metastasis risk and prognosis of breast cancer.