Serum sPD-1 and sPD-L1 as Biomarkers for Evaluating the Efficacy of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is widely administered in the primary treatment of triple-negative breast cancer (TNBC). However, serum biomarkers for evaluating or monitoring the curative efficacy of NAC have not been established. Accumulating data have shown that soluble programmed death 1 (sPD-1) and its ligand (sPD-L1) might be potential biomarkers for evaluating the curative efficacy of chemotherapy and patient prognosis in several cancers but not yet in breast cancer. PATIENTS AND METHODS: Blood specimens were obtained from 66 TNBC patients who received NAC and 59 healthy women. The serum concentrations of sPD-1 and sPD-L1 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared to healthy women, the serum concentration of sPD-1 was significantly elevated in TNBC patients before NAC (549.3 ± 58.76 pg/mL vs. 379.2 ± 17.30 pg/mL, P = .007), but there was only an increase tendency for sPD-L1 (227.7 ± 23.99 pg/mL vs. 195.0 ± 8.49 pg/mL, P = .22). The serum levels of sPD-1 and sPD-L1 before NAC in TNBC patients increased with tumor stage (P = .038 and .030, respectively). Patients who experienced complete or partial remission after NAC had significantly decreased serum levels of sPD-1 and sPD-L1 compared to patients with a poor response to NAC (P = .019 and .021, respectively). CONCLUSION: Serum levels of sPD-1 and sPD-L1 could be used as noninvasive biomarkers for evaluating the malignancy of TNBC before NAC and for predicting the NAC response in TNBC patients.

Association between WT1 polymorphisms and susceptibility to breast cancer: results from a case-control study in a southwestern Chinese population.

Wilms' tumor gene 1 (WT1) single nucleotide polymorphism (SNP), rs16754, has been considered as an independent prognostic factor in patients with acute myeloid leukemia and renal cell carcinoma. However, its biological role in breast cancer has not been reported. To test whether WT1 SNPs can be used as a molecular marker in order to improve the risk stratification of breast cancer, we performed a case-control study including 709 female sporadic breast cancer patients and 749 female healthy control subjects in the Southeast China. Five WT1 SNPs (rs16754, rs3930513, rs5030141, rs5030317, rs5030320) were selected and determined by polymerase chain reaction-ligase detection reaction to assess their associations with breast cancer risk. Results showed the distributions of the alleles of these WT1 SNPs were consistent with data from Chinese population as suggested by the International HapMap Project. Individuals with the minor alleles of rs16754, rs5030317 and rs5030320 showed a significant decrease of breast cancer risk in codominant model (OR = 0.6370, 95% CI: 0.4260-0.9520 for rs16754; OR = 0.5940, 95% CI: 0.3890-0.9070 for rs5030317; OR = 0.5870, 95% CI: 0.3850-0.8960 for 5030320, respectively) and recessive model. Stratified analyses showed the protective effects were more evident in the subjects with age ≤ 50 years or in pre-menopausal status. To explore the potential mechanism, we conducted bioinformatics genotype-phenotype correlation analysis, and found that the mRNA expression level for homozygous rare allele of WT1 gene was lower than that in wild-type and heterozygous group (P = 0.0021) in Chinese population. In summary, our findings indicated that minor alleles of rs16754, rs5030317 and rs5030320 are associated with reduced risk of breast cancer, suggesting that WT1 SNPs may be a potential biomarker of individualized prediction of susceptibility to breast cancer. However, large prospective and molecular epidemiology studies are needed to verify this correlation and clarify its underlying mechanisms.

Efficacy of Psychological Interventions for Patients with Breast Hyperplasia.

To explore the efficacy of psychological interventions (PI) in patients with breast hyperplasia (BH). In total 120 BH patients who were treated in the Third Affiliated Hospital of the Third Military Medical University were randomly divided into PI group (n = 40; treated with oral XiaoYao Pill and psychological interventions), anti-anxiety/depression medication (AADM) group (n = 40; treated with oral XiaoYao Pill and paroxetine), and control group (n = 40; treated with oral XiaoYao Pill) and the treatment lasted for 1 year. Before the treatment and 4, 8, and 12 months after the initiation of treatment, the changes in the psychological indicators were measured using Toronto Alexithymia Scale (TAS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Ways of Coping Questionnaire (WCQ), as well as the physiological indicators including estradiol, prolactin, and progesterone were determined. The overall response rates were evaluated at the end of the treatment, and the relapse rates were calculated during the 1-year follow-up. The HAMD and HAMA scores were declined in all three groups. The scores of TAS and WCQ negative coping subscales showed a declining trend after treatment for the AADM and PI groups. Compared to the control and PI groups, the HAMA and HAMD scores were significantly lower in the AADM group 4, 8, and 12 months after the initiation of treatment (P < 0.05). The scores of TAS and WCQ negative coping subscales were significantly lower in AADM group but were significantly higher than those in PI group and lower than the control group 4, 8, and 12 months after the initiation of treatment (P < 0.05). The HAMA and HAMD scores were significantly lower in PI group than in control group 4, 8, and 12 months after the initiation of treatment (P < 0.05). After the initiation of treatment, the estradiol and prolactin levels decreased while the progesterone levels increased in all three groups. Compared with the control group and AADM group, the PI group had significantly higher estradiol and prolactin levels and higher progesterone levels 4, 8, and 12 months after the initiation of treatment (P < 0.05). Compared with the control group, the AADM group had significantly lower levels of estradiol and prolactin and higher progesterone levels 4, 8, and 12 months after the initiation of treatment (P < 0.05). The overall response rate was not significantly different for both PI group and AADM group (P > 0.05), while the relapse rate was significantly lower in the PI group than the control and AADM groups (P < 0.05). However, the relapse rate did not significantly differ between the control group and AADM group (P > 0.05). PI can effectively improve the psychological status of BH patients and restore the disordered endocrine system. The efficacy lasts for long and the relapse rate is lower. Therefore, it could be an effective method for treating BH.

High Wilms' tumor 1 mRNA expression correlates with basal-like and ERBB2 molecular subtypes and poor prognosis of breast cancer.

The role of Wilms' tumor 1 (WT1) in breast cancer and the relationship between WT1 expression and clinicopathological factors, molecular subtypes and prognosis of breast cancer patients have not been clarified to date. We used publicly available microarray datasets of 266 early breast cancer patients to perform bioinformatics analysis on the relationship between WT1 mRNA expression and breast cancer. Results showed that WT1 mRNA expression was correlated with higher histological grades, ER-negative and basal-like and ERBB2 molecular subtypes in breast cancer. With regard to disease-free survival analysis, the WT1 high expression group showed worse prognosis than the low expression group in univariate analysis, and WT1 was demonstrated to be an independent prognostic indicator in multivariate analysis. This study confirms an oncogenic role of WT1 and demonstrates a possible relation between WT1 and progression of breast cancer.