Circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers combined with clinicopathological risk has potential to better predict recurrence in stage III breast cancer treated with neoadjuvant chemotherapy: a pilot study.

BACKGROUND: The potential value of detecting epithelial-mesenchymal transition (EMT) CTCs in early breast cancer, especially during the neoadjuvant therapy period, requires further investigation. We analyzed dynamic CTC phenotype status, to improve recurrence risk stratification for patients with stage III breast cancers. METHODS: We enrolled 45 patients with stage III breast cancers from 2 clinical trials undergoing neoadjuvant chemotherapy and utilized the CanPatrol CTC enrichment technique pre- and post-chemotherapy to identify CTC phenotypes, including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs, in peripheral blood samples. Kaplan-Meier analyses were conducted to explore the prognostic value of dynamic change of CTC count and the proportion of CTCs with different phenotypes. Then, redefine the risk stratification based on CTC status and clinicopathological risk in combination. RESULTS: Increased proportion of M + CTCs was a high-risk CTC status that was associated with decreased DFS (HR, 3.584; 95% CI, 1.057-12.15). In a combined analysis with clinicopathological risk, patients with high-risk tumors had an elevated risk of recurrence compared to patients with low-risk tumors (HR, 4.482; 95% CI, 1.246-16.12). The recurrence risk could be effectively stratified by newly defined risk stratification criteria, with 5-year DFS of 100.0%, 77.3%, and 50.0%, respectively, for low-risk, mid-risk, and high-risk patients (P = 0.0077). Finally, in the ROC analysis, the redefined risk stratification demonstrated higher predictive significance with an AUC of 0.7727, compared to CTC status alone (AUC of 0.6751) or clinicopathological risk alone (AUC of 0.6858). CONCLUSION: The proportion of M + CTCs increased after neoadjuvant chemotherapy indicating a higher risk of tumor recurrence. Combining CTC status with clinicopathological risk has potential to redefine the risk stratification of stage III breast cancers and provide improved predictions of relapse.

Adjuvant chemotherapy and survival outcomes in older women with HR+/HER2- breast cancer: a propensity score-matched retrospective cohort study using the SEER database.

OBJECTIVES: This study aimed to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in older women with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). DESIGN: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database, which contains publicly available information from US cancer registries. SETTING AND PARTICIPANTS: The study included 45 762 older patients with BC aged over 65 years diagnosed between 2010 and 2015. METHODS: Patients were divided into two groups based on age: 65-79 years and ≥80 years. Propensity score matching (PSM) was employed to balance clinicopathological characteristics between patients who received ACT and those who did not. Data analysis used the χ2 test and Kaplan-Meier method, with a subgroup analysis conducted to identify potential beneficiaries of ACT. OUTCOME MEASURES: Overall survival (OS) and cancer-specific survival (CSS). RESULTS: Due to clinicopathological characteristic imbalances between patients with BC aged 65-79 years and those aged ≥80 years, PSM was used to categorise the population into two groups for analysis: the 65-79 years age group (n=38 128) and the ≥80 years age group (n=7634). Among patients aged 65-79 years, Kaplan-Meier analysis post-PSM indicated that ACT was effective in improving OS (p<0.05, HR=0.80, 95% CI 0.73 to 0.88), particularly in those with advanced disease stages, but did not show a significant benefit in CSS (p=0.09, HR=1.13, 95% CI 0.98 to 1.31). Conversely, for patients aged ≥80 years, ACT did not demonstrate any improvement in OS (p=0.79, HR=1.04, 95% CI 0.79 to 1.36) or CSS (p=0.09, HR=1.46, 95% CI 0.69 to 2.26) after matching. Subgroup analysis also revealed no positive impact on OS and CSS. CONCLUSIONS: Patients with HR+/HER2- BC ≥80 years of age may be considered exempt from ACT because no benefits were found in terms of OS and CSS.

Hsa_circ_0002496 promotes the growth, angiogenesis, and stemness of breast cancer cells via miR-433-3p/YWHAZ cascade.

BACKGROUND: Breast cancer (BC) has been studied more and more in modern medicine. Circ_0002496 has established a critical role in BC. MiR-433-3p can exert important activity in cancer. YWHAZ can participate in BC development, but the targeting relationship among the three variables and its influence on the related process of BC are not clear. METHODS: RT-qPCR was used to analyze circ_0002496, miR-433-3p, and YWHAZ expression. Immunoblotting was used to analyze YWHAZ, Bax, Bcl-2, and PI3K/AKT-related proteins. RNase R assay was used to verify the ring structure of circ_0002496. Cell phenotypes were tested by Cell Counting Kit 8, EdU, sphere formation, tube formation, and flow cytometry assays. RESULTS: Circ_0002496 was enhanced and MiR-433-3p was downregulated in BC, while the expression of YWHAZ was higher in BC. Circ_0002496 targeted miR-433-3p and miR-433-3p targeted YWHAZ in BC cells. Depletion of circ_0002496 influenced the BC process, but miR-433-3p inhibitor reversed the impact of si-circ_0002496 on the BC process. Re-expression of YWHAZ weakened the influence of miR-433-3p on the BC process. Depletion of circ_0002496 could astrict tumor growth in vivo. Moreover, the circ_0002496/miR-433-3p/YWHAZ axis mediated the activation of the PI3K/AKT signaling pathway. CONCLUSION: Circ_0002496 participated in the malignant procession of BC by miR-433-3p/YWHAZ regulation cascade.

Real­world data indicated that neoadjuvant chemotherapy alone was associated with a higher risk of tumor recurrence in high­risk breast cancer subgroup patients.

Numerous clinical trials have reported equal effects of tumor control between neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) in patients with breast cancer (BC). However, this conclusion has not been verified in practice. The present retrospective study evaluated if there were different risk profiles for NAC, AC and their combinative modes on disease-free survival (DFS) in patients with BC using real-world data. All women with primary unilateral Stage I-III BC and first recurrence in 2008-2018 at The Fourth Hospital of Hebei Medical University were retrospectively identified for enrollment. The four modes of chemotherapy administered for primary BC were classified as 'None', 'NAC only', 'NAC+AC' and 'AC only'. One multivariate Cox model was used to estimate the adjusted Hazard Ratio (HR) and P-value. Covariates included age, Easter Cooperative Oncology Group grade, T stage, N stage, pathology, grade, lymphovascular invasion (LVI), BC subtype, number of chemotherapy cycles and other therapies. Amongst 637 patients, who had a mean age of 48.2 years at BC diagnosis and 50.9 years at recurrence, the median DFS by the 'None' (n=27), 'NAC only' (n=47), 'NAC+AC' (n=118) and 'AC only' (n=445) modes were 31.4, 16.6, 22.6 and 28.4 months (P<0.001), respectively. Compared with the 'AC only', adjusted HR (P-value) of the 'None', 'NAC only' and 'NAC+AC' modes on tumor recurrence were 1.182 (0.551), 1.481 (0.037) and 1.102 (0.523), respectively. The adjusted HR of 'NAC only' vs. 'AC only' modes were 1.448 (P=0.157) for locoregional recurrence and 2.675 (P=0.003) for distant recurrence. Stratified analyses further indicated that the 'NAC only' mode was associated with a higher recurrence risk in T3-4, N2-3, LVI-positive, or HER2-negative subgroup patients. In conclusion, NAC alone was associated with a higher risk of tumor recurrence in high-risk BC subgroup patients in real-world data. Patient selection of chemotherapy mode was involved in practice but could not fully explain this finding. The 'inadequate' NAC was highly likely to have accounted for this observation.

A large single-center prospective study to investigate the factors influencing the choice of breast-conserving surgery versus mastectomy in Chinese women with early breast cancer.

BACKGROUND: Compared to mastectomy, breast-conserving surgery (BCS) provides the same survival rate and a higher quality of life for patients with early breast cancer (EBC). However, Chinese women with EBC are known to have a low BCS rate. A large prospective cohort study was conducted to investigate the factors influencing the choice of BCS in this population. METHODS: In 2017, all women with unilateral EBC and eligible for BCS at our institution were enrolled. Before surgery, the patient's trust in the surgeon and her perceived strength of the surgeon's recommendation of BCS were measured through an in-person interview and validated ad hoc questionnaire. Multivariate logistic regressions on BCS procedure vs. mastectomy were used to estimate the odds ratio (OR). RESULTS: One thousand one hundred thirty-six patients enrolled at analysis had an average age of 51.8 and tumor size of 2.4 cm. 19.9% of patients had BCS. The "strong" level of trust in the surgeon was significantly associated with BCS with an OR of 2.944 (p<0.001) when compared to the "average or under" trust. The "strong" and "moderate" strengths in surgeon recommendation for BCS were also found to be significantly associated with the BCS procedure with ORs of 12.376 (p <0.001) and 1.757 (p =0.040), respectively, compared to the "neutral or dissuaded" strength. CONCLUSIONS: Stronger trust in surgeons and BCS recommendation by surgeons are associated with a higher rate of BCS in Chinese women with EBC. Interventional trials are needed to confirm this finding.

Full Compliance of Adjuvant Endocrine Therapy Is Associated with Higher Disease-Free Survival in Hormone Receptor-Positive and HER2-Negative Chinese Breast Cancer Patients with First Tumor Recurrence.

PURPOSE: To characterize the compliance status of adjuvant endocrine therapy (aET) and its relationship with disease-free survival (DFS) in hormone receptor-positive (HR+) and HER2-negative (HER2-) in Chinese breast cancer (BC) patients with first tumor recurrence. METHODS: All women with primary unilateral stage I - III HR+HER2- BC and first tumor recurrence in 2008 - 2018 at our institution were identified. Full (vs. none/partial) compliance of aET was classified from records. Multivariate Cox regression estimated the hazard ratio (HR), its 95% confidence interval (CI), and p value. DFS. Covariates included age, T stage, N stage, pathology, tumor grade, LVI, chemotherapy, radiotherapy.      Results: A total 258 patients had average age 47.4 years at BC diagnosis and median DFS 31.7 months. Patients with ipsilateral (contralateral) region and organ recurrence were 47.7% (19.8%) and 71.9%. Compared to the patients with none/partial compliance of aET, the full compliance patients (54.3% ) had a higher DFS (median 35.0 vs. 25.2 months, p=0.009). Multivariate analysis showed that the full compliance of aET was associated with a lower HR 0.614 (95%CI 0.467 - 0.807, p<0.001) on recurrence. Early discontinuation (67.5%, 56/83) due to the drug side effects was the top reason for partial compliance of aET. CONCLUSIONS: Full compliance of aET was quite low in Chinese HR+HER2- BC patients. However, it was associated with a 38.6% lower risk of first tumor recurrence. To search for effective tools to improve the compliance of aET in this population should be stressed.

NRBP1 negatively regulates SALL4 to reduce the invasion and migration, promote apoptosis and increase the sensitivity to chemotherapy drugs of breast cancer cells.

The incidence of breast cancer (BC) ranks first among all kinds of female malignancies. Its invasion, migration, apoptosis and resistance to chemotherapeutic drugs are the focus of current research. Nuclear receptor binding protein 1 (NRBP1) and spalt-like transcription factor 4 (SALL4), which are observed to be abnormally expressed in BC, are investigated herein to identify their involvement in invasion, migration, apoptosis and chemotherapeutic drug sensitivity of BC and to elucidate the underlying mechanism. After NRBP1 was overexpressed by cell transfection, wound healing and Transwell experiments were used to detect the abilities of cell invasion and migration, and western blotting was used to detect the expression of MMP2 and MMP9. Cell viability and apoptosis were detected by Cell Counting Kit-8 assay, TUNEL staining and western blotting, in which Doxorubicin (DOX) and cis-platinum (Cis) were administrated after overexpression of NRBP1. Finally, after overexpression of NRBP1 and SALL4, the cell invasion, migration and apoptosis, and the sensitivity to DOX and Cis, were detected to explore the underlying mechanism. Overexpression of NRBP1 inhibited the invasion and migration, promoted the apoptosis, and enhanced the chemotherapeutic effect of chemotherapy drugs in BC cells. Overexpression of SALL4 in cells blocked the effects of NRBP1 overexpression on invasion, migration, apoptosis and DOX and Cis drug sensitivity of BC cells. In conclusion, NRBP1 negatively regulated SALL4 to reduce the invasion and migration capacities, promote apoptosis and increase the sensitivity to chemotherapeutic drugs of BC cells.

Regulatory Focus, Motivation, and Their Relationship With Creativity Among Adolescents.

Due to the close relationship among intrinsic/extrinsic motivation, regulatory focus, and creativity revealed by previous literature, intrinsic/extrinsic motivation may play a mediating role between regulatory focus and creativity. Therefore, the present study aimed to investigate the relationship between regulatory focus and creativity by combining intrinsic/extrinsic motivation. In this study, senior high school students (n = 418) completed the Regulatory Focus Questionnaire, the Working Preference Inventory, the Williams Creativity Assessment Packet, and the Kirton Adaption-Innovation Inventory. The correlation analysis showed that both promotion and prevention focus positively correlated with intrinsic motivation; intrinsic motivation and promotion focus positively correlated with creativity personality and innovative-adaptive cognitive style; and extrinsic motivation and prevention focus negatively correlated with innovative-adaptive cognitive style. Furthermore, a path model showed that promotion focus positively predicted creativity through the mediation of intrinsic motivation. In general, our study suggests that intrinsic motivation plays a mediating role between promotion focus and creativity. Our results complement those of previous studies and serve as inspiration for the cultivation of creativity in classroom or enterprise settings.