Development and validation of nomograms for predicting survival outcomes in patients with T1-2N1 breast cancer to identify those who could not benefit from postmastectomy radiotherapy.

Purpose: In this study, we aimed to develop and validate nomograms for predicting the survival outcomes in patients with T1-2N1 breast cancer to identify the patients who could not benefit from postmastectomy radiotherapy (PMRT). Methods: Data from 10191 patients with T1-2N1 breast cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Of them, 6542 patients who had not received PMRT formed the training set. Concurrently, we retrospectively enrolled 419 patients from the Affiliated Hospital of North Sichuan Medical College (NSMC), and 286 patients who did not undergo PMRT formed the external validation set. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were used for selecting prognostic factors in the training set. Using the selected factors, two prognostic nomograms were constructed. The nomograms' performance was assessed using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and risk subgroup classification. The stabilized inverse probability of treatment weights (IPTWs) was used to balance the baseline characteristics of the different risk groups. Finally, the survival outcomes and effectiveness of PMRT after IPTW adjustment were evaluated using adjusted Kaplan-Meier curves and Cox regression models. Results: The 8-year overall survival (OS) and breast cancer-specific survival (BCSS) rates for the SEER cohort were 84.3% and 90.1%, with a median follow-up time of 76 months, while those for the NSMC cohort were 84.1% and 86.9%, with a median follow-up time of 73 months. Moreover, significant differences were observed in the survival curves for the different risk subgroups (P < 0.001) in both SEER and NSMC cohorts. The subgroup analysis after adjustment by IPTW revealed that PMRT was significantly associated with improved OS and BCSS in the intermediate- (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.59-0.88, P=0.001; HR = 0.77, 95% CI: 0.62-0.95, P = 0.015) and high- (HR=0.66, 95% CI: 0.52-0.83, P<0.001; HR=0.74, 95% CI: 0.56-0.99, P=0.039) risk groups. However, PMRT had no significant effects on patients in the low-risk groups. Conclusion: According to the prognostic nomogram, we performed risk subgroup classification and found that patients in the low-risk group did not benefit from PMRT.

Single progesterone receptor-positive phenotype has the similar clinicopathological features and outcome as triple-negative subtype in metastatic breast cancer.

Objective: The same clinicopathological features and prognosis have been reported between single progesterone receptor-positive (sPR-positive) and triple-negative phenotype in early-stage breast cancer, but such similarity has not been studied in metastatic breast cancer (MBC). Therefore, the purpose of this study was to estimate the difference between sPR-positive phenotype and other phenotypes in MBC. Methods: Patients with HER-2-negative MBC were selected from the Surveillance, Epidemiology and End Results database. Pearson's χ2 test was used to compare the difference of clinicopathologic factors between sPR-positive phenotype and other phenotypes. Univariate and multivariate analyses were performed to evaluate the effects of hormone receptor (HoR) phenotypes and other clinicopathologic factors on the cancer-specific survival (CSS) and overall survival (OS). Results: Overall, 10877 patients including 7060 patients (64.9%) with double HoR-positive (dHoR-positive), 1533 patients (14.1%) with single estrogen receptor-positive (sER-positive), 126 patients (1.2%) with sPR-positive and 2158 patients (19.8%) with double HoR-negative (dHoR-negative) were analyzed. The patients with sPR-positive or dHoR-negative were more likely to be younger, higher grade and tumor stage, visceral and brain metastasis than ER-positive phenotypes (P<0.001). MBC with sPR-positive had the similar CSS (HR: 1.135, 95%CI: 0.909-1.417, P=2.623) and OS (HR: 1.141, 95%CI: 0.921-1.413, P=0.229) as dHoR-negative, but worse outcome than ER-positive phenotypes. Chemotherapy significantly improved the survival for MBC, especially for sPR-positive MBC (CSS, HR: 0.39, 95%CI: 0.213-0.714, P=0.002; OS, HR: 0.366, 95%CI: 0.203-0.662, P=0.001). Conclusions: Patients with sPR-positive and triple-negative have similar biological behavior and prognosis in MBC. Chemotherapy may be a preferred recommendation for MBC with sPR-positive.

Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications

To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization.MethodsImmunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice.ResultsThe clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. (AU)

Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications.

OBJECTIVE: To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization. METHODS: Immunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice. RESULTS: The clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. The CCK-8 assay showed that the proliferation rate of MDA-MB-231 cells increased (P < 0.05) after shifting the subcellular localization of ANXA2 from the cell membrane to the cytoplasm. Transwell invasion assay and Transwell migration assay showed that the invasion and migration ability of MDA-MB-231 cells increased significantly after the subcellular localization of ANXA2 was transferred from the cell membrane to the cytoplasm (P < 0.05). The animal experiments showed that high-density breast cancer cells could promote the growth of subcutaneous tumors in nude mice relative to low-density breast cancer cells. CONCLUSION: Cell density can regulate the subcellular localization of ANXA2, and changes in the subcellular localization of ANXA2 are accompanied by the changes in the biological behavior of breast cancer.

Correlation Analysis of Breast and Thyroid Nodules: A Cross-Sectional Study.

OBJECTIVE: Based on physical examination, to explore the relationship between breast mass (BM) and thyroid nodule (TN) prevalence, and to further explore other related factors that affect the occurrence of BM and TN. METHODS: From January 1, 2018, to January 1, 2021, 12,538 female subjects received breast and thyroid ultrasound examinations at the same time in the health examination center of the Affiliated Hospital of North Sichuan Medical College. Univariate analysis and multivariate logistic analysis were used to screen the relevant factors affecting TN and BM, and propensity score matching was used to further verify the results of the relationship between breast and thyroid. RESULTS: A total of 4975 (39.7%) of the included subjects have BM and a total of 6315 (50.4%) have TN,2557 (20.4%) had both BM and TN. The logistic regression results show that patients with TN are more likely to suffer from BM [OR = 1.185, 95% CI (1.099-1.278), p<0.0001]. In addition, age, free T4, HDL, height, BMI, systolic blood pressure, diastolic blood pressure, and albumin are independent factors affecting the occurrence of BM; patients with BM are more likely to have TN [OR = 1.180, 95% CI (1.094-1.272), p<0.0001], and age, free T3, free T4, AST, ALT, albumin, height, and BMI are independent influencing factors on the occurrence of TN. The result of propensity score matching confirmed the relationship between BM and TN. CONCLUSION: There is a bidirectional pathogenic relationship between BM and TN, women with BM are at increased risk of TN, and women with TN are more likely to have BM. Thyroid hormone is not only related to the occurrence of TN but also affects the occurrence of BM.