Predictive nomogram based on serum tumor markers and clinicopathological features for stratifying lymph node metastasis in breast cancer.

BACKGROUND: This study was aimed to establish the nomogram to predict patients' axillary node status by using patients' clinicopathological and tumor characteristic factors. METHODS: A total of 705 patients with breast cancer were enrolled in this study. All patients were randomly divided into a training group and a validation group. Univariate and multivariate ordered logistic regression were used to determine the predictive ability of each variable. A nomogram was performed based on the factors selected from logistic regression results. Receiver operating characteristic curve (ROC) analysis, calibration plots and decision curve analysis (DCA) were used to evaluate the discriminative ability and accuracy of the models. RESULTS: Logistic regression analysis demonstrated that CEA, CA125, CA153, tumor size, vascular-invasion, calcification, and tumor grade were independent prognostic factors for positive ALNs. Integrating all the predictive factors, a nomogram was successfully developed and validated. The C-indexes of the nomogram for prediction of no ALN metastasis, positive ALN, and four and more ALN metastasis were 0.826, 0.706, and 0.855 in training group and 0.836, 0.731, and 0.897 in validation group. Furthermore, calibration plots and DCA demonstrated a satisfactory performance of our nomogram. CONCLUSION: We successfully construct and validate the nomogram to predict patients' axillary node status by using patients' clinicopathological and tumor characteristic factors.

A retrospective clinical study of patients with pregnancy-associated breast cancer among multiple centers in China (CSBrS-008).

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a special type of breast cancer that occurs during pregnancy and within 1 year after childbirth. With the rapid social development and the adjustment of reproductive policies in China, the average age of females at first childbirth is increasing, which is expected to lead to an increase in the incidence of PABC. This study aimed to accumulate clinical experience and to investigate and summarize the prevalence, diagnosis, and treatment of PABC based on large multicenter samples in China. METHODS: According to the Chinese Society of Breast Surgery, a total of 164 patients with PABC in 27 hospitals from January 2016 to December 2018 were identified. The pregnancy status, clinicopathological features, comprehensive treatment methods, and outcomes were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method. RESULTS: A total of 164 patients of PABC accounted for 0.30% of the total number of cases in the same period; of which, 83 patients were diagnosed during pregnancy and 81 patients during lactation. The median age of PABC was 33 years (24-47 years). Stage I patients accounted for 9.1% (15/164), stage II 54.9% (90/164), stage III 24.4% (40/164), and stage IV 2.4% (4/164). About 9.1% (15/164) of patients were luminal A. Luminal B patients accounted the most (43.3% [71/164]). About 15.2% (25/164) of patients were human epidermal growth factor receptor 2 (Her-2) overexpression and 18.9% (31/164) of patients were triple-negative breast cancer. For pregnancy breast cancer, 36.1% (30/83) of patients received direct surgery and 20.5% (17/83) received chemotherapy during pregnancy. About 31.3% (26/83) chose abortion or induction of labor. The median follow-up time was 36 months (3-59 months); 11.0% (18/164) patients had local recurrence or distant metastasis and 3.0% (5/164) died. CONCLUSIONS: It is safe and feasible to standardize surgery and chemotherapy for PABC.

Tumor infiltrating neutrophil might play a major role in predicting the clinical outcome of breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: This study was aimed to explore the predictive ability of tumor infiltrating neutrophil (TIN) in patients with breast cancer treated with neoadjuvant chemotherapy (NACT). Furthermore, the significance of TIN's dynamic change before and after NACT was investigated. METHODS: Between January 2004 and December 2017, a total of 133 patients with breast cancer who underwent NACT before surgery were enrolled in this retrospective cohort. Eighty-nine of them were able to get the core needle biopsy (CNB) samples and all the pathological samples after surgery were available. TIN was detected by immunohistochemical staining of CD66b. The optimal cut-off value was determined via receiver operating characteristic (ROC) curve analysis. The association of clinicopathologic characteristics and chemotherapy efficiency was analyzed using X2 test or Fisher's exact test or t-test as appropriate, and the prognostic significances were assessed by univariate and multivariate analyses. RESULTS: Patients with higher TIN after NACT were confirmed to be significantly associated with worse prognosis (P = 0.002). After stratifying patients into two groups, high difference group was prone to have better chemotherapy efficiency (P < 0.001) and clinical outcome in both univariate (P = 0.002) and multivariate analyses (P = 0.003). CONCLUSIONS: In this study, higher TIN after NACT was confirmed to be associated with breast cancer patients' worse chemotherapy efficiency and shorter disease-free survival (DFS). Furthermore, the TIN's dynamic change before and after NACT was firstly proved to be a more accurate predictive marker compared with TIN after NACT.

The functional role of the EZH2 gene in controlling breast cancer stem cells.

PURPOSE: Breast cancer is caused by rare populations of self-renewing cancer stem cells that might also play a role in tumor relapse. Genes that regulate cancer stem cells are, therefore, of great interest in controlling cancer. EZH2 gene expression is reported to be elevated during breast cancer progression and it plays a role in expanding breast stem cell populations. In the current study, we analyzed the correlation between the silencing effect of EZH2 and breast cancer stem cell expansion. METHODS: We used CD44+/CD24-/low cells to develop initial-, moderate-, and advanced-stage breast cancers in female NOD/SCID mice. Immunohistochemistry and western blotting were used to study the expression of aldehyde dehydrogenase 1 (ALDH1) and EZH2 in different stages of breast cancer. RESULTS: Histology showed that as tumors progressed, the pathological condition changed exhibiting enlarged nuclei, higher cell proliferation, and more invasive cells. In EZH2-silenced mice histopathology also showed enlarged cell nucleus, lesion formation and cell aggregation. Immunohistochemistry and western blotting analyses of EZH2 and ALDH1 demonstrated elevated expression as tumors progressed to the next level. Interestingly, the expression of ALDH1 in EZH2-silenced breast cancer tissue showed prolonged overexpression. CONCLUSIONS: We conclude that the normal expression of EZH2 in cancer tissue controls cancer stem cell expansion, because it is highly elevated in EZH2-silencing cancer tissue.

Expression of SOX11 and HER2 and their association with recurrent breast cancer.

BACKGROUND: Recurrent breast cancer occurs as a result of divergent gene expression in response to therapeutic intervention. A recent report showed that SOX11, an embryogenic mammary transcription factor, is overexpressed in breast cancer. HER2 is also dysregulated in breast cancer stem cells; however, the relative expression of these two genes in recurrent breast cancer has not been investigated. METHODS: Mouse models of mild and advanced stage recurrent breast cancer were developed via implantation of different doses of 4T1 Luc2GFP cells. The cellular morphology of normal and recurrent breast cancer tissues was analyzed using standard histological methods. SOX11, HER2, and ALDH1 expression levels were analyzed via immunohistochemistry and western blotting. RESULTS: Histological analyses revealed that treatment with doxorubicin limited mild recurrent cancer but was ineffective against advanced stage recurrent cancers, as evidenced by increased cell proliferation. SOX11 was consistently overexpressed in mild and advanced stage breast cancers treated with doxorubicin, relative to HER2, which exhibited reduced expression in response to doxorubicin treatment in both mild and advanced stage recurrent breast cancer. In advanced stage recurrent breast cancer, SOX11 expression was more readily observed across the cell surface and was correlated with the overexpression of the breast cancer stem cell marker ALDH1. CONCLUSIONS: These results show that SOX11 expression was directly associated with breast cancer stem cell populations. In contrast, HER2 expression was strongly associated with drug treatment effects, but was not correlated with breast cancer stem cell survival in recurrent breast cancer.

Neutrophil to lymphocyte ratio is a prognostic factor for disease free survival in patients with breast cancer underwent curative resection.

The aim of this study was to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) in patients with breast cancer after curative resection. Furthermore, we aimed to confirm the prognostic significance of NLR in early stage and different molecular types of breast cancer, as well as patients treated with neoadjuvant chemotherapy (NACT).A total of 2458 patients between January 2002 and December 2014 from 2 independent cohorts were analyzed retrospectively. The optimal cut-off value of NLR for recurrence was determined via receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to assess the relationship between NLR and disease-free survival (DFS).Both univariate and multivariate analysis showed that patients with high NLR were more inclined to suffer postoperative recurrence in 2 independent cohorts. NLR was identified as independent prognostic factor for DFS of early stage breast cancer (P < .05), different types of breast cancer (P < .05) and patients treated with NACT (P < .05).Our data suggest NLR is independent prognostic factor for breast cancer patients. In addition, the prognostic value of NLR was further confirmed in early stage and different molecular types of breast cancer as well as patients treated with NACT.

Effectiveness of hemostasis with Foley catheter after vacuum-assisted breast biopsy.

BACKGROUND: Interventional bleeding and post-interventional hematoma are the most common complications following vacuum-assisted breast biopsy (VABB). The aim of the current study was to evaluate the effectiveness of Foley catheter-induced hemostasis in VABB. METHODS: A randomized prospective controlled trial was conducted using a total of 437 consecutive 8-gauge ultrasound-guided VABB procedures that were performed in 282 patients from June 2012 to October 2013. In each procedure, hemostasis was induced with either a Foley catheter or with external compression. Bleeding during intervention, hematoma post-intervention and the time of procedure were recorded. Statistical analysis included a Chi-Square test and an independent-samples t-test, and P value <0.05 was considered to be significant. RESULTS: Significantly less bleeding and post-interventional hematoma resulted when hemostasis was induced using a Foley catheter vs. compression (7.6% vs. 17.4%, P=0.002; 8.9% vs. 27.9%, P<0.001). The mean time of breast biopsy was significantly less when using a Foley catheter vs. compression (33.6 vs. 45.5 min, P<0.001). No post-procedural infectious was encountered. In stratification analysis, there were no significantly different bleeding rates between the Foley catheter and compression methods in cases of single lesions (6.7% vs. 14.1%, P=0.346). In cases of multiple lesions, the Foley catheter method produced less bleeding/hematoma than compression (10.4% vs. 47.4%, P=0.018; 16.7% vs. 52.6%, P=0.020). Whether using a Foley catheter or compression to induce hemostasis, no significant difference was found in the rate of bleeding or hematoma when lesions <15 mm were removed (3.8% vs. 6.1%, P=0.531; 6.1% vs. 11.4%, P=0.340). When lesions ≥15 mm were excised, the rates of interventional bleeding and post-interventional hematoma were significantly lower in the Foley catheter study group than the compression control group (12.5% vs. 32.2%, P=0.034; 12.5% vs. 49.4%, P<0.001). There was significantly less bleeding (P=0.004) and hematoma (P<0.001) in the upper external quadrant when using a Foley catheter compared with compression (4.5% vs. 15.7%, P=0.004; 9.8% vs. 40.2%, P<0.001), but no significant differences for other quadrants. CONCLUSIONS: Inducing hemostasis with a Foley catheter after VABB is a very effective and safe alternative to hemostasis with compression.