Current scenario of chalcone hybrids with antibreast cancer therapeutic applications.

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationships as well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

Development and validation of a prognostic nomogram for breast cancer patients who underwent chemoradiotherapy and surgery: a retrospective cohort study based on the SEER database and two Chinese cohorts.

There is no strong evidence indicating the optimal treatment for breast cancer (BC) and no specific prognostic model. The aim of this study was to establish nomograms to predict the overall survival (OS) of BC patients receiving chemoradiotherapy and surgery, thereby quantifying survival benefits and improving patient management. A total of 1877 patients with primary nonmetastatic BC who received chemoradiotherapy and surgery from 2010 to 2019 were identified from the Surveillance, Epidemiology and End Results (SEER) database as the training cohort, 804 as the internal validation cohort, and 796 patients from the First Affiliated Hospital of Zhengzhou University (n=324) and Jiaxing Maternal and Child Health Hospital (n=472) as the external validation cohort. Least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analyses were performed in the training cohort to determine independent prognostic factors for BC, and a nomogram was constructed to predict 3-year, 5-year, and 8-year OS. The final model incorporated 7 factors that significantly affect OS: race, location, positive regional nodes, T stage, N stage, subtype, and grade. The calibration curves showed good consistency between the predicted survival and actual outcomes. Time-dependent receiver operating characteristic (ROC) curves and the time-dependent area under the curve (AUC) confirmed that the accuracy and clinical usefulness of the constructed nomograms were favorable. Decision curve analysis (DCA) and net reclassification improvement (NRI) also demonstrated that this nomogram was more suitable for clinical use than the 7th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system and the previous prediction model. In the training cohort and the internal validation cohort, the concordance indices (C-index) of the nomogram for predicting OS (0.723 and 0.649, respectively) were greater than those of the 7th AJCC TNM staging system and the previous prediction model. In addition, based on Kaplan-Meier (K-M) survival curves, the survival differences among different risk stratifications were statistically significant, indicating that our risk model was accurate. In this study, we determined independent prognostic factors for OS in patients with primary nonmetastatic BC treated with chemoradiotherapy and surgery. A new and accurate nomogram for predicting 3-, 5-, and 8-year OS in this patient population was developed and validated for potential clinical applicability.

Complication Differences Between the Tumescent and Non-Tumescent Dissection Techniques for Mastectomy: A Meta-Analysis.

PURPOSE: We conducted a systematic literature search and pooled data from studies to compare the incidence of complications between the tumescent and non-tumescent techniques for mastectomy. METHODS: We searched PubMed, Embase, BioMed Central, Ovid, and CENTRAL databases for studies comparing the two mastectomy techniques up to November 1st, 2020. We used a random-effects model to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Nine studies were included with one randomized controlled trial (RCT). Meta-analysis indicated no statistically significant difference in the incidence of total skin necrosis (OR 1.18 95% CI 0.71, 1.98 I2 = 82% p=0.52), major skin necrosis (OR 1.58 95% CI 0.69, 3.62 I2 = 71% p=0.28), minor skin necrosis (OR 1.11 95% CI 0.43, 2.85 I2 = 72% p=0.83), hematoma (OR 1.19 95% CI 0.80, 1.79 I2 = 4% p=0.39), and infections (OR 0.87 95% CI 0.54, 1.40 I2 = 54% p=0.56) between tumescent and non-tumescent groups. Analysis of studies using immediate alloplastic reconstruction revealed no statistically significant difference in the incidence of explantation between the two groups (OR 0.78 95% CI 0.46, 1.34 I2 = 62% p=0.37). Multivariable-adjusted ORs on total skin necrosis were available from three studies. Pooled analysis indicated no statistically significant difference between tumescent and non-tumescent groups (OR 1.72 95% CI 0.72, 4.13 I2 = 87% p=0.23). CONCLUSION: Low-quality evidence derived mostly from non-randomized studies is indicative of no difference in the incidence of skin necrosis, hematoma, seroma, infection, and explantation between the tumescent and non-tumescent techniques of mastectomy. There is a need for high-quality RCTs to further strengthen the evidence.

Compliance with multidisciplinary team recommendations and disease outcomes in early breast cancer patients: An analysis of 4501 consecutive patients.

BACKGROUND: Multidisciplinary team (MDT) discussions are widely held to facilitate the diagnosis and treatment of breast cancer, but patient compliance with the MDT recommendations and the impact of compliance on disease outcome are uncertain. METHODS: We conducted a retrospective review of data from a prospective database of breast cancer patients treated at Shanghai Ruijin Hospital between April 2013 and August 2018. MDT discussions were held for all patients before they started adjuvant therapy. The patients were classified into compliant and non-compliant groups according to whether they received the MDT-recommended regimens. We also analyzed which clinicopathological factors were associated with compliance and prognosis. RESULTS: Of 4501 breast cancer patients, 3681 (81.8%) and 820 (18.2%) were included in the compliant and non-compliant groups, respectively. Age >70 years (P < 0.001), invasive ductal carcinoma (P < 0.001), and histological grade III (P = 0.011) were independently associated with higher risk of non-compliance, whereas Ki-67 labeling index ≥14% and history of benign breast disease were independently associated with compliance. Disease-free survival (hazard ratio [HR] 1.813, 95% confidence interval [CI] 1.367-2.405, P < 0.001) and overall survival (HR 2.478, 95% CI 1.431-4.291, P < 0.001) were worse in the non-compliant group. CONCLUSIONS: Several clinicopathological factors were associated with non-compliance with MDT recommendations for early breast cancer patients. Non-compliance was associated with worse disease outcome.

Prolonged Time to Adjuvant Chemotherapy Initiation Was Associated with Worse Disease Outcome in Triple Negative Breast Cancer Patients.

The optimal time to adjuvant chemotherapy (TTC) for breast cancer (BC) patients remains uncertain. Herein, we aim to evaluate the association between TTC and prognosis among different subtypes in modern era of adjuvant chemotherapy. BC patients receiving operation and adjuvant chemotherapy between January 2009 and December 2015 were included. Enrolled patients were categorized into TTC ≤4 weeks and >4 weeks groups. Relapse-free survival (RFS) and overall survival (OS) were compared according to TTC and analyzed among different BC molecular subtypes. A total of 2611 patients were included. Elder age (P = 0.005), more comorbidities (P <0.001), breast-conserving surgery (P = 0.001), non-invasive ductal carcinoma (P = 0.012), and HER2-positivity (P <0.001) were associated with prolonged TTC. Among whole BC population, no significant difference was observed between two TTC groups in terms of RFS (P = 0.225) or OS (P = 0.355). However, for triple negative (TNBC) patients, TTC >4 weeks was independently related with worse RFS (5-year RFS 81.9% vs 89.3%; HR, 1.89; 95% CI, 1.09 to 3.27; P = 0.024) and OS (5-year OS 84.0% vs 94.0%; HR, 2.49; 95% CI, 1.30 to 4.76; P = 0.006) compared with those TTC ≤4 weeks. Prolonged TTC >4 weeks after BC surgery was not associated with worse survival outcomes in the whole BC patients. However, TTC >4 weeks may increase risk of relapse or death in TNBC patients, which deserves further clinical evaluation.

[Efficacy of adjuvant endocrine therapy in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy].

Objective: To evaluate the efficacy of adjuvant endocrine therapy (AET) in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy (NAC). Methods: One hundred and six patients who presented with hormone receptor (HR)-positive breast cancer at diagnosis and turned to HR-negative after NAC during December 2000 and December 2013 in Jiaxing Maternity and Child Health Care Hospital were retrospectively identified. Kaplan-Meier analysis and log-rank test were used for univariate analyses of factors related to disease free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model in patients with DFS and OS. Results: All the patients were categorized into two groups on the basis of the administration of AET:61 AET-administered patients (57.5%) and 45 AET-naïve patients (42.5%). After a median follow-up of 68 months (range 14-103 months), human epidermal growth factor receptor 2 (HER-2) status, initial clinical stage, pathological axillary lymph node status and the use of AET were identified as the variables affecting DFS and OS (all P<0.05). Patients treated with AET had a significantly improved 5-year DFS rate when compared with that without AET (77.1% vs 53.5%,P<0.05). The 5-year OS of AET-administered patients was also better than that of AET-naïve patients (80.9% vs 71.0%,P<0.05). Cox regression analysis showed that AET-administered or not was the independent predictor for 5-year DFS (HR=2.096, 95% CI:1.081-4.065, P<0.05). Conclusion: Patients with HR altered from positive to negative after NAC may still gain benefit from AET.