Rate Of Breast Cancer Patients Research Articles

Neoadjuvant chemotherapy response, disease-free survival, and overall survival of breast cancer in a single institution

BackgroundBreast cancer is the most common malignancy among women worldwide. Previous studies have shown factors influencing breast cancer patients' survival, including histopathological grading, stage, histopathological type, hormone receptors, and the number of mitotic images. This study aimed to determine the survival rate in breast cancer patients based on neoadjuvant chemotherapy (NAC) response and regimen. MethodsThis was an observational analytic study with a retrospective design. The population was breast cancer patients at our institution who had undergone NAC. Kaplan–Meier analysis using the log-rank method was used to determine the level of survivability (overall survival [OS] and disease-free survival [DFS]) of patients based on chemotherapy response and regimen. ResultsThe NAC overall response rate of breast cancer patients was 93.17 %, whereas the non-response rate was 6.83 %. Significant differences existed in the DFS of patients by chemotherapy response (p = 0.010). Patients with a complete response had a mean survival of 71.37 ± 2.92 months, those with progressive disease had a mean survival of 64.80 ± 15.58 months, and overall patients had a mean survival of 68.56 ± 10.452 months. Patients with a complete response had a mean recurrence time of 69.54 ± 7.48 months; this was 57.53 ± 19.06 months in those with progressive disease, for an overall time of 65.41 ± 13.81 months. No significant difference existed between the NAC regimens in OS and DFS (p = 0.901 and p = 0.798, respectively). ConclusionGenerally, the response to NAC in breast cancer was very good. The DFS rates were significantly different from the chemotherapy response but not from the NAC regimen.

Predictors of the efficacy of intraoperative radiotherapy in organ-preserving treatment of early breast cancer

Background. Despite the improvement in combined modality treatment of early breast cancer (BC), the rate of locoregional recurrence remains in the range of 7-15 %. Therefore, the search for prognostic factors for BC is of great significance. The aim of the study was to estimate the relationship between clinical and morphological parameters and 10-year recurrence-free survival rate in BC patients after combined modality treatment including intraoperative radiotherapy (IOLT). Material and Methods. The study enrolled 383 patients with morphologically verified T1-3N0-1M0 stage breast cancer. The median age of the patients was 53 years (range: 28 to 80 years). All patients underwent breast-conserving surgery with IOLT delivered to the tumor bed at a single dose of 10 Gy (24.8 Gy according to the iso-effect). External beam radiation therapy (EBRT) to the conserved breast was given in the postoperative period. Results. Within the 10-year follow-up, 20 (5.2 %) locoregional recurrences occurred, of which 7 (35 %) developed with a primary tumor size of ≤ 2 cm (T1), and most recurrences - 13 (65 %) were detected with the primary tumor size corresponding to T2-3. In patients with luminal A subtype of BC and in patients with triple negative BC, the recurrence rates were 5 % and 45 %, respectively. The 10-year survival rate of patients after combined modality treatment with IOLT was 94.8 %. Conclusion. The results obtained indicate the relationship between the recurrence rate and clinical/ morphological parameters of the tumor, such as tumor size and molecular subtype. These parameters should be taken into account when planning treatment in patients with early BC.

Impact of hypofractionated adjuvant radiotherapy on complication rate in breast cancer patients with implant-based immediate reconstruction

Hypofractionated radiotherapy in the treatment of breast cancer patients has a signifiant advantage over conventional fractionation due to the shorter duration of treatment course while maintaining its antitumor effiacy. Usage of hypofractionated regimens may be restricted in patients with immediate breast reconstruction because of higher rate of complications. The aim of this study is to evaluate the incidence of complications in the reconstructed breast after hypofractionated radiotherapy. The study involved 100 patients with breast cancer after immediate implant-based breast reconstruction who underwent an adjuvant course of external beam radiation therapy with a single dose of 2.67 Gy to a total dose of 40.05 Gy. In our study the incidence of capsular contracture is 8 %, infectious complications – 2.3 %, protrusion – 4.6 %. The total incidence of complications is 15 %, which does not exceed the incidence in conventional fractionation.

Exosomal miRNA-223-3p derived from tumor associated macrophages promotes pulmonary metastasis of breast cancer 4T1 cells

Research about the effect of exosomes derived from tumor associated macrophages (TAM-exos) in the distant organ metastasis of breast cancer is limited. In this study, we found that TAM-exos could promote the migration of 4T1 cells. Through comparing the expression of microRNAs in 4T1 cells, TAM-exos, and exosomes from bone marrow derived macrophages (BMDM-exos) by sequencing, miR-223-3p and miR-379-5p were screened out as two noteworthy differentially expressed microRNAs. Furthermore, miR-223-3p was confirmed to be the reason for the improved migration and metastasis of 4T1 cells. The expression of miR-223-3p was also increased in 4T1 cells isolated from the lung of tumor-bearing mice. Cbx5, which has been reported to be closely related with metastasis of breast cancer, was identified to be the target of miR-223-3p. Based on the information of breast cancer patients from online databases, miR-223-3p had a negative correlation with the overall survival rate of breast cancer patients within a three-year follow-up, while Cbx5 showed an opposite relationship. Taken together, miR-223-3p in TAM-exos can be delivered into 4T1 cells and exosomal miR-223-3p promotes pulmonary metastasis of 4T1 cells by targeting Cbx5.

Efficacy, cardiotoxicity and factors affecting pathologic complete response of neoadjuvant chemotherapy with anthracycline-containing verses anthracycline-free regimens plus dual HER2 blockade for HER2-positive early-stage breast cancer: a retrospective study.

The aim of this study was to compare the efficacy, cardiotoxicity and factors affecting pathologic complete response (pCR) of neoadjuvant chemotherapy (NACT) regimen TCbHP (docetaxel/nab-paclitaxel, carboplatin, trastuzumab and pertuzumab) and AC-THP (doxorubicin, cyclophosphamide followed by docetaxel/nab-paclitaxel, trastuzumab and pertuzumab) for human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer at a retrospective cohort. This retrospective study included the patients with HER2+ early-stage breast cancer who received NACT with the regimen TCbHP or AC-THP and then underwent surgery from 2019 to 2022. pCR rate and breast-conserving rate were calculated to evaluate the efficacy of the regimens. Left ventricular ejection fraction (LVEF) from echocardiograms and abnormal electrocardiographs (ECGs) were collected to evaluate the cardiotoxicity of the two regimens. Association between the characteristics of the breast cancer lesions by magnetic resonance imaging (MRI) and the pCR rate were also explored. A total of 159 patients were enrolled, including 48 patients in the AC-THP group and 111 patients in the TCbHP group. The pCR rate of the TCbHP group 64.0% (71/111) was significantly higher than that of for the the AC-THP group 37.5% (18/48) (P=0.002). Estrogen receptor (ER) status (P=0.011, OR: 0.437, 95% CI: 0.231-0.829), progesterone receptor (PR) status (P=0.001, OR: 0.309, 95% CI: 0.157-0.608) and IHC HER2 status (P=0.003, OR: 7.167, 95% CI: 1.970-26.076) were significantly correlated with the pCR rate. LVEF decreased at 6 and 12 months after treatment in the AC-THP group (P=0.024 and 0.040), which only decreased after 6 months of treatment in the TCbHP group (P=0.048). Post-NACT MRI characteristics including mass features (P<0.001) and enhancement type (P<0.001) were significantly associated with pCR rate. Early-stage HER2+ breast cancer treated with the TCbHP regimen has a higher pCR rate than the AC-THP group. The TCbHP regimen appears to have lower cardiotoxicity than the AC-THP regimen in terms of LVEF. Mass features and enhancement type at post-NACT MRI significantly associated with the pCR rate of breast cancer patients.

Polyphyllin VII protects from breast cancer-induced osteolysis by suppressing osteoclastogenesis via c-Fos/NFATc1 signaling

Bone is a preferred metastatic site of advanced breast cancer and the 5-year overall survival rate of breast cancer patients with bone metastasis is only 22.8%. Targeted inhibition of osteoclasts can treat skeletal-related events (SREs) in breast cancer patients. Polyphyllin VII (PP7), a pennogenyl saponin isolated from traditional Chinese herb Paris polyphylla, exhibits strong anti-inflammatory and anti-cancer activities. In this study, we evaluated the effect of PP7 on metastatic breast cancer-induced bone destruction in vivo and the underlying mechanisms. We found that intraperitoneal injection of 1 mg/kg PP7 significantly ameliorated the breast cancer MDA-MB-231 cell-induced osteolysis in mice. Mechanistically, PP7 (0.125–0.5 μM) inhibited the conditioned medium of MDA-MB-231 cells (MDA-MB-231 CM)-induced osteoclast formation in bone marrow-derived macrophages (BMMs). Furthermore, PP7 markedly reduced MDA-MB-231 CM-induced osteoclastic bone resorption and F-actin rings formation in vitro. During MDA-MB-231 CM-induced osteoclastogenesis, the activation of c-Fos and NFATc1 signaling was significantly downregulated by PP7, and finally osteoclast-related genes such as Oscar, Atp6v0d2, Mmp9 and β3 integrin were decreased. In addition, the formation of osteoblast was promoted by PP7 treatment. Our current findings revealed PP7 as a potential safe agent for preventing and treating bone destruction in breast cancer patients with bone metastases.

147P Germline BRCA mutation status and response to neoadjuvant systemic therapy in breast cancer

It remains inconclusive whether germline BRCA mutation affects the response of neoadjuvant systemic therapy in breast cancer. Here, we present a retrospective analysis which estimated the pathologic complete response (pCR) rate in breast cancer patients according to gBRCA1/2 mutation status. We reviewed a total of 442 breast cancer patients who underwent gBRCA1/2 tests and received neoadjuvant chemotherapy in 2 institutions between 2001 and 2022. Chemotherapy response was compared between patients with or without deleterious BRCA1/2 mutation and we assessed the association of the pCR rate and clinical characteristics of the patients. For pCR rates, the ypT0/is ypN0 definition was used as a primary end point. We detected pathogenic BRCA1/2 mutations in 145 (32.8%) of the 442 patients, 83 (18.8%) in BRCA1 and 62 (14.0%) in BRCA2. Overall pCR rate was 34.6% (153/442). The pCR rate was 37.9% (55/145) and 33.0% (98/297) for gBRCA1/2 carriers and non-carriers, respectively. Germline BRCA1/2 mutation status, mutation type and locus were not significantly different from a pCR rate (OR:0.806, 95% CI=0.533-1.219, P =0.306). With respect to the demographic and clinicopathological characteristics, higher pCR rate observed in breast cancer with hormone-receptor negative (OR:2.845, 95%CI 1.791-4.520, p<0.001) and HER2 negative (OR:2.823, 95%CI=1.6-4.984, p<0.001) tumor and high ki-67 level (OR:2.165, 95%CI 1.347-3.480, p=0.001), irrespective of gBRCA1/2 mutation. In this analysis, patients with gBRCA1/2 mutations showed no significantly different response in neoadjuvant systemic therapy. Further large-scale analysis with survival data may provide robust evidence on the impact of the gBRCA1/2 mutation status for breast cancer patients.

Pogostone attenuates osteolysis in breast cancer by inhibiting the NF-kB and JNK signaling pathways of osteoclast

AimsBreast cancer is the most prevalent cancer in females, and approximately 70 % of all patients have evidence of metastatic bone disease, which substantially affects the quality of life and survival rate of breast cancer patients. Osteoporosis has become a global public health problem, and the abnormal activation of osteoclasts is the key to the progression of osteoporosis and the key to both diseases lies in the osteoclasts. Effective drug treatments are lacking and there is an urgent need to explore new drugs. Materials and methodsWe observed the effects of pogostone (PO) on osteoclast differentiation, bone resorption function and other indicators, and F-actin ring formation by using Trap staining, SEM and immunofluorescence, and further explored the targets of pogostone in regulating osteoclast differentiation and function using qPCR and Western Blot. In addition, we used CCK 8, Transwell, and flow cytometry to study the effects of pogostone on proliferation, invasion, migration, and apoptosis of MDA-MB-231 cells. Animal models were also constructed for in vivo validation. Key findingsPogostone inhibits osteoclast differentiation, bone resorption, formation of F-actin ring, and the expression of specific genes by attenuated NF-kB degradation and phosphorylation of JNK. In vitro, pogostone suppresses invasion of breast cancer cells, migration, and promotes their apoptosis. In mouse models, pogostone attenuated osteoclast formation and bone resorption, blocked breast cancer cells migration, and supprsed breast cancer-induced osteolysis and ovariectomized (OVX)-mediated osteoporosis. SignificanceThese biological functions of pogostone make it a potential drug for treatment of breast cancer-associated bone metastasis in the future.

Abstract 3983: Defining the role of FANCA in breast cancer development and cell cycle progression

Abstract FANCA is one of the 22 known Fanconi anemia (FA) pathway genes and is indispensable for interstrand crosslink (ICL) repair. It is reported that FANCA is responsible for about 64% of FA cases and one important clinical characterization of FA patients is predisposition to cancer. However, analysis of TCGA database reveals that FANCA level is elevated in breast cancer patients, especially in ER- breast cancer, which is associated with the methylation status at the S-shore of CpG island ahead of FANCA gene. Moreover, the FANCA level is negatively correlated with the survival rate of breast cancer patients. To understand the implication of FANCA in breast cancer development, we have targeted FANCA by either CRISPR mediated knock-out (KO) or shRNA mediated knockdown (KD) in MDA-MB-231 breast cancer cells. Our data suggest that depletion of FANCA protein inhibits breast cancer growth both in vitro and in vivo. On the other hand, overexpressing FANCA in low-FANCA breast cancer cell line MDA-MB-468 promotes cancer cell proliferation. Cell cycle profiling reveals an inefficiency of MDA-MB-231 FANCA KO cells in G1 to S transition due to p21 and p27 upregulation in FANCA KO cells. In addition, the proliferation inefficiency in MDA-MB-231 FANCA KO cells is caused by Rb hypophosphorylation. Therefore, we conclude that FANCA contributes to the breast cancer development by promoting cell cycle progression through Rb/E2F signaling pathway. Our immunoprecipitation (IP) results indicate that in MDA-MB-231, FANCA is interacting with HES1, which is a transcription suppressor that binds to the promoter region of CDKN1A and CDKN1B to promote cell cycle progression, explaining how FANCA participates in cell cycle progression in breast cancer. Citation Format: Liang Luo, Wenjun Liu, Anna Palovcak, Fenghua Yuan, Fang Li, Daniel Calkins, Yan Li, Karoline Briegel, Daniel Bilbao, Evan Roberts, Christian Mason, Zhao-Jun Liu, Sylvia Daunert, Yanbin Zhang. Defining the role of FANCA in breast cancer development and cell cycle progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3983.

The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis.

Parafibromin is a protein encoded by the oncosuppressor CDC73 gene, whose mutation results in hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma. Down-regulation of parafibromin is linked to lung, gastric, colorectal, and ovarian cancer tumorigenesis. Parafibromin expression was detected by RT-PCR, bioinformatics analysis, Western blot, and immunohistochemistry; and compared with clinicopathological characteristics of breast cancer. CDC73-related genes and pathways were analyzed using bioinformatics analysis. Parafibromin expression was increased in breast cancer compared to normal tissues at both mRNA and protein levels (p<0.05). Among triple-negative breast cancers, it was higher in basal-like 1 than basal-like 2 patients (p<0.05) and mesenchymal than immunomodulatory patients (p<0.05). CDC73 mRNA expression was positively correlated with white race, non-infiltrating immune cells, favorable luminal subtypes of PAM50, and prognosis of breast cancer patients (p<0.05). The differential genes of CDC73 were classified into enzyme inhibitors, peptidase, and keratinization by KEGG (p<0.05). Similarly, it was classified into ribosomes, TGF-β, oxidation phosphorylation, inositol phosphate metabolism, arachidonic acid metabolism, linoleic acid metabolism, ERBB, and VEGF signaling pathways by GSEA (p<0.05). The positively-correlated genes of CDC73 were involved in cell mobility, response to interferon α, nuclear pore and basket, and histone methyltransferase. The negatively-correlated genes of CDC73 were involved in the mitochondrial respiratory chain, thermogenesis, and ribosomes. Parafibromin expression was higher in invasive ductal than lobular carcinoma (p<0.05) and mucinous adenocarcinoma than others (p<0.05). Parafibromin immunoreactivity as an independent factor was positively associated with an increased overall survival rate of breast cancer patients (p<0.05). These findings suggest that up-regulation of parafibromin in breast cancer patients is closely linked to a favorable prognosis. It is involved in tumorigenesis and subsequent progression by regulating metabolism, ribosomes, and cytokines.

The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy

BackgroundDisseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient’s pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow.MethodsA total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab.ResultsAt baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00).ConclusionThis is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.

Numerical Simulation of Nonlinear Dynamics of Breast Cancer Models Using Continuous Block Implicit Hybrid Methods

In the search for causes and cures of cancer diseases, many mathematical models developed have resulted in systems of nonlinear stiff ordinary differential equations. With these models, many numerical estimates of biological knowledge of the parameters have been obtained, a number of phenomena interpreted, and predictions were made in order to gain further knowledge of cancer development and possible treatment. In this study, numerical simulations of the models were performed using continuous block implicit hybrid methods and the results obtained support the theoretical and clinical findings. We analyzed the interactions among the various tumor cell populations and present the results graphically. From the graphical representation of results, one can clearly see the effects of all the tumor cell populations involved in the competition, as well as the effects of some treatments by the applications of some therapeutic agents which have been heavily used in the clinical treatments of breast cancer. The treatments in the past were mostly conventional chemotherapies, which were used either singly (alone) or in combination with each other or other therapies, and all played vital roles, except for the side effects that these therapies incur in normal tissues and organs. Thus, from recent research works, it is now clear that in many cases they do not represent a complete cure. Therefore, the need to address not only the preventative measures of breast cancer, but also more successful treatment, is clear, and can be successfully achieved to increase the survival rate of breast cancer patients.

A Study to Assess the Knowledge Regarding Self-Breast Examination on Prevention of Breast Cancer Among Women Attending OPD in Sree Balaji Medical and College And Hospital

Self-examination of the breasts is less expensive than mammography. Breast cancer can be discovered sooner, and women's survival rates can be raised. Rural residents have limited access to medical treatment and have a poorer educational position. As a result, it is critical that they be educated about breast cancer prevention and early diagnosis by systematic breast self-examination. Breast cancer risk begins to climb in a woman's early thirties and reaches an all-time high by the time she reaches her sixth decade. Because women between the ages of 30 and 60 are at high risk, an educational programme for them would be quite useful. Because the perceived threat of breast cancer should inspire children to practise breast self-examination on a regular basis, improved knowledge about breast cancer and competence to do breast self-examination at this age would be useful. According to a study, the five-year survival rate of breast cancer patients is 75 percent, and it is suggested that 50 percent of all breast cancer patients worldwide could have their lives extended by increasing public awareness through early detection and effective treatment at the community level.

Study on Breast Cancer in Kazakhstan Using the Functional Time Series.

In Kazakhstan and Central Asia, breast cancer (BC) is the most common malignancy among women. However, no large-scale study on breast cancer using the functional time series approach has been carried out in Kazakhstan. A functional assessment of the age-period-cohort model (APC) and the survival rate (period 2017-2021) was used in the retrospective study. Clinical and demographic information on patients was analysed, including age, gender, region of residence, kind and stage of tumour, occupation, socioeconomic standing, nationality, and specifics of treatment and its outcomes. Additionally, the relationship between nationality, stage, and residency region and the survival rate of breast cancer patients was investigated too. The data of n=22,736 breast cancer patients were analysed. The highest number of breast cancer cases reported was 4,945 (21.7%), in 2019. In 2021, n =4,939 (21.7%) cases were detected, while in 2020, n=4,222 (18.6%) cases were observed. The patients with breast cancer in stages I and Ia were recognized in 6,585 (29% of cases), while those in stages Ib and Ic were confirmed in 8687 (38.2% of cases). In n=10,147 (44.6%) cases, a malignant tumour of the upper outer quadrant of the breast (C50.4) was predominant. Kazakhs made up the majority (n=10,939, 48.1%) of patients with a primary validated diagnosis of breast cancer, followed by Russians (n=7527, 33.1%). Germans had the lowest survival rate overall (11.4 ± 1.7 months) (p ≤ 0.05) (95% CI: 8.0-14.7 months). Uzbeks showed relatively high survival rates of 18.3 ± 1.6 months (95% CI: 15.1-21.5 months) (p ≤ 0.05). The Aktobe region had the lowest breast cancer survival rates, measuring 12.1±0.9 months (95% CI: 10.3-13.9 months) (p ≤ 0.05). The highest survival rates, 18.0±1.3 months (95% CI: 15.5-20.5 months) and 17.9±1.4 months (95% CI: 15.3-20.7 months), were seen in Shymkent and Zhambyl regions (p ≤ 0.05), respectively. The prevalence of breast cancer increases after 37.5 years, according to the results of the APC analysis, with an indicator of 0.572 (95% CI: -0.41 - 1.56), maintaining a steady upward trend in the age range from 42.5 years to 62.5 years. Despite a slight drop in the disease's frequency, the incidence of breast cancer in women 37.5 years and older has been stable over the past five years. Additionally, it was shown that the country's northern regions had a higher incidence of breast cancer cases than the southern and western regions. Our results show the significance of demographic characteristics such as age and location for the development of preventive measures and effective treatment.

Chinese Herbal Medicine Improved Survival in Stage IV Breast Cancer Patients: Data Mining of the Incorporated Taiwan Cancer Registry Database and Hospital Database.

According to recent research, breast cancer has become the most commonly diagnosed non-skin cancer type among the entire population. Meanwhile, Chinese herbal medicine (CHM) has become an important therapy to improve the survival rate and quality of life in metastatic cancer patients, as part of a wider trend toward more personalized medicine. However, there is a lack of research in terms of the association between stage IV breast cancer and CHM. Therefore, this study aimed to investigate the association between CHM and the survival rate in breast cancer patients at different cancer stages, with a particular focus on patients diagnosed with stage IV. Patients with an initial diagnosis of breast cancer identified from the Taiwan Cancer Registry Database (TCRD) and China Medical University Hospital (CMUH) database were included in this study. Demographic characteristics including gender, age, and comorbidities were evaluated. Between-group differences for continuous and categorical variables were evaluated by the Student's t-test and Chi-square test, respectively. Patients diagnosed with breast cancer were recruited and divided into cohorts of CHM users and non-users with a 1:1 propensity score matching. The survival of breast cancer patients was assessed by the Cox proportional hazard model. The cumulative incidence of survival was assessed by Kaplan-Meier analysis. The adjuvant CHM treatment was associated with a higher survival rate in stage IV breast cancer patients (HR: 0.45, 95% CI: 0.2853-0.7044]. Additionally, the use of CHM had a positive impact on survival in stage IV breast cancer patients who had received surgery (P: .0273, HR: 0.3406, 95% CI: 0.1309-0.8865), chemotherapy (P: .0004, HR: 0.3893, 95% CI: 0.231-0.656), and hormone therapy (P: .0013, HR: 0.3491, 95% CI: 0.1836-0.6636). In terms of the specific CHM associated with survival, Zhi-Gan-Cao-Tang (ZGCT), Phellodendron chinense Schneid. (huang-bai), and Paeonia lactiflora Pall. (chi-shao) were the 3 most commonly prescribed herbal medicines correlated with a higher survival rate among stage IV breast cancer patients. CHM associated with conventional management achieved significant survival benefits in patients with stage IV breast cancer. Additional randomized controlled trials for prospective study are recommended for further validation.

An inflammatory-related genes signature based model for prognosis prediction in breast cancer.

Breast cancer has become the most common malignant tumor in the world. It is vital to discover novel prognostic biomarkers despite the fact that the majority of breast cancer patients have a good prognosis because of the high heterogeneity of breast cancer, which causes the disparity in prognosis. Recently, inflammatory-related genes have been proven to play an important role in the development and progression of breast cancer, so we set out to investigate the predictive usefulness of inflammatory-related genes in breast malignancies. We assessed the connection between Inflammatory-Related Genes (IRGs) and breast cancer by studying the TCGA database. Following differential and univariate Cox regression analysis, prognosis-related differentially expressed inflammatory genes were estimated. The prognostic model was constructed through the Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the IRGs. The accuracy of the prognostic model was then evaluated using the Kaplan-Meier and Receiver Operating Characteristic (ROC) curves. The nomogram model was established to predict the survival rate of breast cancer patients clinically. Based on the prognostic expression, we also looked at immune cell infiltration and the function of immune-related pathways. The CellMiner database was used to research drug sensitivity. In this study, 7 IRGs were selected to construct a prognostic risk model. Further research revealed a negative relationship between the risk score and the prognosis of breast cancer patients. The ROC curve proved the accuracy of the prognostic model, and the nomogram accurately predicted survival rate. The scores of tumor-infiltrating immune cells and immune-related pathways were utilized to calculate the differences between the low- and high-risk groups, and then explored the relationship between drug susceptibility and the genes that were included in the model. These findings contributed to a better understanding of the function of inflammatory-related genes in breast cancer, and the prognostic risk model provides a potentially promising prognostic strategy for breast cancer.

CBX3 promotes breast cancer progression and high level of CBX3 predicts poor prognosis in patients.

Breast cancer is one of the leading cancer deaths around the world. Targeted drugs have greatly increased the survival rate of breast cancer patients in recent years. But in some patients, the current regimen is still ineffective. Therefore, more therapeutic targets for treating breast cancer are demanding. The core heterochromatin-related genes of breast cancer were identified by utilizing prognostic survival analysis and multivariate Cox hazard proportional regression analysis. Both breast cancer and adjacent normal tissue were collected and analyzed with western blot and immunohistochemistry. Colony formation assay, CCK-8 assay, and EdU assay were used to measure the effect of CBX3 on breast cancer cell growth, wound-healing assay and Transwell assay were used to analyze the effect of CBX3 on breast cancer cell migration and invasion. Flow cytometry assay and western blot were used to study the molecular mechanism of CBX3 in breast cancer. High expression of heterochromatin-related proteins CBX3, H2AFY, and SULF1 showed a poor prognosis in patients in both TCGA dataset and GEO datasets. Western blot demonstrated that the expression level of CBX3 was significantly higher in breast cancer than that in adjacent normal tissues. Colony formation assay, CCK-8 assay, and EdU assay showed that the knockdown of CBX3 could significantly inhibit breast cancer cell growth, and the overexpression of CBX3 could promote the growth of breast cancer cells. Transwell assay and wound healing assay showed that knockdown of CBX3 inhibited breast cancer cell migration and invasion, and the overexpression of CBX3 promoted breast cancer cell migration and invasion. Western blot showed that CBX3 might promote breast cancer cell proliferation, invasion, and migration in breast cancer by modulating the ERK1/2 signaling pathway and epithelial-mesenchymal transition (EMT)-related genes. CBX3 was a biomarker of poor prognosis in breast cancer patients. CBX3 promoted the proliferation of breast cancer cells through the ERK signaling pathway, and migration and invasion of breast cancer cells through EMT-related genes. The CBX3/p-ERK1/2 signaling axis might provide a new therapeutic method against breast cancer.

Data augmentation guided breast cancer diagnosis and prognosis using an integrated deep-generative framework based on breast tumor’s morphological information

Breast cancer is the world’s second-largest cause of cancer mortality among women. With the progress of artificial intelligence (AI) in healthcare, the survival rate of breast cancer patients has risen in recent years due to early diagnosis and effective prognosis. However, substantial AI research necessitates a large quantity of high-quality data to perform credible state-of-the-art research. To that end, this study investigates the potentiality of deep generative models including, the tabular variational autoencoder (TVAE) and the conditional generative adversarial network (CTGAN), to generate high-quality synthetic tabular data of breast tumors and support the diagnosis and prognosis of breast cancer. Additionally, this study proposes an integrated interpretable deep-learning framework that includes the synthetic generation of breast cancer data leading to the classification of breast cancer using the interpretable deep attention-based model TabNet based on the domain of breast cancer research at every stage of the research framework. The research findings are justified using benchmark breast cancer datasets. After rigorous investigation, it was found that the TVAE model outperformed the synthetic generation of breast tumor data with a Chi-Squared test(CS test) score of 0.916 (prognosis) and 0.964 (diagnosis) and a Kolmogorov Smirnov test(KS test) score of 0.887 (prognosis) and 0.928 (diagnosis). In the classification stage, despite being trained with only synthetically generated data, the interpretable TabNet architecture outperformed all other machine-learning and deep-learning classifiers with an accuracy of 96.66 % in diagnosis and 82.83 % in prognosis.

Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review.

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell's nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC. SIGNIFICANCE STATEMENT: The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients.

Convolutional Neural Networks Improve Radiologists’ Performance in Breast Cancer Screening for Vietnamese patients

ABSTRACT Nowadays, breast cancer is one of the leading cancers in Vietnam, and it causes approximately 6000 deaths every year. The rate of breast cancer patients was calculated as 26.4/100000 persons in 2018. There are 21,555 new cases reported in 2020. However, these figures can be reduced with early detection and diagnosis of breast cancer disease in women through mammographic imaging. In many hospitals in Vietnam, there is a lack of experienced breast cancer radiologists. Therefore, it is helpful to develop an intelligent system to improve radiologists’ performance in breast cancer screening for Vietnamese patients. Our research aims to develop a convolutional neural network-based system for classifying breast cancer X-Ray images into three classes of BI-RADS categories as BI-RADS 1 (“normal”), BI-RADS 23 (“benign”) and BI-RADS 045 (“incomplete and malignance”). This classification system is developed based on the convolutional neural network with ResNet 50. The system is trained and tested on a breast cancer image dataset of Vietnamese patients containing 7912 images provided by Hanoi Medical University Hospital radiologists. The system accuracy uses the testing set achieved a macAUC (a macro average of the three AUCs) of 0.754. To validate our model, we performed a reader study with the breast cancer radiologists of the Hanoi Medical University Hospital, reading about 500 random images of the test set. We confirmed the efficacy of our model, which achieved performance comparable to a committee of two radiologists when presented with the same data. Additionally, the system takes only 6 seconds to interpret a breast cancer X-Ray image instead of 450 seconds interpreted by a Vietnamese radiologist. Therefore, our system can be considered as a “second radiologist,” which can improve radiologists’ performance in breast cancer screening for Vietnamese patients.