Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by its lack of estrogen, progesterone, and HER2 receptors, leading to limited treatment options and poor prognosis. This review synthesizes current research on the tumor microenvironment (TME) and immune cell crosstalk in TNBC to identify emerging therapeutic opportunities. The TME in TNBC is a complex ecosystem comprising immune cells, fibroblasts, and extracellular matrix components, which significantly influence tumor growth and metastasis. Single-cell RNA sequencing reveals T-cell heterogeneity and identifies prognostic genes. Regulatory T cells (Tregs) play a key role in immunosuppression, with thymidine kinase-1 (TK1) identified as a potential therapeutic target. MUC1-C and CXCL9 modulate the TME, impacting T-cell depletion and macrophage differentiation. Spatial analysis highlights the importance of cell-to-cell interactions in predicting recurrence. Epithelial-mesenchymal transition (EMT) and thermogenesis also influence the TME, while epigenetic modifications, such as HDAC inhibition, can induce pyroptosis and enhance immune cell recruitment. Integrating genomic information with TME analysis is crucial for developing personalized treatments, considering racial disparities in immune infiltration. Emerging therapies targeting immune checkpoints, modulating Treg activity, and inducing pyroptosis hold promise for improving TNBC patient outcomes. Future research should focus on multi-omics data, spatial transcriptomics, and patient-derived models to refine therapeutic interventions.

Triple-negative breast cancer (TNBC) exhibits the highest recurrence and mortality rates among breast cancer subtypes. Approximately one million TNBC cases are diagnosed worldwide annually. Current clinical treatments, primarily chemotherapy regimens based on paclitaxel and anthracycline, are associated with high recurrence rates and low overall survival rates. Platinum drugs, introduced for TNBC treatment, demonstrated a positive effect; however, their high-dose administration inevitably results in toxic side effects and drug resistance. Therefore, identifying agents that sensitize patients to platinum-based therapies is critical. Analysis of the TCGA database revealed that AKT1 and autophagy are activated in breast cancer, playing crucial roles in malignant behavior. Further investigation demonstrated that CBP activates the AKT pathway in MDA-MB-231 cells, while its combination with LY294002 or Triciribine (inhibitors of the PI3K/AKT pathway), suppresses cell proliferation. However, this combination also activates autophagy, a protective mechanism. Inhibition of autophagy with CQ or Baf A1 further increased the proliferation-inhibitory effects of CBP in MDA-MB-231 cells. Notably, the sesquiterpene lactone EM-2 extracted from Elephantopus mollis H.B.K., significantly inhibited both the AKT and autophagy pathways in TNBC cells, demonstrating superior cellular inhibitory effects compared with other AKT or autophagy inhibitors combined with CBP. When CBP was combined with EM-2, cell survival decreased by approximately 36 % compared with CBP monotherapy, while the apoptosis rate increased by 22.8 % after 48 h. The combination of CBP and EM2 also produced the greatest tumor shrinkage in vivo. Interestingly, the CBP (3 mg/kg) + EM-2 (6 mg/kg) group achieved the same tumor shrinkage, with only one-fifth the amount of CBP compared with the CBP (16 mg/kg) monotherapy group. In other words, low doses of EM-2 combined with CBP produced the same anti-tumor effects as high-dose CBP alone. These findings provide a novel strategy for the treatment of CBP using dual AKT and autophagy inhibitors, highlighting potential clinical applications.

Accurate assessment of tumor response to neoadjuvant chemotherapy (NAC) in breast cancer is critical for optimizing treatment strategies. While magnetic resonance imaging (MRI) and mammography are commonly used for response evaluation, they have inherent limitations. Ultrasound (US) has emerged as a promising, cost-effective, and real-time alternative. This study aimed to evaluate the effectiveness of US in tracking tumor regression during NAC and its correlation with pathologic tumor regression grade (TRG).

This study included 282 breast cancer patients undergoing NAC. Tumor size was measured using ultrasound at three key time points: pre-chemotherapy, after four cycles, and post-chemotherapy. Spearman's correlation was used to assess the relationship between US-measured tumor changes and TRG. Multinomial logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the predictive accuracy of the measurements from our US in identifying pathologic complete response (pCR).

Ultrasound is a reliable, real-time imaging tool for monitoring NAC response in breast cancer patients. Its ability to predict pCR and track tumor shrinkage highlights its potential for treatment adaptation. Standardization of US protocols and integration with AI-based analysis may further improve its clinical utility, making it a valuable adjunct in breast cancer treatment monitoring.

The use of anticancer drugs is integral to cancer treatment programs. However, the drawbacks of these chemotherapeutic agents, coupled with the problem of drug resistance, remain significant challenges. To address this, we developed a drug delivery platform based on exosomes derived from HEK293 cells, combined with folic acid-conjugated chitosan (FA-CS). The formulation, FA-CS-PEG-5FU@HEK-EXs, exhibited a polydispersity index (PDI) of 0.140, a zeta size of 188.30 nm, and a zeta potential of 3.60 mV. Its cytotoxicity to healthy tissue was negligible; however, at a dose of 500 μg/mL, the survival rate of breast cancer MDA-MB-231 cells decreased to approximately 50 %. Fluorescence staining indicated that FA-CS-PEG-5FU@HEK-EXs induced cell death in cancer cells by increasing reactive oxygen species levels, compromising the mitochondrial membrane potential, and nucleus. Furthermore, FA-CS demonstrated synergistic effects with 5FU, inducing the necrotic cell death (44.6 %). In conclusion, this study demonstrates that using exosomes to deliver the anticancer drug 5FU enhances the drug's therapeutic efficacy. Moreover, compared to conventional cancer therapies, FA-CS-PEG-5FU@HEK-EXs can minimize systemic side effects in clinical applications while enhancing drug utilization, stability, and cellular uptake, leading to highly effective treatment outcomes. The safe and efficient exosome-based platform with significant potential to inhibit tumor proliferation, offering promising insights for future clinical cancer therapies.

Triple-negative breast cancer (TNBC) is an aggressive malignancy characterized by limited therapeutic options and poor prognosis. Despite advancements in precision oncology, conventional chemotherapy remains the cornerstone of TNBC treatment, often accompanied by debilitating side effects and suboptimal outcomes. This review presents a comprehensive analysis of clinical trials on targeted therapies, aiming to establish a novel, evidence-based treatment strategy exclusively leveraging molecularly targeted agents. By integrating patient-specific genetic profiles with therapeutic responses observed across various clinical trial phases, this approach seeks to optimize efficacy while minimizing toxicity. The proposed targeted therapy combinations hold significant potential to revolutionize TNBC treatment, offering a paradigm shift toward precision medicine and improved patient outcomes.

Currently, there are no effective therapeutic targets for triple-negative breast cancer (TNBC), including hormonal therapy, and it has a poor prognosis because of its rapid proliferation, high invasiveness, and metastatic potential. Therefore, it is expected that the elucidation of the characteristics of TNBC at the molecular level may lead to the development of new therapeutic drugs. In this study, Kaplan-Meier curve analysis showed that high expression levels of fibronectin type III domain-containing protein 3A (FNDC3A) were associated with poor overall survival in patients with TNBC. Furthermore, FNDC3A knockdown was found to suppress the epithelial-to-mesenchymal transition (EMT) and invasion potential as well as the stemness in several TNBC cell lines. In addition, RNA-seq analysis revealed that FNDC3A suppression inhibited the expression of Yes-associated protein 1 (YAP1) and its target genes, which have been reported to regulate cancer cell invasion and stemness. These results suggest that FNDC3A is a novel factor that plays an important role in the malignant progression of TNBC by maintaining cancer stemness and promoting cell invasion and that its function may involve the YAP1 pathway regulation. Therefore, FNDC3A is expected to become a potential therapeutic target for patients with TNBC.

Tumors formed by the unchecked growth of breast cells are known as breast cancer. The second most frequent cancer in the world is breast cancer. It is the most common cancer among females. In 2022, 2,296,840 women were diagnosed with breast cancer. The therapy of breast cancer is evolving through the development of Poly (ADP-ribose) polymerase (PARP) inhibitors, which are offering people with specific genetic profiles new hope as research into the disease continues. It focuses on patients with BRCA1 and BRCA2 mutations. This review summarizes the most recent research on the mechanisms of action of PARP inhibitors and their implications for breast cancer therapy. We review how therapeutic applications are developing and highlight recent studies showing the effectiveness of these medicines whether used alone or in combination. Furthermore, the significance of customized therapy is highlighted in enhancing patient outcomes as we address the function of genetic testing in identifying candidates for PARP inhibition. Recommendations for future research areas to maximize the therapeutic potential of PARP inhibitors are also included, along with challenges and limits in their clinical usage. The objective of this review is to improve our comprehension of the complex interaction between breast cancer biology and PARP inhibition. This knowledge will help to guide screening approaches, improve clinical practice, and support preventive initiatives for people at risk.

Background/Objectives: This study evaluates the impact of clinical, pathological, and treatment-related factors on breast cancer recurrence and overall survival following neoadjuvant chemotherapy and surgery. Patients and Method: A total of 298 patients treated at Diakoneo Diak Klinikum, Schwäbisch Hall, Germany (2010-2021) were analyzed. Key variables included hormone receptor status, molecular subtypes, tumor grade, treatment protocols, and metastatic disease at diagnosis. Results: Recurrence was strongly associated with metastatic disease (p < 0.001) but not with hormone receptor status or molecular subtypes. Platinum/taxane-based chemotherapy was linked to a lower recurrence risk (p = 0.05) compared to anthracycline-based regimens. Patients with recurrence had significantly lower overall survival (27.91% vs. 8.24%, p < 0.001). Logistic regression suggested a trend toward increased recurrence in ER-positive and PR-negative patients, though not statistically significant. These findings emphasize the importance of personalized treatment strategies and highlight the need for future studies incorporating genomic data and residual disease analysis to refine recurrence risk prediction and therapy selection.

Background/Objectives: The primary purpose of this study is to provide a more in-depth insight into various demographic, clinical, and lifestyle factors in relation to breast cancer and to predict the extent to which certain variables described as "predictors" might lead to further investigation. By analyzing a large cohort, we are able to provide valuable and up-to-date information on breast cancer screening, support breast specialists, and further enhance international screening guidelines. Methods: We screened for breast cancer in a population of women aged 50 to 69 years by using the standardized breast cancer imaging screening method (breast mammography) and ultrasonography as a complementary imagistic tool, and we compared the results with the gold standard, breast biopsy. For this, 58,760 women with no known history of breast cancer coming from 4 major regions of Romania (North-East, North-West, South-East, and West) were first evaluated through mammography. Out of these, 3197 women with positive mammograms subsequently underwent a breast ultrasound examination. The remaining 688 patients with positive breast ultrasound were further referred for a breast biopsy. Results: The statistical analysis revealed several predictors such as the body mass index (BMI), positive family medical history of breast cancer, age at first birth, and age at menopause that influenced the progression from mammography (first stage of the screening program) towards echography (additional imaging modality). Furthermore, we established that age, age at first birth, and BMI are significant predictors of progression from echography towards biopsy (the last stage of the screening program). Furthermore, by analyzing the number of positive biopsies (688) out of the total number of patients in the study (58,760), we calculated a total breast cancer detection rate of 8 per 1000 patients. Lastly, by studying the patient demographics in the context of breast cancer (BC) screening, we observed that participants coming from an urban environment presented a higher rate of positive mammographic results as compared to ones of rural provenience. Conclusions: Our study analyzed a large cohort of patients and offers real world data which shows that multiple factors were positively associated with an increased risk of BC. Older age, older age at first birth, and an older menopausal age are all estrogen-dependent risk factors that were linked with an increased breast cancer risk in our study. Furthermore, our findings concerning the rural/urban disparities and regional differences highlight the need for region-specific interventions to address lifestyle risk factors, improve healthcare access, and enhance breast cancer screening and follow-up protocols, particularly in underserved areas like the North-East and South-East regions.

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated the role of epigenetic modifications in the pathogenesis of breast cancer, including drug resistance and efflux characteristics, offering potential new diagnostic and prognostic markers, treatment efficacy predictors, and therapeutic agents. Key modifications include DNA cytosine methylation and the covalent modification of histone proteins. Unlike genetic mutations, reprogramming the epigenetic landscape of the cancer epigenome is a promising targeted therapy for the treatment and reversal of drug resistance. Epidrugs, which target DNA methylation and histone modifications, can provide novel options for the treatment of breast cancer by reversing the acquired resistance to treatment. Currently, the most promising approach involves combination therapies consisting of epidrugs with immune checkpoint inhibitors. This review examines the aberrant epigenetic regulation of breast cancer initiation and progression, focusing on modifications related to estrogen signaling, drug resistance, cancer progression, and the epithelial-mesenchymal transition (EMT). It examines existing epigenetic drugs for treating breast cancer, including agents that modify DNA, inhibitors of histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone demethyltransferases. It also delves into ongoing studies on combining epidrugs with other therapies and addresses the upcoming obstacles in this field.

Triple negative breast cancer (TNBC) is a deadly subtype of breast cancer with limited treatment options. Currently, programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have become the first choice for breast cancer immunotherapies. Despite paclitaxel being considered a cornerstone drug in breast cancer treatment, the effectiveness, safety, and optimal drug selection for its combination with PD-1/PD-L1 inhibitors remain uncertain.

We conducted a systematic review and network meta-analysis, performing a comprehensive literature search across PubMed, Embase, and the Cochrane Library from the inception of each database through May 18, 2024. Selected trials were those that assessed the efficacy and safety of paclitaxel-based PD-1/PD-L1 therapies for the treatment of TNBC. The primary endpoint assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), adverse events (AEs), overall response rate (ORR), and Pathological complete response (pCR). This study is registered in PROSPERO under registration number CRD42023429651.

A total of 8 RCTs meeting our eligibility criteria were included, involving 4626 patients who received either Paclitaxel (Paclitaxel-placebo/chemotherapy) or a combination of durvalumab, pembrolizumab, atezolizumab, toripalimab with paclitaxel. The pooled results demonstrated that Durvalumab combined with Paclitaxel significantly reduced the hazard ratio for OS (surface under the cumulative ranking [SUCRA]: 91.05%) and PFS compared with Paclitaxel alone (SUCRA: 83.52%). Additionally, Durvalumab plus Paclitaxel significantly improved the ORR compared with Paclitaxel (odds ratio [OR]: 2.30; 95% credible interval [CrI]: 1.10-5.20). For safety outcomes, Atezolizumab plus Paclitaxel showed a favorable profile in AEs, with no significant differences observed between groups. In the pCR study, Pembrolizumab plus Paclitaxel was the most effective treatment option (SUCRA: 81.85%).

When combined with paclitaxel, PD-1/PD-L1 inhibitors exhibit a favorable survival benefit. The combination of Durvalumab and paclitaxel represents the optimal treatment option. In the future, attention should be paid to the TNBC subtypes and drug dosage, as these factors may help to design personalized TNBC treatment programs.

Breast cancer has become one of the most serious and widespread public health concerns globally, affecting an increasing number of women-and, in rare cases, men-across the world. It is the most common cancer among women across all countries. In this study, we aimed to evaluate the influence of demographic factors, medical and reproductive history, diagnostic techniques, and hormone receptor status on the development and progression of breast cancer.

A total of 687 female patients from Romania underwent standard breast examination techniques, including clinical breast examination, mammography, ultrasonography, and, ultimately, breast biopsy. Statistical analysis was performed using the R programming language and RStudio software. The study included a comparative analysis and a prediction analysis for malignancy and tumor size (cumulative histological dimension) through logistic and linear regression models.

The comparative analysis identified several variables associated with malignancy: older age (p < 0.001), non-vulnerability (p = 0.04), no daily physical activity (p = 0.002), no re-biopsy (p < 0.001), immunohistochemistry use (p < 0.001), use of larger gauge needles (p < 0.001), ultrasound-guided biopsy (p < 0.001), and vacuum biopsy (p < 0.001). The hormone receptor statuses-estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR)-showed statistically significant differences in distribution across breast cancer B classifications. Logistic regression analysis identified ER, PR, and age as significant predictors of malignancy. Linear regression analysis revealed histopathological results, living environment, geographical region, vulnerability, prior breast examination, and the number of histological fragments as significant predictors of cumulative histological dimension.

Our predictive models demonstrate the impact of demographic factors, medical history, diagnostic techniques, and hormone receptor status on breast cancer development and progression, accounting for a significant portion of the variance in malignancy and cumulative histological dimension.

Triple-negative breast cancer (TNBC) is known to have the worst outcome compared to the other forms of breast cancer. Moreover, molecular markers identified basal-like breast cancer (BLBC) phenotypes to be also related to a worse prognosis. In this study, we evaluated by immunohistochemistry (IHC) the prognostic significance of combining Cytokeratin-19 (CK19), E-cadherin, and Ki-67 tissue expression in triple-negative breast cancer (TNBC) cases presenting a basal-like (BLBC) or a non-basal-like (n-BLBC) phenotype to improve the selection and the monitoring of BC patients with a more aggressive outcome. Herein, when compared to n-BLBC, patients with BLBC showed a positive correlation with lymph node metastasis occurrence and lower survival rates. Immunohistochemistry analysis revealed significantly lower E-cadherin prevalence and higher prevalence of both CK19 and Ki-67 in BLBC when compared to n-BLBC. Spearman correlation showed that E-cadherin is negatively and significantly correlated to CK19 and Ki-67 expressions. Moreover, in BLBC, expressing both CK19 and Ki-67 combined with E-cadherin loss was associated with the worst relapse-free and overall survival. In conclusion, TNBC/BLBC phenotypes simultaneously losing E-cadherin and overexpressing CK19 and Ki-67 markers are the most aggressive forms. This combined analysis could be a predictive marker of poor prognosis.

Breast cancer is one of the most common cancers and the leading cause of cancer death in women. Less than 1% of breast cancer cases are male breast cancers. Although there has been significant progress made in the management of breast cancer, due to its rarity among men, the question of whether men and women with breast cancer have the same treatment response and survival rate still needs to be answered. The primary goal of this study is to compare survival outcomes between male and female breast cancer patients.

This cohort study represents a retrospective and anonymized data analysis of 2162 breast cancer cases (19 males and 2143 females), registered over a period of 12 years, from 1 January 2010 to 31 December 2021, in the Clinic of Obstetrics and Gynecology, Diakoneo Diak Klinikum Schwäbisch Hall, Germany.

According to the Kaplan-Meier survival analysis, the estimated overall 3-year survival rate was 91.1% for women and 88.9% for men. The log-rank test of equality of survival distributions indicated a statistically significant difference in survival times between the two groups (p = 0.009). In the subsequent age-matched Kaplan-Meier analysis, the p-value was below the significance threshold (p = 0.068).

Male breast cancer is a rare disease that may show some particularities in terms of survival compared to female breast cancer.