Breast Cancer Research Articles

Acute toxicity of hypofractionated radiotherapy for Japanese breast cancer patients after surgery: a single center prospective observational study (HyPORT-BC).

This single center prospective observational study was conducted to evaluate the acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery. This study recruited patients who were scheduled for moderately hypo-fractionated radiotherapy including supraclavicular lymph node area (Cohort M) or ultra-hypo-fractionated radiotherapy for the conserved breast (Cohort U) as postoperative treatment for breast cancer. Radiotherapy plans were generated using automated planning system. Irradiation of 42.5Gy/16 fractions (Cohort M) or 26Gy/5 fractions (Cohort U) was delivered, and boost irradiation of 10Gy/5 fractions was added as needed. The primary endpoint was the proportion of grade ≥ 2 acute adverse events within 90days. The toxicities were evaluated using CTCAE ver 5.0. Between January 2023 and December 2023, 123 patients (81 in Cohort M and 42 in Cohort U) were enrolled. All the included patients were Japanese and completed their planned radiotherapy and were also able to be evaluated for acute adverse events. Grade 1/2/3-5 acute adverse events were observed in 67/12/0 for Cohort M and 31/4/0 for Cohort U. The proportion of grade ≥ 2 acute adverse events within 90days was 15% (95% confidence interval 8-24%) for Cohort M and 10% (95% confidence interval 3-23%) for Cohort U. The proportion of acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery was shown to be acceptable in this study.

NKG2D-bispecific enhances NK and CD8+ T cell antitumor immunity

BackgroundCancer immunotherapy approaches that elicit immune cell responses, including T and NK cells, have revolutionized the field of oncology. However, immunosuppressive mechanisms restrain immune cell activation within solid tumors so additional strategies to augment activity are required.MethodsWe identified the co-stimulatory receptor NKG2D as a target based on its expression on a large proportion of CD8+ tumor infiltrating lymphocytes (TILs) from breast cancer patient samples. Human and murine surrogate NKG2D co-stimulatory receptor-bispecifics (CRB) that bind NKG2D on NK and CD8+ T cells as well as HER2 on breast cancer cells (HER2-CRB) were developed as a proof of concept for targeting this signaling axis in vitro and in vivo.ResultsHER2-CRB enhanced NK cell activation and cytokine production when co-cultured with HER2 expressing breast cancer cell lines. HER2-CRB when combined with a T cell-dependent-bispecific (TDB) antibody that synthetically activates T cells by crosslinking CD3 to HER2 (HER2-TDB), enhanced T cell cytotoxicity, cytokine production and in vivo antitumor activity. A mouse surrogate HER2-CRB (mHER2-CRB) improved in vivo efficacy of HER2-TDB and augmented NK as well as T cell activation, cytokine production and effector CD8+ T cell differentiation.ConclusionWe demonstrate that targeting NKG2D with bispecific antibodies (BsAbs) is an effective approach to augment NK and CD8+ T cell antitumor immune responses. Given the large number of ongoing clinical trials leveraging NK and T cells for cancer immunotherapy, NKG2D-bispecifics have broad combinatorial potential.

Simultaneous estimation of paclitaxel and bortezomib via LC-MS/MS: pharmaceutical and pharmacokinetic applications.

Aim & Objective: This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. Materials & Methods: The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Results: Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10mM ammonium acetate. The size of nanoformulation was 133.9±1.97nm, PDI 0.19±0.01 and zeta potential -19.20±1.36mV. Pharmacokinetics showed higher Cmax for PTX-BTZ-NE (313.75±10.71ng/ml PTX, 11.92±0.53ng/ml BTZ) versus free PTX-BTZ (104±13.06ng/ml PTX, 1.9±0.08ng/ml BTZ). Conclusion: Future findings will contribute to the treatment of breast cancer using PTX and BTZ.

ASO Visual Abstract: Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

ASO Visual Abstract: Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

Mobile breast screening services in Australia: A qualitative exploration of perceptions and experiences among rural and remote women aged ≥75 years.

This qualitative descriptive study draws on data collected from a sub-sample of 15 women participating in a national study (n = 60) exploring the breast cancer screening motivations and behaviours of women aged ≥75 years. The study aimed to understand why women living in rural and remote areas might continue accessing mobile breast cancer screening despite being outside the targeted age range. Settings ranged from large towns to very remote communities (according to Monash Modified Model (MMM) classification 3-7) where BreastScreen Australia mobile screening services were available. Interview data from 15 women aged ≥75 years living in rural and remote locations who had used mobile screening services was utilised for this study. In-depth individual interviews were conducted via telephone or online platform (Zoom). These were transcribed verbatim and imported into NVivo software to enable thematic analysis to identify key themes. Many women aged ≥75 years in rural and remote areas expressed clear intentions to continue breast cancer screening, despite no longer being invited to do so. They perceived great value in the mobile service and were highly appreciative for it yet acknowledged limited sources of information about the process of ongoing screening. Few women in rural and remote areas had discussed ongoing breast cancer screening with their general practitioner (GP). More information is required to inform women about the risks and benefits of ongoing screening. Without an invitation to attend screening rural women reported difficulty in knowing when the service would be available. Ongoing notification of the availability of mobile services for women aged ≥75 years in rural areas is recommended.

Association between BMI and success of transaxillary venous port implantation: A retrospective cohort study.

Totally implanted venous access device are widely used for long-term chemotherapy in cancer patients. Previous studies have only focused on the analysis of complications associated with infusion port implantation, ignoring the causes of unsuccessful infusion port implantation. The purpose of this study was to investigate the association between body mass index (BMI) and the success rate of transaxillary intravenous port implantation in breast cancer patients. To review 361 breast cancer patients who underwent intravenous port implantation from January 2021 to September 2021. Baseline data, and surgical data were collected from the patients, and the success rate of puncture of the axillary vein was recorded. The logistic regression analysis and smoothed curve fitting were used to assess the relationship between BMI and the success rate of axillary venipuncture. In addition, subgroup analyses were performed to explore potential interactions. Under ultrasound guidance, 67.3% of patients (243/361) had an infusion port implanted by axillary vein puncture. There was a roughly linear relationship between BMI and the success rate of axillary venipuncture. In the multiple regression equation, BMI was significantly and negatively associated with the success rate of axillary venipuncture (OR = 0.83; 95% CI = 0.77-0.89; p < 0.001). Stratified analysis showed that the relationship between BMI and the success rate of axillary venipuncture was stable and unaffected by other variables. The higher the patient's BMI, the higher the chance of difficult axillary venipuncture or failed cannulation.

Role of textural and radiomic analysis parameters in predicting histopathological parameters of the tumor in breast cancer patients.

Texture and radiomic analysis characterizes the tumor's phenotype and evaluates its microenvironment in quantitative terms. This study aims to investigate the role of textural and radiomic analysis parameters in predicting histopathological factors in breast cancer patients. Two hundred and twelve primary breast cancer patients underwent 18F-FDG PET/computed tomography for staging. The images were processed in a commercially available textural analysis software. ROI was drawn over the primary tumor with a 40% threshold and was processed further to derive textural and radiomic parameters. These parameters were then compared with histopathological factors of tumor. Receiver-operating characteristic analysis was performed with a P-value <0.05 for statistical significance. The significant parameters were subsequently utilized in various machine learning models to assess their predictive accuracy. A retrospective study of 212 primary breast cancer patients was done. Among all the significant parameters, SUVmin, SUVmean, SUVstd, SUVmax, discretized HISTO_Entropy, and gray level co-occurrence matrix_Contrast were found to be significantly associated with ductal carcinoma type. Four parameters (SUVmin, SUVmean, SUVstd, and SUVmax) were significant in differentiating the luminal subtypes of the tumor. Five parameters (SUVmin, SUVmean, SUVstd, SUVmax, and SUV kurtosis) were significant in predicting the grade of the tumor. These parameters showcased robust capabilities in predicting multiple histopathological parameters when tested using machine learning algorithms. Though textural analysis could not predict hormonal receptor status, lymphovascular invasion status, perineural invasion status, microcalcification status of tumor, and all the molecular subtypes of the tumor, it could predict the tumor's histologic type, triple-negative subtype, and score of the tumor noninvasively.

Comparison of predictive models in postoperative nausea and vomiting in patients undergoing breast cancer surgery

BackgroundPost-operative nausea and vomiting remain an unresolved concern in Türkiye and some parts of the world, impacting the quality of the patient's recovery process and diminishing overall satisfaction.ObjectiveThis study was conducted as a descriptive investigation to compare the incidence of nausea and vomiting following breast cancer surgery with the nausea and vomiting risk scores proposed by Apfel and Koivuranta.MethodsThis study was conducted with 100 patients admitted to the General Surgery service of a university hospital between 31 August 2019 and 31 May 2021 for breast cancer surgery. The patient information form developed by the researchers, Apfel Nausea and Vomiting Risk Score, and Koivuranta Nausea and Vomiting Risk Score were used as data collection tools.ResultsIt was identified that 61% of the patients experienced nausea and vomiting within the initial 24 h following surgery. A significant correlation was found between age, post-operative opioid use, motion sickness or history of PONV, and nausea and vomiting (p < 0,05). The sensitivity of the Apfel score obtained was 80%, the specificity was 46%, and the AUC value was 0.686. The sensitivity of the Koivuranta score was 80%, the specificity was 35%, and the AUC value was 0.675 (p < 0.05).ConclusionIt has been observed that patients experience high rates of nausea and vomiting after breast cancer surgery and that the Apfel and Koivuranta Risk Scores are equally applicable in predicting post-operative nausea and vomiting.

TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway

BackgroundHuman epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC.MethodsBioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC.ResultsGRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/β-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/β-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing.ConclusionsOur work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target.

Advocate-BREAST: advocates and patients’ advice to enhance breast cancer care delivery, patient experience and patient centered research by 2025

PurposeThe aims of the Advocate-BREAST project are to study and improve the breast cancer (BC) patient experience through education and patient-centered research.MethodsIn December 2021, an electronic REDCap survey was circulated to 6,918 BC survivors (stage 0–4) enrolled in the Mayo Clinic Breast Disease Registry. The questionnaire asked about satisfaction with BC care delivery, and education and support receive(d) regarding BC linked concerns. Patients also ranked Quality Improvement (QI) proposals.ResultsThe survey received 2,437 responses. 18% had Ductal Carcinoma in Situ, 81% had early breast cancer (EBC), i.e. stage 1–3, and 2% had metastatic breast cancer (MBC). Mean age was 64 (SD 11.8), and mean time since diagnosis was 93 months (SD 70.2). 69.3% of patients received all care at Mayo Clinic. The overall experience of care was good (> 90%). The main severe symptoms recalled in year 1 were alopecia, eyebrow/eyelash thinning, hot flashes, sexual dysfunction, and cognitive issues. The main concerns recalled were fear of BC recurrence/spread; loved ones coping; fear of dying, and emotional health. Patients were most dissatisfied with information regarding sexual dysfunction, eyebrow/eyelash thinning, peripheral neuropathy, and on side effects of immunotherapy/targeted therapies. Top ranking QI projects were: i) Lifetime access to concise educational resources; ii) Holistic support programs for MBC and iii) Wellness Programs for EBC and MBC.ConclusionsPatients with early and advanced BC desire psychological support, concise educational resources, and holistic care.ImplicationsFocused research and QI initiatives in these areas will improve the BC patient experience.

Long non-coding RNA TMEM147 antisense RNA 1/microRNA-124/signal transducer and activator of transcription 3 axis in estrogen receptor-positive breast cancer.

This research aimed to probe the expression of long noncoding RNA TMEM147 antisense RNA 1 (TMEM147-AS1)/micro-RNA (miR)-124/signal transducer and activator of transcription 3 (STAT3) axis in estrogen receptor (ER)-positive breast cancer (BC). Sixty ER-positive BC patients undergoing surgical treatment were gathered. TMEM147-AS1, miR-124, and STAT3 expression levels in BC cells and tissues were measured. The binding sites of TMEM147-AS1 and miR-124, miR-124, and STAT3 were analyzed and validated. The miR-124, STAT3 overexpression (oe) sequences, TMEM147-AS1 oe, and interference sequences and their control sequences were planned and cells were transfected to assess their functions in BC cells biological functions. TMEM147-AS1, as well as STAT3 was extremely expressed and miR-124 was lowly expressed in BC cells and tissues. Interference with TMEM147-AS1 restrained ER-positive BC cell malignant activities. Mechanistically, TMEM147-AS1 could competitively bind miR-124 in refraining miR-124 expression, and STAT3 was a target gene of miR-124. Oe of miR-124 effectively reversed the enhancement of BC cell proliferation and invasion induced by TMEM147-AS1 upregulation. Oe of STAT3 could reverse the inhibitory effect of miR-124 on BC cell malignant behaviors. TMEM147-AS1 has oncogenic activity in ER-positive BC, which may be a result of the altered miR-124/STAT3 axis. Therefore, targeting the TMEM147-AS1/miR-124/STAT3 axis may be a target for ER-positive BC therapy.

Shear-wave elastography as a supplementary tool for axillary staging in patients undergoing breast cancer diagnosis

BackgroundPreoperative evaluation of axillary lymph node status is crucial for the selection of both systemic and surgical treatment in early breast cancer. This study assessed the particular role of additional shear wave elastography (SWE) in axillary staging in patients undergoing initial breast cancer diagnostics.MethodsOne hundred patients undergoing axillary lymph node biopsy due to a sonographically suspicious axillary lymph node were prospectively evaluated with SWE using virtual touch tissue imaging quantification (VTIQ). Mean values of tissue stiffness for axillary tissue and lymph node tissue were measured prior to core-cut biopsy of the lymph node. All lymph nodes were clip-marked during the biopsy. Cut-off values to differentiate between malignant and benign lymph nodes were defined using Youden’s index.ResultsLymph nodes with evidence of malignant tumor cells in the final pathological examination showed a significantly higher velocity as measured by SWE, with a mean velocity of 3.48 ± 1.58 m/s compared to 2.33 ± 0.62 m/s of benign lymph nodes (p < 0.0001). The statistically optimal cutoff to differentiate between malignant and benign lymph nodes was 2.66 m/s with a sensitivity of 69.8% and a specificity of 87.5%.ConclusionsLymph node metastases assessed with SWE showed significantly higher elasticity values compared to benign lymph nodes. Thus, SWE provides an additional useful and quantifiable parameter for the sonographic assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support the guidance of definitive biopsy work-up.Critical relevance statementShear-wave elastography provides an additional useful and quantifiable parameter for the assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support guiding the definitive biopsy work-up.Key PointsSWE is a quantifiable ultrasound parameter in breast cancer diagnosis.SWE shows a significantly higher velocity in malignant lymph nodes.SWE is useful in improving the sensitivity and specificity of axillary staging.Graphical

Supportive care needs after surgery in patients with breast cancer

PurposeThis study aimed to determine supportive care needs and related factors after surgery in patients with breast cancer.MethodsThis cross-sectional study was conducted with 98 breast cancer patients in a Training and Research Hospital in Istanbul between September 2022 and November 2023. The Personal Information Form and the Supportive Care Needs Survey Short Form Turkish version were used to collect data. One-way variance analysis, post hoc (Tukey, LSD), and t-test were used to analyze the data.ResultsThe total scale mean score for women who underwent surgery for breast cancer in the study was 83.95 22.97. Statistically significantly higher total scale scores were observed in younger women and those who received chemotherapy and radiotherapy than in others. The mean physical and daily living subscale scores of those who received chemotherapy and radiotherapy were higher than those who did not (p < .05). The psychology subscale mean scores of those who were young and unemployed were higher than the others (p < .05). The mean sexuality scores of those who were young, those with high education levels, and those who received chemotherapy were higher than the other groups (p < .05). Age factor affects SCN scores in women with breast cancer.ConclusionSupportive care needs are higher among women with breast cancer who are younger and receive chemotherapy and radiotherapy. The physical needs of those who receive chemotherapy and radiotherapy, the psychological needs of those who are younger and unemployed, and the need for support regarding sexuality were greater among those who are younger and with higher education. Nurses should be aware of the specific needs of these disadvantaged groups and provide individualized holistic care.

Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling.

Toll-like receptors (TLRs) are essential receptors involved in inflammation and innate immunity. Various types of cancer cells, as well as innate immune cells, express TLRs. There is mounting proof that TLRs are critical to the development and spread of cancer as well as metabolism. In breast cancer, up-regulated levels of TLRs have been linked to the aggressiveness of the diseases, worse treatment outcomes, and the emergence of therapeutic resistance. Patients with advanced non-resectable, recurring, and metastatic breast cancer currently have few available treatment choices. An intriguing new strategy is an innate immunity-mediated anticancer immunotherapy, either used alone or in conjunction with existing treatments. In fact, several TLR agonists and antagonists have been used in clinical studies for anti-cancer immunotherapy. Consequently, TLRs serve as critical targets for controlling the course of breast cancer and treatment resistance in addition to being implicated in immune responses against pathogen infection and cancer immunology. In this review, we deliver an overview of the most current findings on TLR involvement in the development of breast cancer and treatment resistance.

Integrative radiomics clustering analysis to decipher breast cancer heterogeneity and prognostic indicators through multiparametric MRI

Breast cancer diagnosis and treatment have been revolutionized by multiparametric Magnetic Resonance Imaging (mpMRI), encompassing T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and Dynamic Contrast-Enhanced MRI (DCE-MRI). We conducted a retrospective analysis of mpMRI data from 194 breast cancer patients (September 2019 to October 2023). Using ‘pyradiomics’ for radiomics feature extraction and MOVICS for unsupervised clustering. Interestingly, we identified two distinct patient clusters associated with significant differences in molecular subtypes, particularly in Luminal A subtype distribution (p = 0.03), estrogen receptor (ER) (p = 0.01), progesterone receptor (PR) (p = 0.04), mean tumor size (p < 0.01), lymph node metastasis (LNM) (p = 0.01), and edema (p < 0.01). Our study emphasizes mpMRI’s potential in breast cancer by using radiomics-based cluster analysis to categorize tumors, uncovering heterogeneity, and aiding in personalized treatment strategies.

Neuronal substance P drives metastasis through an extracellular RNA-TLR7 axis.

Tumour innervation is associated with worse patient outcomes in multiple cancers1,2, which suggests that it may regulate metastasis. Here we observed that highly metastatic mouse mammary tumours acquired more innervation than did less-metastatic tumours. This enhanced innervation was driven by expression of the axon-guidance molecule SLIT2 in tumour vasculature. Breast cancer cells induced spontaneous calcium activity in sensory neurons and elicited release of the neuropeptide substance P (SP). Using three-dimensional co-cultures and in vivo models, we found that neuronal SP promoted breast tumour growth, invasion and metastasis. Moreover, patient tumours with elevated SP exhibited enhanced lymph node metastatic spread. SP acted on tumoral tachykinin receptors (TACR1) to drive death of a small population of TACR1high cancer cells. Single-stranded RNAs (ssRNAs) released from dying cells acted on neighbouring tumoural Toll-like receptor 7 (TLR7) to non-canonically activate a prometastatic gene expression program. This SP- and ssRNA-induced Tlr7 gene expression signature was associated with reduced breast cancer survival outcomes. Therapeutic targeting of this neuro-cancer axis with the TACR1 antagonist aprepitant, an approved anti-nausea drug, suppressed breast cancer growth and metastasis in multiple models. Our findings reveal that tumour-induced hyperactivation of sensory neurons regulates multiple aspects of metastatic progression in breast cancer through a therapeutically targetable neuropeptide/extracellular ssRNA sensing axis.

A randomized controlled study of neoadjuvant metformin with chemotherapy in nondiabetic breast cancer women: The METNEO study.

Clinical data demonstrate that metformin exhibits antiproliferative, proapoptotic and antimetastatic actions. Here, correlative molecular studies were undertaken to determine the roles of transmembrane tumour necrosis factor-related apoptosis-inducing ligand death receptors (DRs) and CD133, a glycoprotein biomarker of breast cancer (BC) stem cells, in the advantageous action of metformin on pathological and clinical outcomes in BC patients on neoadjuvant chemotherapy. We randomly assigned 70 nondiabetic BC patients in a 1:1 ratio to either neoadjuvant AC-T chemotherapy (4cycles of adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2, followed by 12 cycles of weekly paclitaxel 80 mg/m2) or AC-T with adjunct metformin (850 mg twice/day). The expressions of DR4, DR5 and CD133 were quantified in excised tissue samples with residual tumour cells. The overall clinical response (odds ratio: 22.67 [2.77-185.18], P= .004), breast-conserving surgery (odds ratio: 3.67 [1.303-10.321], P= .014) and pathological complete response (β =2.49 ±1.13 [0.274-4.712], P= .028) rates were significantly improved in the metformin arm. Tissues obtained from the metformin arm had upregulated mRNA expression of DR4 (Mean delta cycle thresholds ± standard error of the mean: 2.68 ±0.25 vs. 4.87 ±0.53, P= .0003) and DR5 (0.21 ±0.25 vs. 4.29 ±0.95, P= .0004) compared to control arm. The enhanced DR expression negatively correlated with that of CD133 + BC stem cells, which was significantly reduced by metformin at both cytoplasmic/membranous (43.48 vs. 100.00%, P< .0001) and nuclear sites (4.35 vs. 95.00%, P< .0001). Metformin improves clinical and pathological responses to neoadjuvant AC-T chemotherapy in BC via prompting directionally opposite changes in DRs (increments) and CD133 + (decrements) expressions. This study was registered in ClinicalTrials.gov (registration number: NCT04170465, https://clinicaltrials.gov/ct2/show/NCT04170465).

ERα Coregulator TRIM28 Promotes Breast Cancer Progression by Activating the AKT/GSK3β Pathway.

Estrogen receptor α (ERα) promotes the growth and survival of ER-positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin-bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER-associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER-positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3β pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC.

Stem Cell Division and Its Critical Role in Mammary Gland Development and Tumorigenesis: Current Progress and Remaining Challenges.

The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetrical cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of BC stem cell division modes and cause BC. Important regulatory factors such as mammalian Inscuteable mInsc, Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.

Barrier films or dressings for the prevention of acute radiation dermatitis in breast cancer: a systematic review and network meta-analysis.

Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or dressings to the standard of care (SOC) or other interventions were included. We estimated summary odds ratios and mean differences using network meta-analysis with random effects. This study was registered with PROSPERO (ID: CRD42023475021). Fourteen RCTs met inclusion criteria. Six interventions were analysed: 3M™ Moisturizing Double Barrier Cream (MDBC), 3M™ No Sting Barrier Film (BF), Hydrofilm® (HF), Mepitel® Film (MF), Silver Leaf Nylon Dressing and StrataXRT®. HF, MF and StrataXRT® reduced the incidence of moist desquamation compared to SOC (HF: OR = 0.08; p = 0.02; MF: OR = 0.31 p < 0.01; StrataXRT®: OR = 0.22, p = 0.04). The ranking of agents from most to least effective in preventing moist desquamation according to P-scores was HF (92.5%), MF (78.5%), StrataXRT® (70.1%), BF (46.4%), Silver Leaf Nylon Dressing (24.9%), MDBC (22.9%) and SOC (14.7%). Only four RCTs on HF and MF included patient-reported outcome (PRO) assessments that allowed pooling for analysis. HF and MF were more effective in reducing pain, itchiness and burning sensation compared to SOC (p < 0.01 for all symptoms). HF and MF were effective in preventing RD in breast cancer. Future RCTs should compare these interventions to effective cream preparations, such as topical corticosteroids.