Investigating the influence of family-oriented counselling on breastfeeding continuity in mothers experiencing distractions: A randomized controlled trial.

The prevalence of distraction among breastfeeding mothers is on the rise, primarily attributed to the escalating use of media technologies. This study aimed to assess the influence of family-oriented counselling on the continuity of breastfeeding in mothers experiencing distractions. This randomized controlled trial included 120 eligible lactating mothers who accessed postpartum services at comprehensive health centers in Zanjan, a city in northwest Iran from August 21, 2022 to May 10, 2023. Participants were assigned to two groups through block randomization with a block size of four. The intervention group received Family-Oriented Counselling in three sessions at weekly intervals, and the control group received standard postpartum care. The study measured outcomes using the Maternal Distraction Questionnaire and breastfeeding patterns before, monthly, and up to 4 months after counselling. Data analysis employed statistical methods, including the Chi-square test, independent t-test, repeated measures ANOVA, and the Kaplan-Meier method, with a significance level set at P < 0.05. The results showed that the continuation of exclusive breastfeeding was 33 (55 %) in the intervention group and 21 (35 %) in the control group. This difference was statistically significant (p = 0.001). The reduction in distraction scores over time was more pronounced in the intervention group compared to the control group. The between-group effect was found to be statistically significant with an eta effect size of 0.73 (p = 0.001). In conclusion, the study suggests that the implementation of a family-centered intervention was effective in promoting the continuation of breastfeeding and reducing maternal distractions both during breastfeeding and non-breastfeeding activities. This approach proves to be a valuable step in enhancing the health of both mother and child. The findings underscore the importance of considering such interventions in health policymaking.

Comparison of medical image interpretation time between conventional and automated methods of breast ultrasound.

Objective: To compare the medical image interpretation's time between the conventional and automated methods of breast ultrasound in patients with breast lesions. Secondarily, to evaluate the agreement between the two methods and interobservers. Methods: This is a cross-sectional study with prospective data collection. The agreement's degrees were established in relation to the breast lesions's ultrasound descriptors. To determine the accuracy of each method, a biopsy of suspicious lesions was performed, considering the histopathological result as the diagnostic gold standard. Results: We evaluated 27 women. Conventional ultrasound used an average medical time of 10.77 minutes (± 2.55) greater than the average of 7.38 minutes (± 2.06) for automated ultrasound (p<0.001). The degrees of agreement between the methods ranged from 0.75 to 0.95 for researcher 1 and from 0.71 to 0.98 for researcher 2. Among the researchers, the degrees of agreement were between 0.63 and 1 for automated ultrasound and between 0.68 and 1 for conventional ultrasound. The area of the ROC curve for the conventional method was 0.67 (p=0.003) for researcher 1 and 0.72 (p<0.001) for researcher 2. The area of the ROC curve for the automated method was 0. 69 (p=0.001) for researcher 1 and 0.78 (p<0.001) for researcher 2. Conclusion: We observed less time devoted by the physician to automated ultrasound compared to conventional ultrasound, maintaining accuracy. There was substantial or strong to perfect interobserver agreement and substantial or strong to almost perfect agreement between the methods.

Breast Imaging Reporting and Data System (BI-RADS®): a success history and particularities of its use in Brazil.

BI-RADS® is a standardization system for breast imaging reports and results created by the American College of Radiology to initially address the lack of uniformity in mammography reporting. The system consists of a lexicon of descriptors, a reporting structure with final categories and recommended management, and a structure for data collection and auditing. It is accepted worldwide by all specialties involved in the care of breast diseases. Its implementation is related to the Mammography Quality Standards Act initiative in the United States (1992) and breast cancer screening. After its initial creation in 1993, four additional editions were published in 1995, 1998, 2003 and 2013. It is adopted in several countries around the world and has been translated into 6 languages. Successful breast cancer screening programs in high-income countries can be attributed in part to the widespread use of BI-RADS®. This success led to the development of similar classification systems for other organs (e.g., lung, liver, thyroid, ovaries, colon). In 1998, the structured report model was adopted in Brazil. This article highlights the pioneering and successful role of BI-RADS®, created by ACR 30 years ago, on the eve of publishing its sixth edition, which has evolved into a comprehensive quality assurance tool for multiple imaging modalities. And, especially, it contextualizes the importance of recognizing how we are using BI-RADS® in Brazil, from its implementation to the present day, with a focus on breast cancer screening.

Bacteriological characteristics of primary breast abscesses in patients from the community in the era of microbial resistance.

Objective: The aim of this study is to evaluate the etiological profile and antimicrobial resistance in breast abscess cultures from patients from the community, treated at a public hospital located in Porto Alegre, Brazil. Methods: This is an retrospective cross-sectional study that evaluated the medical records of patients with bacterial isolates in breast abscess secretion cultures and their antibiograms, from January 2010 to August 2022. Results: Based on 129 positive cultures from women from the community diagnosed with breast abscesses and treated at Fêmina Hospital, 99 (76.7%) of the patients had positive cultures for Staphylococcus sp, 91 (92%) of which were cases of Staphylococcus aureus. Regarding the resistance profile of S. aureus, 32% of the strains were resistant to clindamycin, 26% to oxacillin and 5% to trimethoprim-sulfamethoxazole. The antimicrobials vancomycin, linezolid and tigecycline did not show resistance for S. aureus. Conclusion: Staphylococcus aureus was the most common pathogen found in the breast abscess isolates during the study period. Oxacillin remains a good option for hospitalized patients. The use of sulfamethoxazole plus trimethoprim should be considered as a good option for use at home, due to its low bacterial resistance, effectiveness and low cost.

Outcomes after elevation of serratus anterior fascia flap versus serratus muscle flap in direct-to-implant breast reconstruction following mastectomy: a prospective study.

Objective: The purpose of this study was to compare postoperative pain between SF flap and serratus anterior muscle (SM) in direct-to-implant breast reconstruction. Methods: This is a prospective cohort study that included 53 women diagnosed with breast cancer who underwent mastectomy and one-stage implant-based breast reconstruction from January 2020 to March 2021. Twenty-nine patients (54.7%) had SF elevation, and 24 patients (45.3%) underwent SM elevation. We evaluated patient-reported early postoperative pain on the first day after surgery. Also, it was reported that all surgical complications in the first month and patient reported outcomes (PROs) were measured with the BRECON 23 questionnaire. Results: The serratus fascia group used implants with larger volumes, 407.6 ± 98.9 cc (p < 0.01). There was no significant difference between the fascial and muscular groups regarding the postoperative pain score reported by the patients (2 versus 3; p = 0.30). Also, there was no difference between the groups regarding early surgical complications and PROs after breast reconstruction. Conclusion: The use of SF seems to cause less morbidity, which makes the technique an alternative to be considered in breast reconstruction. Although there was no statistical difference in postoperative pain scores between the fascia and serratus muscle groups.

Impact of Empowerment Theory-Based Nursing Intervention on the Quality of Life and Negative Emotions of Patients Diagnosed with Brain Metastasis Post Breast Cancer Surgery.

Objective: This study explores the impact of a nursing intervention grounded in empowerment theory, focusing on behavioral change, on brain metastasis patients post-breast cancer surgery. Methods: Between June 2021 and June 2023, 102 patients diagnosed with brain metastasis after breast cancer surgery at Bao Ding No.1 Central Hospital were randomized into two groups. The control group (51 patients) received standard nursing care, while the observation group (51 patients) participated in a behavioral change nursing intervention influenced by empowerment theory. The evaluation metrics included measures of negative emotions, compliance with treatment protocols, overall quality of life, and nursing satisfaction, assessed at multiple time points during the study period. Results: The intervention led to significant reductions in negative emotions for all patients when compared to their pre-intervention statuses, with the observation group exhibiting notably lower depression and anxiety scores at one and three months post-intervention (P < 0.05). Additionally, this group achieved higher compliance scores and demonstrated greater improvements in quality of life than the control group (P < 0.05). Nursing satisfaction was also significantly higher in the observation group, with 96.08% reporting high satisfaction compared to 80.39% in the control group (P < 0.05). Conclusion: Implementing a nursing intervention that emphasizes behavioral changes and leverages empowerment theory significantly enhances the quality of life, reduces negative emotions, boosts compliance with treatment, and increases nursing satisfaction among patients with brain metastasis following breast cancer surgery. This suggests that such interventions could be a valuable component of postoperative care for this patient population.

Invasive papillary carcinoma of the breast: A case report.

Invasive papillary carcinoma (IPC) of the breast is a rare form of cancer. The current report documents a case of IPC characterized by a large tumor size and skin involvement. Surgical exploration revealed no evidence of axillary lymph node metastasis in breast cancer. Due to financial constraints, the patient opted solely for anastrozole endocrine therapy at a dosage of 1 mg/day for a period of 5 years post-surgery, foregoing other treatments such as radiotherapy and chemotherapy. Since discharge, 2.5 years have passed, during which the patient has been followed up via phone every 3 months, showing a good prognosis. A literature review indicated that IPC is prevalent amongst the elderly population and can be misdiagnosed due to its morphological, cytomorphological and immunophenotypic overlap with other types of papillary neoplasms. This tumor exhibits a more favorable prognosis compared with IDC, primarily attributed to its advantageous gene and molecular expression patterns, coupled with its decreased invasiveness. Despite limited evidence-based research on the treatment of IPC, the present case report, albeit with limitations, underscores the importance of avoiding over-treatment and suggests the feasibility of combining surgery with endocrine therapy for IPC.

Management of Patients with Breast Biopsy under Anti-Coagulation or Anti-Platelet Therapy: Results of a Survey of German Experts.

Introduction: Pre-therapeutic histologic diagnosis through image-guided core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) for suspicious breast findings is a standard procedure. Despite the moderate risk of bleeding, a significant proportion of patients are on temporary or permanent anti-coagulation therapy (ACT) or anti-platelet therapy (APT). Currently, there are no established guidelines for managing biopsies in such patients, leading to varying approaches in clinical practice. Methods: An online survey was conducted among all members of the breast ultrasound working group at the German Society for Ultrasound in Medicine (DEGUM) and the working group for breast diagnostics at the German Radiology Society (DRG). It included n = 51 questions about individual risk perception of biopsy-related bleeding complications and the specific management of biopsies on ACT/APT. Results: A total of 332 experts participated, with 51.8% reporting the absence of a standardized management plan for breast biopsies on ACT/APT. Concerning specific ACT/APT medications, the survey revealed discrepancies in risk perception and management: The majority preferred discontinuing medication with directly acting oral anti-coagulants (DOACs; CNB: 66.9%; VAB: 91.1%), phenprocoumon (CNB: 74.9%; VAB: 96.7%), or therapeutic heparin (CNB: 46.1%; VAB: 72.7%). However, there was a lower inclination to discontinue acetylsalicylic acid (ASA; CNB: 15.2%; VAB: 50.3%) or prophylactic heparin (CNB: 11.9%, VAB: 36.3%). Conclusion: Breast biopsies for patients on ASA or prophylactic heparin are deemed safe and part of standard clinical practice. However, despite available feasibility studies, conducting breast biopsies on ACT medications such as DOACs or phenprocoumon appears feasible only for a minority of experts.

TP53 Gene Polymorphism at Codon 72 as a Response Predictor for Neoadjuvant Chemotherapy.

Introduction: Breast cancer is the most prevalent cancer in women worldwide, and neoadjuvant chemotherapy is a favored method for achieving pathologic complete response (pCR). The TP53 gene is involved in inducing the response to chemotherapy drugs. Objectives: The present study sought to correlate polymorphism variants at codon 72 with pCR to neoadjuvant chemotherapy. Casuistry and Methods: The study was conducted in the state of Sergipe, in northeastern Brazil. A total of 206 patients with a histopathological diagnosis of breast cancer who underwent neoadjuvant chemotherapy from 2019 to 2022 were included. DNA samples were collected for the evaluation of TP53 polymorphism at codon 72. A prospective evaluation of the cases was conducted to verify the surgical pathologic response after chemotherapy; the Response Evaluation Criteria in Solid Tumors (RECIST) were used. The study was approved by the University of São Paulo Ethics and Research Committee. Results: Of the 168 patients, 44.6% were Arg72Arg, 17.3% were Pro72Pro, and 38.0% were Arg72Pro; pCR was achieved in 21.4% of the patients; 10.1% had progressive disease, 13.7% had stable disease, and 54.2% had a partial pathologic response. The only predictor of pCR in multivariate regression was immunohistochemistry (p < 0.001). In the multivariate analysis, Arg72Pro and Pro72Pro increased the odds of the patient evolving with stable disease. This study was innovative in demonstrating a predictor of stable disease in response to neoadjuvant chemotherapy. Conclusion: TP53 polymorphism at codon 72 is not a predictor of pCR, but it can be a predictor of stable disease.

Prognostic factors for the development of upper limb dysfunctions after breast cancer: the UPLIFT-BC prospective longitudinal cohort study protocol.

INTRODUCTION: Upper limb (UL) dysfunctions are highly prevalent in people after breast cancer and have a great impact on performing activities in daily living. To improve care, a more comprehensive understanding of the development and persistence of UL dysfunctions is needed. Therefore, the UPLIFT-BC study will primarily examine the prognostic value of different factors at the body functions and structures, environmental and personal level of the International Classification of Functioning, Disability and Health (ICF) framework at 1-month post-surgery for persisting UL dysfunctions at 6 months after finishing cancer treatment. METHODS AND ANALYSIS: A prospective longitudinal cohort study, running from 1-week pre-surgery to 6 months post-local cancer treatment, is performed in a cohort of 250 women diagnosed with primary breast cancer. Different potentially prognostic factors to UL dysfunctions, covering body functions and structures, environmental and personal factors of the ICF, are assessed pre-surgically and at different time points post-surgery. The primary aim is to investigate the prognostic value of these factors at 1-month post-surgery for subjective UL function (ie, QuickDASH) at 6 months post-cancer treatment, that is, 6 months post-radiotherapy or post-surgery (T3), depending on the individuals' cancer treatment trajectory. In this, factors with relevant prognostic value pre-surgery are considered as well. Similar analyses are performed with an objective measure for UL function (ie, accelerometry) and a composite score of the combination of subjective and objective UL function. Second, in the subgroup of participants who receive radiotherapy, the prognostic value of the same factors is explored at 1-month post-radiotherapy and 6 months post-surgery. A forward stepwise selection strategy is used to obtain these multivariable prognostic models. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of UZ/KU Leuven (reference number s66248). The results of this study will be published in peer-reviewed journals and will be presented at several research conferences. TRIAL REGISTRATION NUMBER: NCT05297591.

Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer.

Cancer comes in second place on the list of causes of death worldwide. In 2018, the 5-year prevalence of breast cancer (BC), prostate cancer (PC), and colorectal cancer (CRC) were 30%, 12.3%, and 10.9%, respectively. Cannabinoids are chemicals derived from the Cannabis sativa plant; the most investigated cannabinoids are cannabinol, delta 9-tetrahydrocannabinol (Δ9-THC), and cannabidiol. In humans, the endogenous endocannabinoid system consists of endocannabinoids, cannabinoids receptors (CBs), and enzymes that degrade the endocannabinoids. In this review, we will review the most recent literature for evidence that discusses the role of cannabis in the treatment of the three types of neoplasms mentioned. Studies have proved that BC cells express CB receptors; many in-vivo studies showed that cannabinoids cause apoptosis and inhibit proliferation and migration. Also, researchers found that treating BC mice with THC and JWH-133 (CB2 receptor agonist) slowed the tumor growth. Regarding CRC, cannabidiol was found to decrease the viability of chemotherapy-resistant CRC cells and inhibit metastasis by antagonizing the G-protein-coupled receptor 55 (GPR55; a novel cannabinoid receptor) necessary for metastasis. Moreover, cannabidiol had anti-angiogenetic effects by reducing the expression of vascular endothelial growth factor (VEGF) in addition to anti-inflammatory effects. Finally, studies demonstrated that PC cells highly express CB1 and CB2 receptors and that cannabinoids are capable of inhibiting the release of exosomes and microvesicles related to cancer progression. Cannabinoids also have antiproliferative, anti-invasive, anti-fibroblastic, cell cycle arrest, and proapoptotic effects on PC cells.

Out-of-pocket payment and financial risk protection for breast cancer treatment: a prospective study from India.

Background: Available data on cost of cancer treatment, out-of-pocket payment and reimbursement are limited in India. We estimated the treatment costs, out-of-pocket payment, and reimbursement in a cohort of breast cancer patients who sought treatment at a publicly funded tertiary cancer care hospital in India. Methods: A prospective longitudinal study was conducted from June 2019 to March 2022 at Tata Memorial Centre (TMC), Mumbai. Data on expenditure during each visit of treatment was collected by a team of trained medical social workers. The primary outcome variables were total cost (TC) of treatment, out-of-pocket payment (OOP), and reimbursement. TC included cost incurred by breast cancer patients during treatment at TMC. OOP was defined as the total cost incurred at TMC less of reimbursement. Reimbursement was any form of financial assistance (cashless or repayment), including social health insurance, private health insurance, employee health schemes, and assistance from charitable trusts, received by the patients for breast cancer treatment. Findings: Of the 500 patients included in the study, 45 discontinued treatment (due to financial or other reasons) and 26 died during treatment. The mean TC of breast cancer treatment was ₹258,095/US$3531 (95% CI: 238,225, 277,934). Direct medical cost (MC) accounted for 56.3% of the TC. Systemic therapy costs (₹50,869/US$696) were higher than radiotherapy (₹33,483/US$458) and surgery costs (₹25,075/US$343). About 74.4% patients availed some form of financial assistance at TMC; 8% patients received full reimbursement. The mean OOP for breast cancer treatment was ₹186,461/US$2551 (95% CI: 167,666, 205,257), accounting for 72.2% of the TC. Social health insurance (SHI) had a reasonable coverage (33.1%), followed by charitable trusts (29.6%), employee health insurance (5.1%), private health insurance (4.4%) and 25.6% had no reimbursement. But SHI covered only 40.1% of the TC of treatment compared to private health insurance that covered as much as 57.1% of it. Both TC and OOP were higher for patients who were younger, belonged to rural areas, had a comorbidity, were diagnosed at an advanced stage, and were from outside Maharashtra. Interpretation: In India, the cost and OOP for breast cancer treatment are high and reimbursement for the treatment flows from multiple sources. Though many of the patients receive some form of reimbursement, it is insufficient to prevent high OOP. Hence both wider insurance coverage as well as higher cap of the insurance packages in the health insurance schemes is suggested. Allowing for the automatic inclusion of cancer treatment in SHI can mitigate the financial burden of cancer patients in India. Funding: This work was funded by an extramural grant from the Women's Cancer Initiative and the Nag Foundation and an intramural grant from the International Institute of Population Sciences, Mumbai.

Ultrasound-Guided Regional Anesthesia Using a Mixture of Dexamethasone, Dexmedetomidine, and 0.2% Levobupivacaine for Bilateral Breast Cancer Surgery Under a Spontaneous Breathing Opioid-Free Anesthesia: A Case Report.

Breast cancer is unfortunately the most common cancer in women, although survival rates have greatly increased in recent years. Breast surgery can be very aggressive and therefore highly painful, leading to high rates of acute postsurgical pain and chronic pain. In addition to general anesthesia (GA), ultrasound-guided regional anesthesia (RA) is sometimes performed to help reduce acute postoperative pain and consumption of opioids. Although effective, the main limitation of fascial plane blocks is that they require high volumes of local anesthetics, carrying the risk of local anesthetic systemic toxicity. In this article, we present the case of a 41-year-old woman, who refused GA and was successfully operated on for bilateral breast cancer, under a spontaneous breathing opioid-free sedation and ultrasound-guided RA, based on only 0.2% levobupivacaine with the addition of dexamethasone and dexmedetomidine as adjuvants. Despite this, postoperative analgesia lasted for more than 48 hours, and the patient did not require additional analgesia or opioids.

Serum Prolactin Levels as a Novel, Practical Marker for Predicting Malignant Diseases of the Breast.

Background and objective Prolactin (PRL) has a high specificity toward breast cancer (BC), making it a valuable marker in both diagnosis and prognosis. In this study, we aimed to compare serum PRL levels between pre- and post-menopausal women with BC, as well as normal reference values. We also investigated the association of various risk factors with PRL levels in women with BC. Methods The study involved adult women diagnosed with BC based on clinical features and tissue histopathology receiving treatment at a tertiary care center in Pune, India. General and demographic information, anthropometric measurements (height, weight, and BMI), menstrual status (age at menarche and menopausal state), clinical presentation (signs and symptoms), duration of symptoms, and parity were recorded by using a pre-tested proforma based on hospital records or in-person interviews. Serum PRL was measured by the RIA method (sandwich assay). Results A total of 67 women (average age: 47.5 ± 11.8 years; 33 of them post-menopausal) with BC were included in the study. The participants had an average BMI of 24.9 ± 3.5 kg/m2, and 26 (39%) of them were overweight. The majority of women had BC stage IIA disease, involvement of the right side or upper outer quadrant, and had attained menarche after 14 years of age; 47 women had a BC duration of >3 months. Seven women were nulliparous, and the remaining had given birth to their first child before the age of 26 years. The average serum PRL level among the participants was 9.27 ± 7.62 ng/mL, with higher levels found in post-menopausal women compared to pre-menopausal women (11.08 vs. 7.51 ng/mL, respectively; p=0.08). Women with a higher stage and greater duration of disease had significantly higher serum PRL levels (p<0.001 for both). When compared with reference values, pre-menopausal women showed significantly lower (6.25 vs. 10.9, respectively; p=0.001) and post-menopausal women showed significantly higher (8.55 vs. 5.95; p=0.004) serum PRL levels. A positive correlation was found between serum PRL and age at the time of birth of the first child (p=0.068). Conclusions Based on our findings, PRL is an important hormone in the development of BC in women. Therapeutic modulation of PRL may be a realistic and novel approach to curing human BC, either administered alone or in combination with conventional treatments.

Benign Adenomyoepithelioma of the Breast: A Case Report and Review of Imaging Features.

Adenomyoepithelioma (AME) of the breast is a rare tumor that can be benign or malignant and has varied morphological features. We report a case of a 62-year-old female with a history of right breast cancer who presented with abnormal screening mammography. The detection, presentation, and varied imaging characteristics of AMEs are discussed. The nonspecific imaging and histologic appearance of AME are highlighted, emphasizing the need for representative biopsy samples and histopathological review for diagnosis. Our case underlines the importance of wide surgical excision with negative margins in the presence of diagnostic uncertainty, which corresponds with the current recommended treatment for AME to prevent recurrence.

Maximizing microcalcification detectability in low-dose dedicated cone-beam breast CT: parallel cascades-based theoretical analysis.

Purpose: We aim to determine the combination of X-ray spectrum and detector scintillator thickness that maximizes the detectability of microcalcification clusters in dedicated cone-beam breast CT. Approach: A cascaded linear system analysis was implemented in the spatial frequency domain and was used to determine the detectability index using numerical observers for the imaging task of detecting a microcalcification cluster with 0.17 mm diameter calcium carbonate spheres. The analysis considered a thallium-doped cesium iodide scintillator coupled to a complementary metal-oxide semiconductor detector and an analytical filtered-back-projection reconstruction algorithm. Independent system parameters considered were the scintillator thickness, applied X-ray tube voltage, and X-ray beam filtration. The combination of these parameters that maximized the detectability index was considered optimal. Results: Prewhitening, nonprewhitening, and nonprewhitening with eye filter numerical observers indicate that the combination of 0.525 to 0.6 mm thick scintillator, 70 kV, and 0.25 to 0.4 mm added copper filtration maximized the detectability index at a mean glandular dose (MGD) of 4.5 mGy. Conclusion: Using parallel cascade systems' analysis, the combination of parameters that could maximize the detection of microcalcifications was identified. The analysis indicates that a harder beam than that used in current practice may be beneficial for the task of detecting microcalcifications at an MGD suitable for breast cancer screening.

Deciphering the role of apoptosis signature on the immune dynamics and therapeutic prognosis in breast cancer: Implication for immunotherapy.

Background: In breast cancer oncogenesis, the precise role of cell apoptosis holds untapped potential for prognostic and therapeutic insights. Thus, it is important to develop a model predicated for breast cancer patients' prognosis and immunotherapy response based on apoptosis-related signature. Methods: Our approach involved leveraging a training dataset from The Cancer Genome Atlas (TCGA) to construct an apoptosis-related gene prognostic model. The model's validity was then tested across several cohorts, including METABRIC, Sun Yat-sen Memorial Hospital Sun Yat-sen University (SYSMH), and IMvigor210, to ensure its applicability and robustness across different patient demographics and treatment scenarios. Furthermore, we utilized Quantitative Polymerase Chain Reaction (qPCR) analysis to explore the expression patterns of these model genes in breast cancer cell lines compared to immortalized mammary epithelial cell lines, aiming to confirm their differential expression and underline their significance in the context of breast cancer. Results: Through the development and validation of our prognostic model based on seven apoptosis-related genes, we have demonstrated its substantial predictive power for the survival outcomes of breast cancer patients. The model effectively stratified patients into high and low-risk categories, with high-risk patients showing significantly poorer overall survival in the training cohort and across all validation cohorts. Importantly, qPCR analysis confirmed that the genes constituting our model indeed exhibit differential expression in breast cancer cell lines when contrasted with immortalized mammary epithelial cell lines. Conclusion: Our study establishes a groundbreaking prognostic model using apoptosis-related genes to enhance the precision of breast cancer prognosis and treatment, particularly in predicting immunotherapy response.

Acyl-CoA synthetase 4 modulates mitochondrial function in breast cancer cells.

Mitochondria are dynamic organelles that respond to cellular stress through changes in global mass, interconnection, and subcellular location. As mitochondria play an important role in tumor development and progression, alterations in energy metabolism allow tumor cells to survive and spread even in challenging conditions. Alterations in mitochondrial bioenergetics have been recently proposed as a hallmark of cancer, and positive regulation of lipid metabolism constitutes one of the most common metabolic changes observed in tumor cells. Acyl-CoA synthetase 4 (ACSL4) is an enzyme catalyzing the activation of long chain polyunsaturated fatty acids with a strong substrate preference for arachidonic acid (AA). High ACSL4 expression has been related to aggressive cancer phenotypes, including breast cancer, and its overexpression has been shown to positively regulate the mammalian Target of Rapamycin (mTOR) pathway, involved in the regulation of mitochondrial metabolism genes. However, little is known about the role of ACSL4 in the regulation of mitochondrial function and metabolism in cancer cells. In this context, our objective was to study whether mitochondrial function and metabolism, processes usually altered in tumors, are modulated by ACSL4 in breast cancer cells. Using ACSL4 overexpression in MCF-7 cells, we demonstrate that this enzyme can increase the mRNA and protein levels of essential mitochondrial regulatory proteins such as nuclear respiratory factor 1 (NRF-1), voltage-dependent anion channel 1 (VDAC1) and respiratory chain Complex III. Furthermore, respiratory parameters analysis revealed an increase in oxygen consumption rate (OCR) and in spare respiratory capacity (SRC), among others. ACSL4 knockdown in MDA-MB-231 cells led to the decrease in OCR and in SCR, supporting the role of ACSL4 in the regulation of mitochondrial bioenergetics. Moreover, ACSL4 overexpression induced an increase in glycolytic function, in keeping with an increase in mitochondrial respiratory activity. Finally, there was a decrease in mitochondrial mass detected in cells that overexpressed ACSL4, while the knockdown of ACSL4 expression in MDA-MB-231 cells showed the opposite effect. Altogether, these results unveil the role of ACSL4 in mitochondrial function and metabolism and expand the knowledge of ACSL4 participation in pathological processes such as breast cancer.

Nanoparticle-enhanced PD-1/PD-L1 targeted combination therapy for triple negative breast cancer.

Breast cancer with triple-negative subtype (TNBC) presents significant challenges with limited treatment options and a poorer prognosis than others. While PD-1/PD-L1 checkpoint inhibitors have shown promise, their efficacy in TNBC remains constrained. In recent years, nanoparticle (NP) technologies offer a novel approach to enhance cancer therapy by optimizing the tumor microenvironment and augmenting chemo- and immunotherapy effects in various preclinical and clinical settings. This review discusses recent investigations in NP strategies for improving PD-1/PD-L1 blockade-based combination therapy for TNBC. Those include single or multi-therapeutic NPs designed to enhance immunogenicity of the tumor, induce immunogenic cell death, and target immunosuppressive elements within the tumor microenvironment. The investigations also include NPs co-loaded with PD-L1 inhibitors and other therapeutic agents, leveraging targeted delivery and synergistic effects to maximize efficacy while minimizing systemic toxicity. Overall, NP approaches represent a promising avenue for enhancing PD-1/PD-L1 checkpoint blockade-based combination therapy in TNBC and encourage further developmental studies.

Phosphorylation of cell cycle and apoptosis regulatory protein-1 by stress activated protein kinase P38γ is a novel mechanism of apoptosis signaling by genotoxic chemotherapy.

CARP-1, a perinuclear phospho-protein, regulates cell survival and apoptosis signaling induced by genotoxic drugs. However, kinase(s) phosphorylating CARP-1 and down-stream signal transduction events remain unclear. Here we find that CARP-1 Serine (S)626 and Threonine (T)627 substitution to Alanines (AA) inhibits genotoxic drug-induced apoptosis. CARP-1 T627 is followed by a Proline (P), and this TP motif is conserved in vertebrates. Based on these findings, we generated affinity-purified, anti-phospho-CARP-1 T627 rabbit polyclonal antibodies, and utilized them to elucidate chemotherapy-activated, CARP-1-dependent cell growth signaling mechanisms. Our kinase profiling studies revealed that MAPKs/SAPKs phosphorylated CARP-1 T627. We then UV cross-linked protein extracts from Adriamycin-treated HeLa cervical cancer cells with a CARP-1 (614-638) peptide, and conducted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the peptide-bound protein complexes. This experiment revealed SAPK p38γ interaction with CARP-1 (614-638) peptide. Our studies further established that SAPK p38γ, but not other MAPKs, phosphorylates CARP-1 T627 in cancer cells treated with genotoxic drugs. Loss of p38γ abrogates CARP-1 T627 phosphorylation, and results in enhanced survival of breast cancer cells by genotoxic drugs. CARP-1 T627 phosphorylation was also noted in breast tumors from patients treated with radiation or endocrine therapies. We conclude that genotoxic drugs activate p38γ-dependent CARP-1 T627 phosphorylation to inhibit cell growth.