Sprouty genes regulate activated fibroblasts in mammary epithelial development and breast cancer.

Stromal fibroblasts are a major stem cell niche component essential for organ formation and cancer development. Fibroblast heterogeneity, as revealed by recent advances in single-cell techniques, has raised important questions about the origin, differentiation, and function of fibroblast subtypes. In this study, we show in mammary stromal fibroblasts that loss of the receptor tyrosine kinase (RTK) negative feedback regulators encoded by Spry1, Spry2, and Spry4 causes upregulation of signaling in multiple RTK pathways and increased extracellular matrix remodeling, resulting in accelerated epithelial branching. Single-cell transcriptomic analysis demonstrated that increased production of FGF10 due to Sprouty (Spry) loss results from expansion of a functionally distinct subgroup of fibroblasts with the most potent branching-promoting ability. Compared to their three independent lineage precursors, fibroblasts in this subgroup are "activated," as they are located immediately adjacent to the epithelium that is actively undergoing branching and invasion. Spry genes are downregulated, and activated fibroblasts are expanded, in all three of the major human breast cancer subtypes. Together, our data highlight the regulation of a functional subtype of mammary fibroblasts by Spry genes and their essential role in epithelial morphogenesis and cancer development.

Knowledge of risk factors and early detection methods toward breast cancer among healthcare workers in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Breast cancer (BC) is the most prevalent cancer among women, and it typically presents late in developing countries like the Democratic Republic of the Congo (DRC), leading to higher mortality rates. Late detection at advanced stages of breast cancer can be attributed to the absence of appropriate screening programs and low levels of awareness. AIMS: To evaluate the level of BC knowledge among healthcare workers (HCWs) and identify determinants of good BC knowledge. METHODS AND RESULTS: An analytical cross-sectional survey was conducted from March 1 to 31, 2022 involving HCWs practicing in Kinshasa, DRC. Data were collected using a questionnaire administered through direct interviews. Bivariate and multivariate regression techniques were applied. The study interviewed 543 HCWs, with a median age of 35 years (interquartile range: 29-43). Of these, 61% had good BC knowledge, while 39% had poor BC knowledge. Multivariate analysis revealed that HCWs aged 50 years and over (adjusted odds ratio [aOR] = 2.3 [1.2-4.5]), female HCWs (aOR = 1.8 [1.1-2.4]), HCWs working in public healthcare facilities (aOR = 1.5 [1.1-2.5]), and HCWs who had received training on BC (aOR = 1.9; 95% CI: 1.5-3.3) were determinants of good BC knowledge. CONCLUSION: This study found that 61% of the surveyed HCWs had good BC knowledge. However, there is still room for improvement in terms of knowledge dissemination. Therefore, it is important to implement continuing medical education programs that focus on raising awareness and improving BC knowledge among HCWs.

Comparison of the effect of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer.

OBJECTIVE: To compare the efficacy of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer. METHODS: A prospective study was conducted in the Department of Breast Surgery, Zhongda Hospital Affiliated to Southeast University. A total of 128 patients with pathologically confirmed breast cancer who were treated by the same surgeon from July 2023 to November 2023 were included in the analysis. All breast operations were performed using electrocautery, and surgical instruments for axillary lymph nodes were divided into ultrasounic-harmonic scalpel group and electrocautery group using a random number table. According to the extent of lymph node surgery, it was divided into four groups: sentinel lymph node biopsy, lymph node at station I, lymph node at station I and II, and lymph node dissection at station I, II and III. Under the premise of controlling variables such as BMI, age and neoadjuvant chemotherapy, the effects of ultrasounic-harmonic scalpel and electrocautery in axillary surgery were compared. RESULTS: Compared with the electrosurgical group, there were no significant differences in lymph node operation time, intraoperative blood loss, postoperative axillary drainage volume, axillary drainage tube indwelling time, postoperative pain score on the day after surgery, and the incidence of postoperative complications (p>0.05). CONCLUSION: There is no significant difference between ultrasounic-harmonic scalpel and electrocautery in axillary lymph node treatment for breast cancer patients, which can provide a basis for the selection of surgical energy instruments.

Designing and implementing a bundle of care for patients with early-stage breast cancer: lessons from a pilot program.

We present a case study on the design and implementation of a value-based bundled package of care for patients with early-stage breast cancer treated in the private health sector in Australia. Value-based healthcare is an essential change to how we deliver healthcare, shifting the focus from paying for individual services provided to a focus on the health outcomes gained over a full cycle of care. The Australian health system has unintentionally created barriers to value-based cancer care through fragmented care pathways and complex funding arrangements where patients can unexpectedly encounter high out-of-pocket costs. A team of clinicians, service providers, health systems and funding experts, private health insurers and consumers have collaborated to design and pilot a complete bundled package of care for breast cancer patients which aims to address these challenges. With 40 patients recruited to date, early evaluation results show positive patient experience of 'joined-up' care and financial transparency. This case study provides a high-level overview of the approach taken to design and implement the Breast Cancer Bundle and the lessons learned for its expansion in both public and private settings.

Peptide Inhibitor Targeting the Extraterminal Domain in BRD4 Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

BRD4 is associated with a variety of human diseases, including breast cancer. The crucial roles of amino-terminal bromodomains (BDs) of BRD4 in binding with acetylated histones to regulate oncogene expression make them promising drug targets. However, adverse events impede the development of the BD inhibitors. BRD4 adopts an extraterminal (ET) domain, which recruits proteins to drive oncogene expression. We discovered a peptide inhibitor PiET targeting the ET domain to disrupt BRD4/JMJD6 interaction, a protein complex critical in oncogene expression and breast cancer. The cell-permeable form of PiET, TAT-PiET, and PROTAC-modified TAT-PiET, TAT-PiET-PROTAC, potently inhibits the expression of BRD4/JMJD6 target genes and breast cancer cell growth. Combination therapy with TAT-PiET/TAT-PiET-PROTAC and JQ1, iJMJD6, or Fulvestrant exhibits synergistic effects. TAT-PiET or TAT-PiET-PROTAC treatment overcomes endocrine therapy resistance in ERα-positive breast cancer cells. Taken together, we demonstrated that targeting the ET domain is effective in suppressing breast cancer, providing a therapeutic avenue in the clinic.

Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.

Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that protein disulfide isomerase (PDI) is an important mediator of chemically induced ferroptosis and also a new target for protection against ferroptosis-associated cell death. In the present study, we identified that 4-hydroxyestrone (4-OH-E1), a metabolic derivative of endogenous estrogen, is a potent small-molecule inhibitor of PDI, and can strongly protect against chemically induced ferroptotic cell death in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Pull-down and CETSA assays demonstrated that 4-OH-E1 can directly bind to PDI both in vitro and in intact cells. Computational modeling analysis revealed that 4-OH-E1 forms two hydrogen bonds with PDI His256, which is essential for its binding interaction and thus inhibition of PDI's catalytic activity. Additionally, PDI knockdown attenuates the protective effect of 4-OH-E1 as well as cystamine (a known PDI inhibitor) against chemically induced ferroptosis in human breast cancer cells. Importantly, inhibition of PDI by 4-OH-E1 and cystamine or PDI knockdown by siRNAs each markedly reduces iNOS activity and NO accumulation, which has recently been demonstrated to play an important role in erastin-induced ferroptosis. In conclusion, this study demonstrates that 4-OH-E1 is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.

Crocin enhances the sensitivity to paclitaxel in human breast cancer cells by reducing BIRC5 expression.

Paclitaxel (PTX) is one of the first-line chemotherapeutic agents for treating breast cancer. However, PTX resistance remains a major hurdle in breast cancer therapy. Crocin, the main chemical constituent of saffron, shows anti-cancer activity against various types of cancer. However, the effect of crocin on the resistance of PTX in breast cancer is still unknown. CCK-8 and TUNEL assays were employed to detect cell viability and apoptosis, respectively. The targets of crocin were predicted using HERB database and the targets associated with breast cancer were acquired using GEPIA database. The Venn diagram was utilized to identify the common targets between crocin and breast cancer. Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) expression was detected by qRT-PCR and western blot analysis. The correlation between BIRC5 expression and survival was analyzed by Kaplan-Meier plotter and PrognoScan databases. Our data suggested that crocin aggravated PTX-induced decrease of viability and increase of apoptosis in MCF-7 and MCF-7/PTX cells. BIRC5 was identified as the target of crocin against breast cancer. Crocin inhibited BIRC5 expression in MCF-7 and MCF-7/PTX cells. BIRC5 is overexpressed in breast cancer tissues, as well as PTX-sensitive and PTX-resistant breast cancer cells. BIRC5 expression is related to the poor survival of patients with breast cancer. Depletion of BIRC5 strengthened PTX-induced viability reduction and promotion of apoptosis in MCF-7 and MCF-7/PTX cells. Moreover, BIRC5 overexpression reversed the inhibitory effect of crocin on PTX resistance in breast cancer cells. In conclusion, crocin enhanced the sensitivity of PTX in breast cancer cells partially through inhibiting BIRC5 expression.

[Chinese expert consensus on the management of clinical pathway and adverse events of trastuzumab deruxtecan (2024 edition)].

Trastuzumab deruxtecan (T-DXd) is one of the new generation antibody-drug conjugates (ADCs) targeting human epidermal growth factor receptor 2 (HER-2) with bystander effect. T-DXd can not only significantly improve the survival of HER-2-positive advanced breast cancer patients, but also enable advanced breast cancer patients with low HER-2 expression to benefit from HER-2-targeted therapy. T-DXd has been approved by the National Medical Products Administration (NMPA) for the treatment of HER-2-positive or HER-2-low breast cancer patients. It is foreseeable that T-DXd will be widely used in clinical practice in the future. However, T-DXd has also shown different safety characteristics compared to previous HER-2 targeted drugs in clinical trials. How to manage T-DXd adverse events more reasonably and fully utilize the efficacy of T-DXd is an urgent clinical problem. Based on the existing clinical evidence and guideline consensus, combined with clinical practice experience, the expert group finally reached the consensus of clinical care pathway and adverse reaction management of trastuzumab deruxtecan after many discussions. This consensus content includes the clinical use method of T-DXd, pre-treatment patient education, and management of common or noteworthy adverse events of T-DXd. The adverse events include infusion related adverse events, digestive system adverse events (nausea/vomiting, constipation, diarrhea, and decreased appetite), hematological adverse events (neutropenia, febrile neutropenia, anemia, thrombocytopenia), respiratory adverse events (interstitial lung disease/pneumonia), cardiovascular adverse events (decreased left ventricular ejection fraction), adverse events in liver function (elevated transaminases) and other common adverse events (alopecia, fatigue, etc). This consensus focuses on the prevention of adverse events, dose adjustment and treatment when adverse events occur, and recommendations for patients' lifestyle, aiming to improve clinicians' understanding of T-DXd and provide practical guidance for clinical oncologists on T-DXd clinical management.

[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].

We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer( invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).

[Key Points of Examination after Breast Augmentation and Our Clinic's Algorithm of Immediate Reconstruction Using Silicone Implant for Breast Cancer Patient after Breast Augmentation].

Recently, the cases of breast augmentation for cosmetic purposes are rapidly increasing, there are more opportunities to examine for patient with breast augmentation history than before. In some cases, breast cancer screening is difficult due to the effects of breast augmentation. At our clinic, even in cases diagnosed with breast cancer after breast augmentation, we actively perform immediate breast reconstruction using silicone implant. However, it is necessary to consider the condition and type of breast augmentation at the time of diagnosis and also treatment. We will share our algorithm for immediate breast reconstruction using silicone implant for breast cancer after augmentation mammaplasty.

Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

Factors affecting heterogeneity in breast cancer microenvironment: A narrative mini review.

Breast cancer (BC) heterogeneity is a key trait of BC tumors with crucial implications on tumorigenesis, diagnosis, and therapeutic modalities. It is influenced by tumor intrinsic features and by the tumor microenvironment (TME) composition of different intra-tumoral regions, which in turn affect cancer progression within patients. In this mini review, we will highlight the mechanisms that generate cancer heterogeneity in BC and how they affect the responses to cancer therapies.

Weight management personas of breast cancer patients undergoing chemotherapy in China: a multi-method study.

BACKGROUND: Mobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users' personal information and persona development for the design and implementation of mHealth interventions. METHODS: Sixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant's experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC. RESULTS: Four themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics. CONCLUSIONS: The selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.

siRNA treatment targeting integrin α11 overexpressed via EZH2-driven axis inhibits drug-resistant breast cancer progression.

BACKGROUND: Breast cancer, the most prevalent cancer in women worldwide, faces treatment challenges due to drug resistance, posing a serious threat to patient survival. The present study aimed to identify the key molecules that drive drug resistance and aggressiveness in breast cancer cells and validate them as therapeutic targets. METHODS: Transcriptome microarray and analysis using PANTHER pathway and StemChecker were performed to identify the most significantly expressed genes in tamoxifen-resistant and adriamycin-resistant MCF-7 breast cancer cells. Clinical relevance of the key genes was determined using Kaplan-Meier survival analyses on The Cancer Genome Atlas dataset of breast cancer patients. Gene overexpression/knockdown, spheroid formation, flow cytometric analysis, chromatin immunoprecipitation, immunocytochemistry, wound healing/transwell migration assays, and cancer stem cell transcription factor activation profiling array were used to elucidate the regulatory mechanism of integrin α11 expression. Tumour-bearing xenograft models were used to demonstrate integrin α11 is a potential therapeutic target. RESULTS: Integrin α11 was consistently upregulated in drug-resistant breast cancer cells, and its silencing inhibited cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) while restoring sensitivity to anticancer drugs. HIF1α, GLI-1, and EZH2 contributed the most to the regulation of integrin α11 and EZH2 expression, with EZH2 being more necessary for EZH2 autoinduction than HIF1α and GLI-1. Additionally, unlike HIF1α or EZH2, GLI-1 was the sole transcription factor activated by integrin-linked focal adhesion kinase, indicating GLI-1 as a key driver of the EZH2-integrin α11 axis operating for cancer stem cell survival and EMT. Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset also revealed both EZH2 and integrin α11 could be strong prognostic factors of relapse-free and overall survival in breast cancer patients. However, the superior efficacy of integrin α11 siRNA therapy over EZH2 siRNA treatment was demonstrated by enhanced inhibition of tumour growth and prolonged survival in murine models bearing tumours. CONCLUSION: Our findings elucidate that integrin α11 is upregulated by EZH2, forming a positive feedback circuit involving FAK-GLI-1 and contributing to drug resistance, cancer stem cell survival and EMT. Taken together, the results suggest integrin α11 as a promising prognostic marker and a powerful therapeutic target for drug-resistant breast cancer.

Margin assessment during breast conserving surgery using diffuse reflectance spectroscopy.

Significance: During breast-conserving surgeries, it is essential to evaluate the resection margins (edges of breast specimen) to determine whether the tumor has been removed completely. In current surgical practice, there are no methods available to aid in accurate real-time margin evaluation. Aim: In this study, we investigated the diagnostic accuracy of diffuse reflectance spectroscopy (DRS) combined with tissue classification models in discriminating tumorous tissue from healthy tissue up to 2 mm in depth on the actual resection margin of in vivo breast tissue. Approach: We collected an extensive dataset of DRS measurements on ex vivo breast tissue and in vivo breast tissue, which we used to develop different classification models for tissue classification. Next, these models were used in vivo to evaluate the performance of DRS for tissue discrimination during breast conserving surgery. We investigated which training strategy yielded optimum results for the classification model with the highest performance. Results: We achieved a Matthews correlation coefficient of 0.76, a sensitivity of 96.7% (95% CI 95.6% to 98.2%), a specificity of 90.6% (95% CI 86.3% to 97.9%) and an area under the curve of 0.98 by training the optimum model on a combination of ex vivo and in vivo DRS data. Conclusions: DRS allows real-time margin assessment with a high sensitivity and specificity during breast-conserving surgeries.

Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy.

Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity.Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing adverse effects, highlighting the pivotal role played by FerOX in mitigating DOX-induced toxicity towards T-cells, thereby positioning it as a promising DOX formulation. This study contributes valuable insights to modern cancer therapy and immunomodulation.

The Effect of Melatonin on Increasing the Health Related Quality of Life in Non-Metastatic Breast Cancer Patients: Three-Year Follow up a Clinical Trial.

INTRODUCTION: Although breast cancer is common worldwide, if diagnosed early and treated on time, the probability of recovery is high and patients often experience a long life. Reducing the quality of life is a common side effect in patients. Melatonin may have an important role in fatigue, sleep disorders and, as a result, the health-related quality of life (HRQoL) in people. About 184 patients with breast cancer were enrolled in 2 groups: intervention with daily melatonin intake of 18 mg for 3 years (93 patients) and the control group with placebo intake (91 patients). Health-related quality of life and the effect of melatonin on increasing that were evaluated with the EORTC QLQ-C30 questionnaire, third edition at the beginning, 2 months later and 3 years after the beginning of the study. RESULTS: The general score of the HRQoL was significantly different both in the passage of time and in the comparative study of the 2 groups, and it was better in the melatonin group (P < .05). CONCLUSION: Long-term use of 18 mg of melatonin for 3 years in patients with non-metastatic breast cancer can lead to an increase in the patients' quality of life.

Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.

BACKGROUND: The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC. METHODS: We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies. RESULTS: A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61-0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75-0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76-0.96; P = 0.007). CONCLUSION: These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group.

Incidence of chemotherapy-related cardiac dysfunction in cancer patients.

BACKGROUND: Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. HYPOTHESIS: A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. METHODS: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. RESULTS: A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). CONCLUSION: Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.