Breast Cancer Patients Research Articles

Cost minimization analysis of treatments for metastatic HER2-positive breast cancer in Peru: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injections

The main objective of this study is to determine whether the employment of fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC; and Phesgo as brand name) to treat metastatic HER2-positive breast cancer patients would minimize costs compared to the traditional treatment of separate intravenous doses of pertuzumab and trastuzumab in Peru. To achieve this, we used EsSalud (the social security health insurance) data and assessed it through a mixed strategy, which consisted of a quantitative and a qualitative approach. The first one aimed to calculate the direct (non-drug consumables, drugs, and healthcare professionals) and indirect costs of both treatments to develop a comparison, whilst the second aimed to validate information and internalize the procedure in an EsSalud context. Overall, we found that the usage of PH FDC SC would be cost saving in EsSalud’s context. Specifically, we found three main advantages. Firstly, PH FDC SC generates a savings of 62% in non-drug consumables, which helps alleviate the healthcare system budget constraint. Secondly, its adoption frees up 61 hours of treatment and observation time for a single patient per year, which in turn increases the attention capacity of the healthcare system in terms of nursing hours and chemotherapy couches. Thirdly, the reduction of clinic time supposes an advantage for the patient in the form of increased productivity and well-being. Hence, the adoption of this drug would improve the quality of life of patients while reducing costs and pressure on the healthcare system. This is aligned with the strategy of prioritizing the appropriate breast cancer treatment within the National Cancer Care Plan. In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment.

High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype

BackgroundBreast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) and other immune regulation pathways in this neoplasia.MethodsIn this retrospective study, we evaluated the correlation of mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FOXO1 with clinicopathological factors and BC patient’s outcome by real-time quantitative polymerase chain reaction (qPCR).ResultsOur results showed that immunoregulatory gene expression depends on BC immunophenotype being CTLA-4 and PDCD1 (PD1) overexpressed on triple-negative/basal-like (TN/BL) and luminal B/HER2-positive phenotypes, respectively, and CD276 (B7-H3), JAK2 and FOXO1 associated with both luminal A and luminal B/HER2-negative tumors. In addition, we found that these genes can also be related to aggressive and non-aggressive clinicopathological characteristics in BC. Finally, survival analysis showed that CTLA-4 expression levels emerge as a significant independent factor of good prognosis in BC patients, especially in the HER2-enriched subtype.ConclusionConsidering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2-Overexpressing Breast Cancers

Abstract Background Human epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status. Methods Patients with stage I–III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed. Results Of 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65–4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12–3.71, p < 0.0001) pCR. Conclusion HER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.

Machine learning unveils key Redox signatures for enhanced breast Cancer therapy

BackgroundBreast cancer remains a leading cause of mortality among women worldwide, necessitating innovative prognostic models to enhance treatment strategies.MethodsOur study retrospectively enrolled 9,439 breast cancer patients from 12 independent datasets and single-cell data from 12 patients (64,308 cells). Moverover, 30 in-house clinical cohort were collected for validation. We employed a comprehensive approach by combining ten distinct machine learning algorithms across 108 different combinations to scrutinize 88 pre-existing signatures of breast cancer. To affirm the efficacy of our developed model, immunohistochemistry assays were performed. Additionally, we investigated various potential immunotherapeutic and chemotherapeutic interventions.ResultsThis study introduces an Artificial Intelligence-aided Redox Signature (AIARS) as a novel prognostic tool, leveraging machine learning to identify critical redox-related gene signatures in breast cancer. Our results demonstrate that AIARS significantly outperforms existing prognostic models in predicting breast cancer outcomes, offering a robust tool for personalized treatment planning. Validation through immunohistochemistry assays on samples from 30 patients corroborated our results, underscoring the model’s applicability on a wider scale. Furthermore, the analysis revealed that patients with low AIARS expression levels are more responsive to immunotherapy. Conversely, those exhibiting high AIARS were found to be more susceptible to certain chemotherapeutic agents, including vincristine.ConclusionsOur study underscores the importance of redox biology in breast cancer prognosis and introduces a powerful machine learning-based tool, the AIARS, for personalized treatment strategies. By providing a more nuanced understanding of the redox landscape in breast cancer, the AIARS paves the way for the development of redox-targeted therapies, promising to enhance patient outcomes significantly. Future work will focus on clinical validation and exploring the mechanistic roles of identified genes in cancer biology.

Characteristics of Breast Cancer Patients Who Refused Conventional Treatment in a Teaching Hospital in Southwestern Nigeria

Background Patients’ adherence to treatment recommendations is in the form of a spectrum: complete adherence or total rejection of the offered standard treatments. The aim of this study was to describe the characteristics of breast cancer patients who refused standard treatments in order to engender a focused intervention. Methods This was a retrospective study of breast cancer patients from 2017-2022. Data generated were analyzed using SPSS version 23.0. The results were presented using descriptive statistics. Inferential statistics for subgroup analysis was by chi-square test or risk difference with confidence intervals Results Among 343 patients, 86 (25% (95% CI 21-30) did not initiate conventional oncologic treatment. All were females and their age range was 33–83 years (mean, 49.9±12.0 years). The majority of the women were married (73%), educated (79%), low-income earners (69%), rural dwellers (63%) with advanced disease (81%). None of the patients had government insurance. The mean duration of symptoms was 11.9±9.7 months. Among 71patients with vital information, 50 (70% (95%CI 58-71) were confirmed dead in the last 3 years. The probability of death within 3 years was 38% (95%CI 8.0-68%) and was higher among those diagnosed as late-stage disease. Conclusions A large number of patients still fail to accept conventional treatments after breast cancer diagnosis. Understanding the patients’ characteristics may be necessary to recognize situations where active education and support can help patients accept standard treatment thereby prolonging survival.

Fatigue trajectories by wearable remote monitoring of breast cancer patients during radiotherapy

The aim of this pilot study was to assess the compliance of breast cancer (BC) patients with fitness tracker (FT) monitoring program during radiotherapy (RT) and to characterize radiation-induced fatigue (RIF) status through objective evaluation using FT-collected parameters. Thirty-six BC patients were invited to wear FT during their RT course for continuous monitoring of heart rate (HR) and step counts (STP). RIF assessment was performed weekly, according to CTCAE v5.0 and dichotomized into G0 vs. any-grade. A novel concept based on patient Repeated Activity Window (RAW) was introduced to evaluate HR and STP variations during RT. Several Machine Learning (ML) methods were trained to characterize RIF on the basis of HR and STP collected data. RIF of any grade was reported by 17 out of 36 patients (47%) included in the study. None of patient clinical variables were significantly correlated with RIF. All patients accepted the FT monitoring program, and for 32 patients FT collection efficiency was greater than 60%. For each patient, a distinct distribution of RAWs was identifiable over RT and across the entire patient cohort, with a total of 7950 RAWs processed. Six features related to RAWs, HR and STP were identified as associated with RIF. The best-performing classifier was the Bagged Trees model, showing a cross-validated ROC-AUC of 89% (95% CI 88–90%). This study confirms the feasibility of continuous biomedical monitoring of BC patients by FT. We successfully identify objective indicators of RIF through HR and STP variation measures within each patient’s RAW, thus providing a novel and practical approach to assess and manage RIF. This can significantly aid medical staff in evaluating RIF trajectories, potentially leading to better individualized care strategies and improved patient outcomes.

FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis.

A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in murine macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cell lines, which promotes cancer cell migration in vitro and metastasis in vivo. Notably, a deficiency of FABP4 in murine macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer.

FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis

A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in murine macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cell lines, which promotes cancer cell migration in vitro and metastasis in vivo. Notably, a deficiency of FABP4 in murine macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer.

Efficacy of Mammographic Artificial Intelligence-Based Computer-Aided Detection in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy

This study evaluates the potential of an AI-based computer-aided detection (AI-CAD) system in digital mammography for predicting pathologic complete response (pCR) in breast cancer patients after neoadjuvant chemotherapy (NAC). A retrospective analysis of 132 patients who underwent NAC and surgery between January 2020 and December 2022 was performed. Pre- and post-NAC mammograms were analyzed using conventional CAD and AI-CAD systems, with negative exams defined by the absence of marked abnormalities. Two radiologists reviewed mammography, ultrasound, MRI, and diffusion-weighted imaging (DWI). Concordance rates between CAD and AI-CAD were calculated, and the diagnostic performance, including the area under the receiver operating characteristics curve (AUC), was assessed. The pre-NAC concordance rates were 90.9% for CAD and 97% for AI-CAD, while post-NAC rates were 88.6% for CAD and 89.4% for AI-CAD. The MRI had the highest diagnostic performance for pCR prediction, with AI-CAD performing comparably to other modalities. Univariate analysis identified significant predictors of pCR, including AI-CAD, mammography, ultrasound, MRI, histologic grade, ER, PR, HER2, and Ki-67. In multivariable analysis, negative MRI, histologic grade 3, and HER2 positivity remained significant predictors. In conclusion, this study demonstrates that AI-CAD in digital mammography shows the potential to examine the pCR of breast cancer patients following NAC.

Low-dose apatinib in combination with chemotherapy for hormone receptor-positive, HER2-negative breast cancer with pulmonary lymphangitic carcinomatosis: A case report

Rationale: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by pulmonary lymphangitic carcinomatosis (PLC) poses significant therapeutic challenges due to the lack of standardized treatment protocols. Despite various therapeutic interventions and supportive care, prognosis remains dismal. Patient concerns: Herein, a 48-year-old Chinese woman presented with a persistent cough, unresponsive to anti-infective treatment for 1 month. A computed tomography (CT) scan revealed lymphatic vessel infiltration and a diffuse nodular pattern, suggestive of PLC. Diagnoses: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by PLC. Interventions: The patient was treated with a regimen comprising low-dose apatinib, capecitabine, and albumin-bound paclitaxel. Outcomes: The patient achieved a partial response, with a progression-free survival exceeding beyond ten months. Symptoms of dyspnea and dry cough significantly improved, alongside a notable reduction in lymphangitic carcinomatosis. Lessons: This case highlights the potential antitumor activity of apatinib in breast cancer patients with presenting with PLC. While further studies are necessary, this therapeutic approach could represent a viable option for managing breast cancer in the context of a visceral crisis. The case also emphasizes the importance of individualized treatment strategies and further research to substantiate these promising findings.

The intervention effect of psychological care combined with ondansetron, dexamethasone, and promethazine hydrochloride on chemotherapy in breast cancer surgical patients

BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women and imposes a significant health burden globally. According to data from the World Health Organization, the incidence of BC has been increasing steadily over the years. It has become one of the leading causes of cancer-related death among women worldwide. OBJECTIVE: This work was to evaluate the combined intervention effect of psychological care along with the use of ondansetron, dexamethasone, and promethazine hydrochloride in breast cancer (BC) patients undergoing chemotherapy, including their impact on nausea and vomiting control, quality of life (QoL), and psychological status. METHODS: 64 BC patients undergoing chemotherapy were collected and randomly rolled into a control group (Group C) and an intervention group (Group I). Group C received ondansetron combined with routine psychological support and counseling therapy, while Group I received a combination of ondansetron, dexamethasone, promethazine hydrochloride, and psychological care therapy. Self-assessment scores for anxiety, QoL ratings, white blood cell counts, and incidence of adverse reactions were assessed and compared between the two groups. RESULTS: Group I showed better control of nausea and vomiting versus Group C (P< 0.05). Marked improvements were also observed in the self-rating anxiety scale (SAS) scores, white blood cell counts, and nursing satisfaction in Group I versus Group C (P< 0.05). Nevertheless, the two groups had no significant difference regarding QoL scores (P> 0.05). CONCLUSION: the combination of psychological care with ondansetron, dexamethasone, and promethazine hydrochloride effectively controls nausea and vomiting symptoms in BC patients undergoing chemotherapy and provides higher levels of clinical nursing satisfaction.

Web-based interventions for fear of cancer recurrence: A scoping review with a focus on suggestions for the development and evaluation of future interventions.

The objective of this scoping review is to provide an overview of the available evidence on the effectiveness of web-based interventions for fear of cancer recurrence (FCR) and a discussion of drawbacks and possible improvements for web-based interventions identified in the reviewed studies. These steps fulfil the aim of this review, which is to offer suggestions for developing future web-based interventions based on the reviewed studies. Five databases (PubMed, MEDLINE, EMBASE, SCOPUS and Web of Science) were searched. Original peer-reviewed articles, written in English, on web-based interventions for FCR were included for review. The data from the included studies was synthesised thematically. We included 34 papers reporting on 28 interventions. Most of the studies in the papers were quantitative and mixed quantitative studies with a qualitative element, e.g. an interview post-intervention. Interventions were most commonly trialled with women breast cancer patients. Top three countries where studies were conducted were USA, Australia and the Netherlands. The most common theoretical framework for interventions is cognitive behavioural therapy (CBT), followed by mindfulness-based and mixed CBT, mindfulness, acceptance and commitment therapy (ACT), relaxation approaches. FCR was the primary focus/measure in 19 Studies, in 9 studies FCR was a secondary/related outcome/measure. Overall, the evidence of efficacy of web-based interventions on FCR is mixed. The existing research suggests several key points for producing more robust evidence about the effectiveness of web-based interventions for FCR. First, the studies suggest that it is a priority to better define eligibility criteria to proactively include people with higher levels of FCR. Second, there is a need for longer-term follow-up and outcome measuring period. Third, research examining the reasons for dropout from web-based interventions for FCR is critical to improve the effectiveness of web-based interventions. Fourth, while web-based interventions do not involve the costs of transportation, traveling time, space, equipment, cleaning, and other expenses, further cost utility analyses should be performed. Finally, future studies should assess how intervention accessibility, adherence, and effectiveness can be improved across different intervention designs, varying from intensive synchronous individual therapist-assisted web-based programme to blended designs combining the advantages of face-to-face and internet-based elements, to entirely self-managed programmes. Developing and evaluating more accessible FCR treatments have been identified among top international FCR research priorities (Shaw et al. 2021). While there is some evidence that web-based interventions can be as effective as face-to-face interventions, currently there is a dearth of systematic data about the ways in which the web-based modality specifically can enhance supportive care for FCR. Developing knowledge about effective web-based interventions has implications for cancer survivors as they can be presented with more accessible, low-cost and low-burden options for managing fear of cancer recurrence.

Treatment sequences and survival outcomes in advanced HR + HER2- breast cancer patients: a real-world cohort.

Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes. Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment. 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment. In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

The association of preoperative serum free fatty acid levels with survival in breast cancer patients

Background and objectivesSerum free fatty acids (FFA) are associated with various types of cancer. However, the prognostic value of preoperative serum FFA levels and breast cancer (BC) remains unclear. This study aimed to elucidate the specific relationship between FFA levels and BC outcomes.MethodsA retrospective review was conducted on 4133 patients with BC admitted to Sun Yat-sen Memorial Hospital from January 2015 to October 2021. Preoperative serum FFA levels were detected by the enzymatic endpoint method. The relationship between serum FFA levels and clinical characteristics was analyzed based on FFA interquartile range. Restricted cubic splines and multivariate Cox regression analyses were used to assess the relationship between preoperative serum FFA levels and overall survival (OS) in patients with BC. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.ResultsAccording to the FFA interquartile range, FFA levels were significantly correlated with OS (years) (p < 0.001). Restricted cubic spline analysis might reveal a U-shaped relationship between preoperative serum FFA levels and OS, after adjusting for other variables. According to the cutoff points for FFAs, multivariate Cox regression analyses showed that patients with low FFA levels (≤ 250 µmol/L) had higher rates of all-cause mortality and cancer-specific mortality than those with high FFA levels (530–700 µmol/L) in the total population and patients with a BMI of 18.5–24.0 kg/m2. A trend was observed indicating that elevated FFA levels (≥ 715 µmol/L) were associated with worse prognosis; however, this association failed to reach statistical significance.ConclusionsThere might be a nonlinear U-shaped relationship between preoperative serum FFA levels and survival in breast cancer patients, with lower FFA levels associated with worse OS. The effect of elevated FFA levels on prognosis requires further investigation.

Effects of antipsychotic drugs during radiotherapy in breast cancer in South Korea: a retrospective cohort study

In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer.

Adipocytes reprogram the proteome of breast cancer cells in organotypic three-dimensional cell cultures.

While epidemiological evidence has long linked obesity with an increased risk of breast cancer, the intricate interactions between adipocytes and cancer cells within the tumor microenvironment remain largely uncharted territory. The use of organotypic three-dimensional (3D) cell cultures that more accurately mimic the spatial architecture of tumors represents an innovative approach to this complex issue. In the present study, we investigated the effects of adipocytes on the proteome of Hs578t breast cancer cells cultured in a 3D microenvironment. Using different treatments, we rigorously optimized the experimental conditions to induce the optimal differentiation of 3T3-L1 fibroblasts into mature adipocytes. Then, we grow the Hs578t cells in a simulated microenvironment using an on-top model for organotypic 3D cultures. Our data showed that cancer cells formed 3D stellate-like architectures when grown over an extracellular matrix proteins-enriched scaffold for 48h. Proteomic profiling using LC-MS/MS mass spectrometry of Hs578t cells grown in 3D conditions with or without the adipocyte-enriched culture discovered 916 unique proteins. Of these, 605 showed no significant changes in abundance, whereas 87 proteins were significantly upregulated and 224 downregulated after interaction with fat cells (p < 0.05, FC > 2.0). Bioinformatic analysis of upregulated proteins indicated that the most enriched GO terms and molecular functions were related to lipids transport, cell differentiation, hypoxia response, and cell junctions. In addition, several modulated proteins have been previously associated with breast cancer progression. Interestingly, lipid transport proteins, including PITPNM2, ATP2C1, ABCA12, HDLBP, and APOB, showed perturbations in their expression, which were also associated with low overall survival in breast cancer patients. Functional studies showed that the knockdown of apolipoprotein B (APOB) expression in Hs578t cells reduced the size of 3D cellular structures. Moreover, APOB-knocked cells cocultured with adipocytes for 48h exhibited a significant decrease of intracellular lipids, whereas an increase in the adipocytes was found. Our results indicate that the 3D microenvironment and the adipocytes crosstalk reprogram the proteome of breast cancer cells. These data help us understand the environmental effects in gene expression and contribute to discovering novel tumor proteins with potential intervention in breast cancer therapy.

Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions.

Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions.

Hormonal suppression in premenopausal patients with estrogen receptor-positive breast cancer: a randomized trial comparing monthly versus trimonthly GnRH analogs

Background: Currently the standard of care for premenopausal women with estrogen receptor-positive breast cancer is the combined use of a gonadotropin-releasing hormone (GnRH) analog with either tamoxifen or an aromatase inhibitor in patients at high risk for relapse or when it is deemed necessary to optimize ovarian function suppression. Monthly GnRH analogs have been used for years but, recently, longer-acting formulations have been gaining approval. Yet, there is still a gap of evidence regarding the use of longer-acting formulations; only a few studies exist that examine their efficacy in breast cancer and compare them to the monthly formulations. It is the investigators’ hypothesis that trimonthly injections, which are more convenient for the patient and ensure better compliance, are better suited for use in breast cancer patients and may induce equally effective estrogen suppression as the monthly injections. Aim: A comparison of trimonthly versus monthly GnRH analogs in eliciting ovarian function suppression in premenopausal patients with estrogen receptor-positive breast cancer. Methodology: This is a prospective randomized open-label trial involving 25 premenopausal patients that were randomized to receive either a monthly or a trimonthly GnRH analog. Estrogen (E2) levels, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured on day 0 and on week 12. Patients, also, completed a questionnaire regarding exhibiting amenorrhea and other side-effects of the analogs. Results: All patients (N=25; 100%) from both groups achieved ovarian function suppression according to the criteria set by the researchers, which are E2 levels &lt;30 pg/mL and amenorrhea. Both groups exhibited a statistically significant decrease (almost by 50%) in E2 levels by week 12 (monthly group: E2 levels’ decrease equal to -18.5 pg/mL, p=0.00293; trimonthly group: E2 levels’ decrease equal to -13.9 pg/mL, p=0.0002441). On the contrary, FSH and LH levels did not show a statistically significant difference in either group. Moreover, when the two groups were compared, there was no statistically significant difference in the variation of all hormone levels between day 0 and week 12. All patients developed amenorrhea. There were no statistically significant differences in the number of side-effects between the two groups, even though the trimonthly group had fewer (in absolute number) side-effects than the monthly. Conclusion: This study demonstrates that the trimonthly formulations of GnRH analogs are equally effective in eliciting ovarian function suppression and present a similar percentage of side-effects as the monthly formulations, with the added benefit that patients need not undergo monthly injections.

Statin prescription disparities in patients with breast cancer and diabetes for primary cardiovascular disease prevention

BackgroundThis brief report examines statin prescription trends for primary cardiovascular disease (CVD) prevention in breast cancer (BC) survivors with diabetes, a large population at particularly high CVD risk.MethodsA population-based, retrospective cohort study was conducted using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting diabetes who were diagnosed with stage 0–III primary BC between 2008 and 2017 without preexisting CVD. We assessed statin prescription rates over time and also examined differences in statin prescription rates according to patient sociodemographic characteristics. Using a multivariate logistic regression adjusted for sociodemographic and clinical variables, independent predictors of statin prescription were identified.ResultsOf 8,423 BC patients with diabetes without preexisting CVD, 5,698 (68%) had a statin prescription. Statin prescriptions increased over time (BC diagnosis year 2008–2009: 65%, 2010–2011: 67%, 2012–2013: 66%, 2014–2015: 69%, 2016–2017: 70%; p = 0.01) and differed by age (66–69: 66%, 70–74: 70%, 75–79: 69%, ≥80: 65%; p &amp;lt; 0.01) and race (White: 68%, Black: 62%, Latina: 66%, Other: 72%; p &amp;lt; 0.01). In a multivariate analysis, race (Black vs. White: OR 0.80, 95% CI: 0.68–0.95) remained a predictor of statin prescription.ConclusionIn older early-stage BC survivors, statin prescriptions increased over time and varied by age, race, and BC stage. These findings can potentially inform strategies to improve guideline-concordant statin prescriptions in a group at high risk for CVD and reduce disparities.

Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295h + HER2- breast cancer: a retrospective analysis.

HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed. Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups. Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.