Treatment Of Breast Cancer Research Articles

Medicinal Aspects of PTP 1B Inhibitors as Anti-Breast Cancer Agents: An Overview.

Protein tyrosine phosphatase 1B (PTP1B) has gained interest as a therapeutic target for type 2 diabetes and obesity. Besides metabolic signalling, PTP1B is a positive regulator of signalling pathways linked to ErbB2-induced breast tumorigenesis. Substantial evidence proves that its overexpression is involved in breast cancer, which suggests that selective PTP1B inhibition might be effective in breast cancer treatment. Therefore, huge research is being carried out on PTP1B inhibitors and their activity against breast cancer development. To date, only two PTP1B inhibitors, viz. ertiprotafib and trodusquemine, have entered clinical trials. The discovery of selective inhibitors of PTP1B could open a new avenue in breast cancer treatment. In this review, we provide an extensive overview on the involvement of PTP1B in breast cancer, its pathophysiology, with special attention on the discovery and development of various natural as well as synthetic PTP1B inhibitors. This study will provide significant information to the researchers developing PTP1B inhibitors for breast cancer treatment.

Changes In Health-related Fitness After Breast Cancer Treatment In The AMBER Cohort Study

Changes In Health-related Fitness After Breast Cancer Treatment In The AMBER Cohort Study

Previous Anthracycline Treatment For Breast Cancer Impairs Exercise-induced Improvement In Cardiorespiratory Fitness

Previous Anthracycline Treatment For Breast Cancer Impairs Exercise-induced Improvement In Cardiorespiratory Fitness

Alkaloids as Additional Weapons in the Fight against Breast Cancer: A Review.

Breast carcinoma is among the most frequent cancerous tumour in females around the globe. The major modalities now employed in the therapeutic management of breast cancer include surgeries, chemotherapy, and specialized medicines. Despite their potential to help individuals' problems, they are also associated with many negative impacts. As a result, natural products are increasingly regarded to be a preferable alternative. Alkaloids are essential biochemical substances that can be used to develop new drugs. Numerous alkaloids that originate from natural plants have been shown in vitro and in vivo to have anti-proliferation and anti-metastasis actions on different kinds of carcinoma. According to the data collected in this study, the utilization of alkaloids as anti-tumor medicines appears to be extremely potent; nevertheless, extensive studies and clinical trials are required before utilizing individual alkaloids. In this overview, we provide a detailed and vital exploration of pre-existing alkaloids possessing anti-tumor activities due to bioactive compounds. This study also includes an overview of synthesized analogues and pharmacological characteristics that will be beneficial to scientists working on alkaloids for medicinal purposes. In a recent survey of the literature, alkaloids are an important component of plantderived antitumor medicines that hold great potential for the future development of cancer therapy and preventive therapies. We have also discussed structural analysis relationship (SAR) studies. Moreover, it covers clinical trial medications and FDA-approved medicines from the last five years that will be useful in further research.

Synthesis, and In-silico Studies of Indole-chalcone Derivatives Targeting Estrogen Receptor Alpha (ER-α) for Breast Cancer.

Breast cancer is the prominent reason of death in women worldwide, and the cases are increasing day by day. There are many FDA-approved drugs for treating breast cancer. Due to drug resistance, and problems in selectivity, there is a need to develop more effective agents with few side effects. Indole derivatives have demonstrated significant pharmacological potential as anti-breast cancer agents. Further, chalcone derivatives incorporating heterocyclic scaffolds play a significant role in medicine. Indole-chalcone-based compounds offer the potential for improved biological activity and enhanced drug-like properties. It prompted us to explore the synthesis of Indole-Chalcone derivatives targeting estrogen receptor alpha (ER-α) to discover potent anti-breast cancer agents. To synthesize indole-chalcone derivatives and study their binding interactions for ER-α protein by molecular docking for breast cancer treatment. In this study, indole-chalcone derivatives have been synthesized using conventional heating. With the help of Schrodinger software, molecular interaction as well as ADME (Adsorption, Distribution, Metabolism, and Excretion) studies of the compounds were conducted. Among all the synthesized compounds, four compounds (1, 2, 3, and 4) showed better docking scores (-10.24 kcal/mol, -10.15 kcal/mol, -9.40 kcal/mol, -9.29 kcal/mol, respectively) than the standard tamoxifen (-8.43 kcal/mol). From In-silico studies, we can conclude that four compounds from the synthesized series fit into the active site of ER-α. ADME properties of synthesized derivatives were found in the acceptable range. In the future, these compounds can be further explored for biological activity.

Perception Of Benefits, Barriers, And Self-efficacy Towards Physical Activity Among Women Undergoing Breast Cancer Treatment In Puerto Rico

Perception Of Benefits, Barriers, And Self-efficacy Towards Physical Activity Among Women Undergoing Breast Cancer Treatment In Puerto Rico

Synergistic response of PEG coated manganese dioxide nanoparticles conjugated with doxorubicin for breast cancer treatment and MRI application

In this research work, we designed a smart biodegradable PEG-coated MnO2 nanoparticles conjugated with doxorubicin (PMnO2-Dox NPs) for dual chemo-photodynamic therapy and magnetic resonance imaging (MRI) application. This highly sensitive pH-responsive PMnO2-Dox NPs causes effective drug release under acidic pH environment. PMnO2-Dox NPs not only improves the efficacy of chemo-photodynamic therapy due to synergistic response as well as improved MRI imaging via boosting T1 MRI contrast. Manifold characterization techniques have been employed for materials investigation. Crystallography of PMnO2-Dox NPs were performed by using XRD analysis, which confirmed tetragonal crystal structure with an approximate crystallite size of 20–30 nm. Surface morphology was confirmed via SEM analysis, results indicated the spherical and asymmetric agglomerated nanocluster of PMnO2-Dox NPs. In in vitro bioassay, the anticancer activity of PMnO2-Dox NPs were tested against breast cancer (MCF-7) cell line using MTT test. Moreover, it can also inhibit the growth of primary and secondary cancers without light exposure. Results suggested that PMnO2-Dox NPs not only convenient for cancer treatment via combined chemo-photodynamic therapy but also address the way towards a comprehensive strategy for MRI application via bright contrast agent T1 after overcoming the problem of multidrug resistance (MDR) and synergistic response of therapeutic analysis.

MiR-519e-5p regulates malignant phenotype of breast cancer cells through binding to CTPS1

MiR-519e-5p and CTPS1 are aberrantly expressed in breast cancer (BC). However, the molecular mechanisms underlying tumorigenesis and development are unknown, and their potential as therapeutic targets needs to be explored. The molecular biology was explored through in vitro cellular experiments, tumor xenograft assay, and analysis of gene expression in human tissue and serum samples. We found that miR-519e-5p expression was much lower and CTPS1 expression was much higher in BC tissues and cells than in the normal tissues and cells. BC cells overexpressing miR-519e-5p or CTPS1 knockdown demonstrated decreased proliferation, migration, and invasion, whereas miR-519e-5p knockdown had the opposite effect. Further studies showed that there is a binding site between miR-519e-5p and CTPS1, leading to their interaction, CTPS1 overexpression and could partially reverse the inhibitory effects of miR-519e-5p overexpression on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). CTPS1 serum levels were higher in patients with BC, and these levels were associated with some highly correlated clinical indicators, including age, HER-2 index, and T and N staging. Overall, miR-519e-5p slows the proliferation, invasion, migration, and EMT of BC by binding to CTPS1. This study offers a new direction for BC treatment.

Abstract C019: Peripheral Absolute Lymphocyte Count and Breast Cancer Mortality among Racially Diverse Women

Abstract Background: Among patients with triple-negative breast cancer (TNBC), higher tumor infiltrating lymphocytes (TILs) are associated with increased overall mortality (OM) and breast cancer-specific mortality (BCSM). We previously found that low peripheral absolute lymphocyte count (ALC) is associated with increased OM and BCSM in a sample of mostly non-Hispanic White (NHW) patients with TNBC. Here, we investigated the association between low ALC and mortality (OM and BCSM) across different breast cancer subtypes and whether the association is potentially modified by race and ethnicity. Methods: We used the Oncoshare database, which links electronic medical records (EMRs) data to the California Cancer Registry (CCR), and assessed women diagnosed with stage I-III breast cancer between 2000-2017, who had at least one ALC measurement and treated at two healthcare systems in California. Patient and tumor characteristics were obtained from the CCR and laboratory testing from EMRs. Patients with metastatic disease and chemotherapy receipt after one year of diagnosis were excluded. Multivariable logistic models assessed factors associated with “low ALC” (<1 K/µL, ever vs. never). We applied Cox models to evaluate the association between “min ALC” (lowest ALC value after diagnosis) and OM and BCSM within each breast cancer subtype (Luminal A, HER2-enriched, and TNBC), and further explored the interaction between min ALC and race and ethnicity. All models adjusted for low absolute neutrophil count, demographics, and tumor features. Results: Among 10,750 women analyzed, the risk of “low ALC” was associated with TNBC vs Luminal A (odds ratio (OR) 1.22, p=0.0098), older age (OR 1.01 per year, p<0.001), higher grade (grade 3 vs. 1, OR 1.15, p=0.042), higher stage (stage III vs. I, OR 1.81, p<0.001), and public vs. private health insurance (OR 1.29, p<0.001). Cox models showed that higher min ALC was associated with lower OM across breast cancer subtypes (Luminal A: HR 0.37, HER2-enriched: HR 0.32, TNBC: HR 0.22; all p<0.001) and BCSM (Luminal A: HR 0.29, HER2-enriched: HR 0.23, TNBC: HR 0.19; all p<0.001). Interaction analysis showed that race and ethnicity modified the association between min ALC and OM (interaction-p <0.001) and BCSM (interaction-p < 0.001) in the overall cohort; compared to NHW women (HR 0.38, 95% confidence interval [0.34-0.43]), the association between min ALC and OM was stronger among Hispanic (HR 0.24, [0.18-0.33]), Asian (HR 0.19, [0.14-0.25]), and Black (HR 0.21, [0.13-0.35]) women. Similar results were observed for BCSM. Conclusions: Low peripheral ALC, a routinely measured clinical lab result, strongly predicts higher BCSM and OM across breast cancer subtypes, beyond TNBC. The association between min ALC and BCSM/OM was stronger among Black and Asian women vs. NHW women, suggesting that maintaining normal ALC during breast cancer treatment may reduce BCSM and OM, especially for women from racial and ethnic minoritized groups. Future research should investigate differences in ALC, immune response, and BCSM in diverse populations. Citation Format: Candice N. Thompson, Ingrid Luo, Mina Satoyoshi, Lidia Schapira, Esther M. John, Summer S. Han, Allison W. Kurian. Peripheral Absolute Lymphocyte Count and Breast Cancer Mortality among Racially Diverse Women [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C019.

Abstract B096: Patient, Provider, and Advocate Perspectives on Factors that Impact Participation of Black Women in Breast Cancer Clinical Trials

Abstract Background: Black women are more likely to present with advanced stage disease and to die following a breast cancer (BC) diagnosis compared with women from other racial and ethnic groups. This persistent health inequity is in part driven by underrepresentation in clinical trials (CTs), as well as structural and social drivers of health. Multi-level factors impact patients’ decision to enroll on a cancer CT. Objective: The goal of the FOR ME (Fostering Opportunities in Research through Messaging and Education) study is to develop, optimize, and test a narrative web-based video intervention for Black women diagnosed with BC to promote shared decision making and CT participation. Here, we report findings from the development phase, wherein we engaged Black women with BC, oncologists and CT office staff, and cancer advocates. Our objective was to identify cross-cutting and unique themes concerning barriers and motivating factors to CT participation, intervention priorities, and to understand lived experiences to enhance authenticity and to inform video content. Methods: Guided by community engaged research approaches, we used multiple qualitative methods, including story circles and 1:1 interviews. We used thematic analysis and inductive and deductive coding approaches. Data analysis for each group followed the same approach: we annotated a subset of transcripts, compiled the annotations into a preliminary codebook, and conducted inter-coder reliability to improve quality and refine the codebook. Finally, we used Dedoose to analyze quotations and code co-occurrences, application frequencies, and relationships. We examined cross-cutting and unique themes during data collection and analysis. Results: In total, 38 Black women with BC participated in interviews and story circles, ranging in age from 27-75 years (M=59, SD =12); about 27% were currently receiving BC treatment and 27% had prior CT participation. Oncologists (n=16) and CT office staff (n=4) reported having on average 11.6 and 9.5 years of CT experience, respectively). Finally, 15 cancer advocates completed interviews, of whom 73% identified as Black women; 87% reported that the organization they were involved with connected patients to or provided education about CTs. Several cross-cutting themes were identified, including: 1) Acknowledgement of time, financial, and logistical burdens of CT participation; 2) The impact that current and historical racism, discrimination and mistreatment has had on CT enrollment for Black BC patients; 3) A lack of accessible CT information poses significant challenges for health literacy; and 4) Positive provider relationships and communication are important facilitators to CT participation. Conclusion: To promote health equity and participation in CTs among Black women with BC, interventions should consider multiple perspectives and prioritize addressing culturally sensitive patient-provider communication, shared decision-making, and patient empowerment. The information we learned will inform the development of a culturally tailored decision aid video. Citation Format: Leslie R. Carnahan, Eliza B. Cohn, Tigist Mersha, Neha Hippalgaonkar, Ryan Nguyen, Kauthar Salum, Ana Williams Waite, Christen Sandoval, Lolita Coleman, Beulah Brent, Paris Thomas, Paramjeet Khosla, Kent F. Hoskins, Vida Henderson. Patient, Provider, and Advocate Perspectives on Factors that Impact Participation of Black Women in Breast Cancer Clinical Trials [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B096.

Abstract B087: Inflammation and breast cancer: Understanding the interplay and implications for prevention and treatment

Abstract Breast cancer continues to be a major global health issue, affecting millions and posing challenges for researchers and healthcare workers. Recent research has revealed the importance of inflammation in the development and progression of a variety of malignancies, including breast cancer. The aim of this study is to investigate the complex association between inflammation and breast cancer in order to improve treatment and preventative techniques. A mixed-methods approach was used, with both quantitative and qualitative studies. The study included 580 breast cancer patients and 2,573 control participants. Patient records, hospital databases, and publicly available datasets were all used as data sources. Statistical methods, including univariate and multivariate logistic regression models, were employed to discover breast cancer predictors associated with inflammation. Breast cancer growth is strongly linked to chronic inflammation and specific inflammatory markers (CRP, IL-6, and TNF-α). Breast cancer incidence is correlated with geographical, demographic, and lifestyle characteristics such as region, age, gender, race, education level, and overall health condition. Comorbidities like hypertension, diabetes, and arthritis, as well as BMI, smoking, and physical activity levels, all have a role in risk. Anti-inflammatory drugs and lifestyle changes show promise for lowering the risk of breast cancer and improving patient outcomes. The study reveals significant relationships between breast cancer incidence and a variety of demographic, lifestyle, and health-related variables. Chronic inflammation is important in the development of breast cancer; therefore, inflammatory indicators could be used as diagnostic or therapeutic tools. The study suggests that tailored anti-inflammatory medications and lifestyle changes could have a significant impact on breast cancer prevention and therapy. This study emphasizes the necessity of knowing the relationship between inflammation and breast cancer. The insights revealed can lead to novel methods for breast cancer management, stressing the importance of ongoing research to fully understand the connection between inflammation and breast cancer and to implement these discoveries in clinical practice. Citation Format: Opeyemi O. Ogungbola, Samuel O. Ejeh, Jane Odeh, Olajumoke R. Omoniyi, Abayomi A. Akomolafe, Emmanuel K. Abudu. Inflammation and breast cancer: Understanding the interplay and implications for prevention and treatment [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B087.

A Complete Appraisal of Polymeric Micelle-Based Nanocarrier for Targeting Breast Cancer: Recent Strategies and Advancements

Aim/Objective: Polymeric micelle-based drug delivery systems have emerged as a beacon of hope in the challenging landscape of breast cancer therapy. This review aimed to explore the recent advancements and promising developments in the field, offering an in-depth analysis of their potential and challenges. The significance of this study lies in providing a comprehensive examination of the current advances in polymeric micelles technology, which have the potential to improve the efficiency and specificity of breast cancer therapy while minimizing adverse events. Methods: Polymeric micelles offer a revolutionary therapy by encapsulating therapeutic agents, allowing for controlled drug release and the precise targeting of malignant cells, while lowering systemic toxicity. Recent advances have focused on enhancing targeting strategies, including active and passive targeting, to increase the specificity of polymeric micelle-based therapies. A systematic review of literature was carried out using databases, like PubMed, Scopus, and Web of Science, which included papers published between 2010 and 2023. The selection criteria of the literature focused on the drug-loading capabilities and targeting strategies of the polymeric micelles, which could be advantageous for breast cancer treatment. Results: Clinical drug approaches leverage the versatility of micelles to co-deliver multiple agents, addressing the multifaceted nature of breast tumors and combating drug resistance. Additionally, polymeric micelles are finding applications in breast cancer diagnostics and imaging, enabling early detection and precise monitoring. The journey of polymeric micelle-based breast cancer therapy extends to formulation and engineering, preclinical and clinical studies, and confronts regulatory and commercialization challenges. However, the horizon is illuminated by emerging technologies, like personalized medicine, biomarker-driven targeting, and integration with novel therapies, promising a future where breast cancer treatment is tailored to individual patients and marked by improved efficacy and reduced side effects. Conclusion: In conclusion, this review underscores the transformative potential of polymeric micelle- based delivery systems in breast cancer therapy.

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study

Purpose Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005–2013. Methods Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%. Results Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Conclusions Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

Investigating the Salience of Clinical Meaningfulness and Clinically Meaningful Outcomes in Metastatic Breast Cancer Care Delivery

PURPOSE As metastatic breast cancer (mBC) treatment evolves, there is a need to understand how clinical meaningfulness, or a meaningful change in a patient's daily life, and clinically meaningful outcomes inform patient-centered care. Partnering with key stakeholders ensures patient-centered research incorporates the knowledge and expertise of advisors with lived experience. We describe a multistakeholder engagement approach to examine how people living with mBC (PLWmBC), caregivers, and health care providers interpret clinical meaningfulness and clinically meaningful outcomes and their influence on mBC treatment decision making and care. METHODS Qualitative focus groups with PLWmBC, caregivers, and health care providers were conducted and analyzed along three overarching themes: interpretations of clinical meaningfulness and clinically meaningful outcomes; treatment recommendations, preferences, and decisions; and implications for clinical practice. Patient-led and professional organizations served as research partners in study design, implementation, and interpretation of findings. RESULTS Partnerships were established with four patient-led and three professional organizations representing diverse constituencies throughout the United States. Twenty-two focus groups were conducted with 50 PLWmBC, 24 caregivers, and 41 health care providers (oncologists, n = 11; advanced practice providers, n = 13; oncology nurses, n = 17) between March and June 2023. PLWmBC and caregivers were unfamiliar with the concepts of clinical meaningfulness and clinically meaningful outcomes. Although health care providers were familiar, they did not use the terms when discussing treatment with PLWmBC. Across groups, participants emphasized the importance of meaningful outcomes beyond overall survival, including quality of life and improvement in symptoms and functioning. Participants noted that outcomes considered meaningful are individualized and dynamic. CONCLUSION This study offers insight into how partnering with patient advocacy and professional organizations can enhance research quality and aid translation of findings to clinical practice, thereby supporting patient-centered care.

Effectiveness of combined targeted and hormonal therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer: A systematic review and meta-analysis of RCTs.

we aim to synthesize available evidence on the effectiveness of hormonal plus targeted therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer. We searched the following databases: Medline, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, and African Journal. Only studies that investigated the effectiveness of hormonal therapy combined with targeted therapy for HR+/HER2- advanced breast cancer treatment were included. The outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). A random-effect meta-analysis model was employed. Statistical analysis was performed using Comprehensive Meta-analysis version 3. 24 studies were included in the meta-analysis with an overall sample size of 7635. Median PFS, OS and ORR were found to be significantly increased in the combination group compared to hormonal monotherapy [SMD = 6.072 (95% CI = 3.785-8.360), p < 0.001], [SMD = 1.614 (95% CI = 0.139-3.089), p = 0.032] and [OR = 1.584 (CI 1.134-2.213), p = 0.007] respectively. Subgroup analysis showed a significant difference in PFS and ORR between patients who received "hormonal therapy + CDK4/6 inhibitors" vs hormonal therapy only [SMD = 6.015 (CI 3.069-8.960), p < 0.001], (OR = 1.828 (CI 1.030-3.243), p = 0.039] respectively. Compared with hormonal monotherapy, targeted plus hormonal therapy significantly improves PFS, OS and ORR in postmenopausal women with HR+/HER2- advanced breast cancer.

Amplitude do rastreio e diagnóstico do câncer de mama no estado do Piauí e o impacto da pandemia da COVID-19

Introduction: The COVID-19 pandemic has brought about a new epidemiological reality worldwide that is responsible for altering the entire dynamics of addressing health issues globally. Cancer management policies were directly impacted, potentially leading to a decline in early case detection and a consequent increase in morbidity and mortality among patients with cancer. Objective: To analyze the impacts of the pandemic on breast cancer screening measures in the state of Piauí. Method: This epidemiological study used secondary data provided by the Department of Health Information of the Brazilian Unified Health System regarding the performance of mammograms and breast cancer diagnoses in the state of Piauí between 2017 and 2021. Results: Between 2017 and 2019, an average of 39,165 mammograms were performed annually, compared with an average of 22,367 exams in each year between 2020 and 2021. The data presented in this study indicate a significant decrease in the number of exams performed, associated with a decline in the absolute number of diagnoses, as well as delayed diagnoses. Conclusions: The scenario described in this study suggests the possibility of developing an epidemiological emergency related to breast cancer, both due to the structural incapacity of the state of Piauí to provide adequate assistance to patients and the increasing observation of more advanced cases. Therefore, we highlight the need for intensified efforts to strengthen breast cancer management and early diagnosis strategies in the state of Piauí.

Utilizing Indigenous Flora in East Africa for Breast Cancer Treatment: An Overview

Background: Breast cancer is a significant global health challenge, contributing substantially to cancer- related deaths. Conventional treatment methods, including hormone therapy, chemotherapy, surgical interventions, and radiation, have long been utilized. However, these traditional treatments are often associated with serious side effects and drug resistance, limiting their efficacy. Aim: This review aims to explore the potential of medicinal plants used in breast cancer management in East Africa, focusing on their bioactive compounds and anticancer properties. Methods: A comprehensive literature search was conducted to examine the effectiveness of medicinal plants in treating breast cancer across Kenya, Ethiopia, Uganda, Tanzania, and Rwanda. Relevant studies published between 2003 and 2023 were identified using keywords related to breast cancer and medicinal plants. The search was performed across multiple databases, including Google Scholar, PubMed, Scopus, Web of Science Core Collection, and Science Direct. Results: Numerous natural compounds found in East African medicinal plants including Cymbopogon citratus (Lemongrass,) Tabebuia avellanedae, Prunus africana (African Cherry), Euclea divinorum, Berberis holstii, Withania somnifera (Ashwagandha, Curcuma longa (Turmeric), Garcinia mangostana (Mangosteen, Vitis vinifera (Grapevine), Eugenia jambolana (Java Plum), Moringa oleifera (Drumstick Tree), Camellia sinensis (Tea), Glycine max (Soybean), Catharanthus roseus, Madagascar Periwinkle), Rhus vulgaris (Wild Currant) exhibit significant anticancer properties. These compounds have demonstrated the ability to reduce breast cancer aggressiveness, inhibit cancer cell proliferation, and modulate cancer-related pathways. Current research focuses on these natural and dietary compounds to develop more effective strategies for treating breast cancer. Conclusion: The findings suggested that East African medicinal plants hold promise as complementary treatments for breast cancer, offering potential benefits such as affordability, cultural appropriateness, and sustainability. Further research into these plants and their bioactive compounds could revolutionize breast cancer treatment, improving survival rates and addressing the rising incidence of breast cancer-related fatalities. Other: The review underscores the importance of continued research, conservation, and the integration of ancient healing methods to fully harness the potential of East African flora in breast cancer management.

Safety profile of trastuzumab originator vs biosimilars: a systematic review and meta-analysis of randomized clinical trials.

In the last decade trastuzumab biosimilars became more and more frequent. Among their uses, from several years, they have been available in Europe for the treatment of HER2-positive metastatic breast cancer, as an alternative to Herceptin®. This meta-analysis aimed to analyze the available literature with particular focus on phase 3 randomized clinical trials (RCTs) comparing adverse events between trastuzumab biosimilar and originator. A systematic review was conducted in Pubmed and Scopus to include all phase 3 RCTs related to trastuzumab in patients with HER2-positive breast cancer and published up to July 31, 2023. Of the 508 records identified, 14 articles were meta-analyzed for safety information, including serious treatment emergent adverse events, death-related adverse events, neutropenia, leukopenia, infections, increased ALT, increased AST, anti-drug antibody, and neutralizing antibody. Included patients had an early breast cancer (N=2,877) or a metastatic breast cancer (N=2,603). No significant difference in death-related adverse events was found for trastuzumab biosimilar and originator when evaluated for an early breast cancer in the neoadjuvant phase (Risk Ratio [RR], 1.30; 95% confidence interval [CI], 0.47-3.59; I2 = 0%; p = 0.57) and overall (RR, 0.43; 95%CI, 0.11-1.66; I2 = 20%; p = 0.26), and for metastatic breast cancer (RR, 0.61; 95%CI, 0.30-1.26; I2 = 0%; p = 0.85). No difference was also observed for all other safety outcomes as in accordance with clinical studies necessary for the registration and approval of a biosimilar at a European level.

TCR-engineered T-cells directed against Ropporin-1 constitute a safe and effective treatment for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) shows an urgent need for new therapies. We discovered Ropporin-1 (ROPN1) as a target to treat TNBC with T-cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues. HLA-A2-binding peptides were detected via immunopeptidomics and predictions and used to retrieve T-cell receptors (TCRs) from naïve repertoires. Following gene introduction into T-cells and stringent selection, we retrieved a highly specific TCR directed against the epitope FLYTYIAKV that did not recognize non-cognate epitopes from alternative source proteins. Notably, this TCR mediated killing of three-dimensional tumoroids in vitro and tumor cells in vivo and outperformed standard-of-care drugs. Finally, the T-cell product expressing this TCR and manufactured using a clinical protocol fulfilled standard safety and efficacy assays. Collectively, we have identified and preclinically validated ROPN1 as a target and anti-ROPN1 TCR T-cells as a treatment for the vast majority of TNBC patients.

Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer

CoQ10 (Coenzyme Q10) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.