An Artificial Intelligence-Based Tool for Enhancing Pectoral Muscle Segmentation in Mammograms: Addressing Class Imbalance and Validation Challenges in Automated Breast Cancer Diagnosis.

Breast cancer remains a major health concern worldwide, requiring the advancement of early detection methods to improve prognosis and treatment outcomes. In this sense, mammography is regarded as the gold standard in breast cancer screening and early detection. However, in a scenario where extensive analysis is required, a large set of mammograms conducted by radiologists may carry out false negative or false positive diagnoses. Therefore, artificial intelligence has emerged in recent years as a method for enhancing timing in breast cancer diagnosis. Nonetheless, preprocessing stages are required to prepare the mammography dataset to enhance learning models to correctly identify breast anomalies. In this paper, we introduce a novel method employing convolutional neural networks (CNNs) to segment the pectoral muscle in 1288 mediolateral oblique mammograms (MLOs), thereby addressing class imbalance and overfitting between classes, and dataset augmentation based on translation, rotation, and scale transformation. The effectiveness of the model was assessed through a confusion matrix and performance metrics, highlighting an average Dice coefficient of 0.98 and a Jaccard index of 0.96. The outcomes demonstrate the model capability to accurately identify three classes: pectoral muscle, breast, and background. This study emphasizes the importance of tackling class imbalance problems and augmenting data for the training of models for reliable early breast cancer detection.

Non-coding RNAs as modulators of radioresponse in triple-negative breast cancer: a systematic review.

Triple-negative breast cancer (TNBC), characterized by high invasiveness, is associated with poor prognosis and elevated mortality rates. Despite the development of effective therapeutic targets for TNBC, systemic chemotherapy and radiotherapy (RdT) remain prevalent treatment modalities. One notable challenge of RdT is the acquisition of radioresistance, which poses a significant obstacle in achieving optimal treatment response. Compelling evidence implicates non-coding RNAs (ncRNAs), gene expression regulators, in the development of radioresistance. This systematic review focuses on describing the role, association, and/or involvement of ncRNAs in modulating radioresponse in TNBC. In adhrence to the PRISMA guidelines, an extensive and comprehensive search was conducted across four databases using carefully selected entry terms. Following the evaluation of the studies based on predefined inclusion and exclusion criteria, a refined selection of 37 original research articles published up to October 2023 was obtained. In total, 33 different ncRNAs, including lncRNAs, miRNAs, and circRNAs, were identified to be associated with radiation response impacting diverse molecular mechanisms, primarily the regulation of cell death and DNA damage repair. The findings highlighted in this review demonstrate the critical roles and the intricate network of ncRNAs that significantly modulates TNBC's responsiveness to radiation. The understanding of these underlying mechanisms offers potential for the early identification of non-responders and patients prone to radioresistance during RdT, ultimately improving TNBC survival outcomes.

Male and female disparities in breast cancer epidemiology: A comparative cross-sectional analysis of a Brazilian cohort (2017-2021).

Male breast cancer (MBC) is a rare condition, accounting for approximately 1 % of all breast cancer cases. Nevertheless, the paucity of MBC-specific research has impeded a thorough understanding of MBC. In this study, we aimed to delineate the epidemiological implications of MBC in Brazil and benchmarked it against female breast cancer (FBC). This retrospective study analyzed data from the DATASUS database (2017-2021), which assessed the incidence of breast cancer in both sexes. All statistical analyses were performed using descriptive statistics and inferential methods, with significance set at a 95 % confidence interval. We identified 4,326 (1.7 %) and 233,793 (94.2 %) patients with MBC and FBC, respectively, in Brazil. Despite the general population concentration in the Southeast, MBC cases were more prevalent in the Northeast (p < 0.0004). At breast cancer diagnosis, males were typically older (mean age 59.5 [±10.2] years) than females (mean age 55.7 7 [±9.8] years). MBC was more commonly diagnosed clinically compared with FBC, which was most commonly diagnosed via screening. Surgical diagnostics were twice as likely in males, who also more frequently presented with advanced disease stages (stages III and IV; 72.8 % vs. 59.3 %), leading to a higher rate of mastectomy. Treatment was initiated earlier in males than in females. Although MBC comprises a minority of breast cancer cases, it is more frequently diagnosed at an advanced stage compared with FBC and necessitates aggressive treatment. Our study also underscores the potential benefit of prompt initiation of therapy and need for tailored clinical approaches in patients with MBC.

Anti-Cancer Potential of Linear ß-(1→6)-D-Glucan from Agaricus bisporus on Estrogen Receptor-Positive (ER+) Breast Cancer Cells.

Mushroom ß-D-glucans can be isolated from several species, including the widely consumed Agaricus bisporus. Besides immunomodulatory responses, some ß-D-glucans may exhibit direct antitumoral effects. It was previously observed that a ß-(1→6)-D-glucan (BDG16) has indirect cytotoxicity on triple-negative breast cancer cells. In this study, the cytotoxicity of this same glucan was observed on estrogen receptor-positive (ER+) breast cancer cells (MCF-7). Cell viability was determined by multiple methods to assess metabolic activity, lysosomal membrane integrity, and adhesion capacity. Assays to evaluate cell respiration, cell cycle, apoptosis, necroptosis, and oxidative stress were performed to determine the action of BDG16 on MCF-7 cells. A gradual and significant cell viability reduction was observed when the cells were treated with BDG16 (10-1000 µg/mL). This result could be associated with the inhibition of the basal state respiration after incubation with the ß-D-glucan. The cells showed a significant arrest in G1 phase population at 1000 µg/mL, with no induction of apoptosis. However, an increase in necrosis and necroptosis at the same concentration was observed. No difference in oxidative stress-related molecules was observed. Altogether, our findings demonstrate that BDG16 directly induces toxicity in MCF-7 cells, primarily by impairing mitochondrial respiration and promoting necroptosis. The specific mechanisms that mediate this action are being investigated.

Solid Lipid Nanoparticles, an Alternative for the Treatment of Triple-Negative Breast Cancer.

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Cruciferous Plant Extracts, Their Isothyocianate or Indol Derivatives, and Their Effect on Cellular Viability of Breast Cancer Cell Lines.

Brassicaceaes are rich in glucosinolates (GSL), whose derivatives, the isothyocianates sulforaphane (SFN), iberine (IB), or indole derivatives as indole-3-carbinol (I3C), have anticancer activities. We evaluated the effects of a broccoli sprout (Brassica oleracea var italica) and red cabbage (B. oleracea L. var capitata f. rubra) extracts and their GSL derivatives on breast cancer cells. Broccoli sprout aqueous extract (BSE) and red cabbage aqueous (RCA) or ethanolic (RCE) extracts were high in SFN, IB, and/or I3C. BSE and RCA decreased proliferation at doses of 2.5-5 mg/mL but induced proliferation at lower doses. RCE decreased proliferation starting at 10 µg/mL with selectivity toward cancer cells. SFN, IB, or I3C alone or in combination did not decrease proliferation similarly, suggesting synergistic effects with other phytochemicals in the extract. RCE showed selectivity toward breast cancer cells, but the effect of the individual metabolites or their combination did not reduce proliferation to the same extent. It will be important to determine the combination responsible for this effect to characterize their use for breast cancer treatment.

Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer.

Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect in vitro of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between RETN and MAPK3 expression in basal triple-negative breast cancer. Importantly, we found amplifications of the RETN gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.

MicroRNA-1307-3p contributes to breast cancer progression through PRM2.

BACKGROUND: Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR-1307-3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR-1307-3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes. METHODS: Basal miR-1307-3p levels were quantified in BC cell lines MDA-MB-231 and MCF-7, as well as MCF-10A using quantitative real-time reverse transcription-PCR (RT-qPCR). The impact of miR-1307-3p inhibition on BC cell proliferation, migration, invasion, and angiogenesis was assessed. Nine miRNA-target prediction databases identified potential miR-1307-3p targets. Target expression was validated using RT-qPCR, Western blot, and dual-luciferase reporter assays. MiR-1307-3p was overexpressed in MDA-MB-231 and MCF-7 compared to MCF-10A. RESULTS: Inhibiting miR-1307-3p significantly reduced BC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis identified 17 potential miR-1307-3p targets, with protamine 2 (PRM2) overexpression confirmed via Western blot and dual-luciferase assays. CONCLUSION: MiR-1307-3p overexpression in BC promotes proliferation, migration, invasion, and angiogenesis. PRM2 emerges as a novel miR-1307-3p target in BC.

APX2009 sensitizes hypoxic breast cancer cells to doxorubicin by increasing its accumulation and caspase-3/7-mediated apoptosis.

PURPOSE: The association of targeted therapy with chemotherapy is encouraged to increase the treatment efficiency, especially in hypoxic triple-negative breast cancer. The APE1 redox activity has stood out as a potential tumor target. However, the effect of the association of the APE1 redox inhibitors with doxorubicin in hypoxia still needs to be evidenced. Therefore, our objective was to investigate the effect of the APX2009 (APE1 inhibitor) on the sensitization of breast cancer cells to doxorubicin in normoxia and hypoxia. METHODS: The WST-1 assay was used to evaluate cell viability after APX2009 and doxorubicin application under normoxia and hypoxia conditions in the MCF-7 and MDA-MB-231 cells. Apoptosis was analyzed by annexin assay and detection of caspases-3/7 activity by luminescence-based assay. The clinical association between APE1 inhibition signature and doxorubicin sensitivity was evaluated by bioinformatics analyses. RESULTS: MDA-MB-231 and MCF-7 cell lines were more sensitive to APX2009 in normoxia than in hypoxia. Co-treatment with APX2009 and doxorubicin in hypoxia further decreased the viability of triple-negative MDA-MB-231 cells than treatment alone, which was accompanied by doxorubicin intracellular accumulation, and increase of apoptotic cells percentage, and caspases-3/7 activity. Moderate association was found between APE1 inhibition signature and doxorubicin sensitivity in the hypoxic basal subtype. CONCLUSION: The findings suggest that APX2009 sensitizes the MDA-MB-231 cells to doxorubicin in hypoxia by doxorubicin intracellular accumulation and caspases-3/7-mediated apoptosis.

Development of a Second Primary Lung Cancer Following a Primary Breast Cancer: A Case Series.

Breast cancer (BC) accounts for 24.2% of all women's malignant tumors, with rising survival rates due to advancements in chemotherapy and targeted treatments. However, second primary cancers, particularly lung cancer (LC), have become more prevalent, often emerging approximately 10 years after BC treatment. This study presents a case series of 9 women diagnosed with second primary LC following BC, treated at a high-complexity hospital in Colombia between 2014 and 2019. All initial BCs were ductal carcinomas, 7 were triple negative, 1 was human epidermal growth factor receptor 2 positive, and 1 was estrogen and progesterone positive. Each patient had undergone radiation therapy, and 7 had received chemotherapy, increasing their LC risk. The second primary LCs, all adenocarcinomas, were confirmed using immunohistochemical stains for thyroid transcription factor-1 (TTF-1), Napsin A, and estrogen receptor (ER) status. The interval between treatments and LC detection ranged from 1 to 17 years, with 4 cases identified after 10 years and 3 within 1 to 3 years, underscoring the need for prolonged surveillance. Seven LCs were ipsilateral to the BC and radiation site, while 2 were contralateral, highlighting the necessity of monitoring both sides for potential LC development. This case series enhances the local epidemiological understanding, showing that prior radiotherapy for BC and histological analysis are key in characterizing second primary LC patients. The study emphasizes the critical role of accurate histological diagnosis in guiding treatment approaches for lung lesions in BC survivors.

Real-world evidence of survival outcomes in breast cancer subtypes after neoadjuvant chemotherapy in a Brazilian reference center.

BACKGROUND: Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes. METHODS: A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point. RESULTS: The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS. CONCLUSIONS: These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.

Improvement of quality of life on breast cancer-related lymphedema patients through a postmastectomy care program in Mexico: a prospective study.

PURPOSE: To assess whether health-related quality of life (HRQOL) improved through a postmastectomy care program focused on breast cancer-related lymphedema (BCRL) protection/awareness. METHODS: Postoperative breast cancer patients were enrolled prospectively (February-2018 to September-2019) at Nursing and Obstetrics Faculty, Durango, Mexico. Sociodemographic/clinical characteristics, arm measurements, and HRQOL evaluation with Functional Assessment Cancer Therapy-Breast Cancer were collected at baseline and after six follow-up assessments between six-to-twelve-month postmastectomy. Lymphedema was verified through circometry. Descriptive analysis and McNemar-Bowker test were used to evaluate paired differences in HRQOL. Subgroup analysis was conducted to assess sociodemographic/clinical characteristics of BCRL using Pearson's chi-squared or Fisher exact test along with odds ratios (OR) and 95% confidence intervals (CI). All tests were two-sided with P-values < 0.05 considered statistically significant. RESULTS: One-hundred-two patients developed BCRL (incidence 66.2%, n = 154). All dimensions of HRQOL improved after the postmastectomy care program (P < 0.05). The subgroup analysis indicated that elementary academic degree (OR = 2.40, 95%CI: 1.01-5.69), laborer (OR = 9.85, 95%CI: 3.30-29.3), and total mastectomy (OR = 4.23, 95%CI: 1.20-14.9) were more associated with BCRL (P < 0.05). Conversely, high school academic degree (OR = 0.46, 95%CI: 0.22-0.94), married status (OR = 0.42, 95%CI: 0.21-0.86), housewife (OR = 0.27, 95%CI: 0.12-0.61), professional occupation (OR = 0.10, 95%CI: 0.01-0.64), and having no comorbidities (OR = 0.31, 95%CI: 0.15-0.63) were less associated with BCRL (P < 0.05). CONCLUSION: Although HRQOL improved through the postmastectomy care program, our findings suggest that lower education, working as a laborer, and total mastectomy may be more associated with BCRL. Continuing research may uncover liabilities among BCRL patients within limited-resources settings.

Physical exercise in Chilean breast cancer survivors: Qualitative study of barriers, facilitators and preferences. / Actividad física en chilenas sobrevivientes de cáncer de mama: estudio cualitativo de barreras, facilitadores y preferencias.

Introduction: Breast cancer survivors often experience pre and post-treatment physical and psychological symptoms, negatively affecting their quality of life. Regular physical exercise is associated with better quality of life and lower recurrence of cancer, and therefore all oncological patients are recommended to practice it in a regular basis. Despite this, breast cancer survivors have low adherence to physical exercise. The purpose of this study is to identify barriers, facilitators and preferences of Chilean breast cancer survivors to practice physical exercise. Methods: Phenomenological qualitative study of 12 in-depth interviews with adjuvant radiation therapy concluded at least three months ago. Results: Breast cancer survivors ignored the benefits of physical exercise during and after treatment. The barriers were physical symptoms, psychological barriers, sociocultural barriers, health system barriers, disinformation and sedentary lifestyle. Facilitators were coping with physical symoptoms, psychological issues, having information and active lifestyle. The preferences were painless and familiar exercises. Preferred exercise was walking. Conclusions: Breast cancer survivors may adhere to physical exercise despite barriers when certain facilitators are present, which may be promoted by the health team when reporting the benefits of the physical exercise, prescribing personalized, safe and painless physical exercise and educating both patient and her family about the role of the physical exercise in cancer recovering process.

Introducción: Las sobrevivientes de cáncer de mama suelen ver afectada negativamente su calidad de vida por síntomas físicos y psicológicos pre y post tratamiento. La práctica regular de ejercicio físico se asocia a mejor calidad de vida y menor recurrencia del cáncer, por esto es recomendado a todos los pacientes oncológicos. Sin embargo, existe baja adherencia a este. El propósito de este artículo es identificar barreras, facilitadores y preferencias de sobrevivientes de cáncer de mama chilenas para realizar ejercicio físico. Métodos: Estudio cualitativo fenomenológico, basado en entrevistas en profundidad a 12 sobrevivientes de cáncer de mama que terminaron la radioterapia adyuvante hace tres o más meses. Resultados: Las sobrevivientes de cáncer de mama desconocían la importancia del ejercicio físico durante y después del tratamiento. Las barreras identificadas fueron síntomas físicos, barreras psicológicas, socioculturales, del sistema de salud; desinformación y sedentarismo. Los facilitadores fueron físicos, psicológicos, contar con información y práctica de ejercicio físico antes del diagnóstico. Las preferencias fueron ejercicios indoloros y familiares. El ejercicio preferido fue caminar. Conclusiones: Es posible que las sobrevivientes de cáncer de mama adhieran al ejercicio físico, a pesar de las barreras cuando hay ciertos facilitadores presentes. Estos pueden ser generados por el equipo médico al informar los beneficios del ejercicio físico, prescribir ejercicio físico personalizado, seguro e indoloro y educar a la paciente y a su familia sobre el rol del ejercicio físico en la recuperación de sobrevivientes de cáncer de mama.

Deciphering the causes of advanced-stage disease at diagnosis among breast cancer patients who attended a suburban hospital in Buenos Aires.

INTRODUCTION: Breast cancer is still one of the main causes of cancer mortality in women worldwide, and death rates are even greater in vulnerable populations. A delay in diagnosis usually comes with advanced-stage disease, which impacts patient survival. The aim of this study was to evaluate the time for first medical consultation among women with breast cancer attending the Magdalena V. de Martínez Hospital and to determine the causes that may influence patient delay and its impact on cancer stage at diagnosis. MATERIALS AND METHODS: Three hundred and six breast cancer patients were interviewed using a self-report questionnaire, and socioeconomic and demographic variables, namely, highest education level completed, employment status and breast cancer awareness, were collected. The answers were associated with patient clinical records, such as clinical staging and tumor size. RESULTS: Forty-nine percent of the patients were diagnosed with advanced-stage disease. These women had either a deficiency in breast cancer awareness, did not visit a gynecologist after age 40 or, were unemployed, while those patients diagnosed with early-stage breast cancer had nonpalpable tumors, declared a sufficient household income or delayed less than four weeks in seeking medical attention. Moreover, the delay in the first medical visit was more than one month in 78% of the patients, being disregard the most common cause of postponement. Additionally, patient delays were associated with larger tumors and with incomplete education. DISCUSSION: These results indicate that early detection efforts should be made to reduce the disease stage at diagnosis, which may impact on overall survival.

Introducción: El cáncer de mama (CM) es una de las principales causas de mortalidad por cáncer en mujeres, y las tasas de mortalidad son aún mayores en poblaciones vulnerables. Un retraso en el diagnóstico suele acompañarse con estadios avanzados de la enfermedad, lo que impacta en la supervivencia del paciente. El objetivo fue evaluar el tiempo transcurrido para la primera consulta médica entre mujeres con CM que asisten al Hospital Magdalena V. de Martínez y determinar las causas que pueden influir en la demora del paciente y su impacto en el estadio al momento del diagnóstico. Materiales y métodos: Se entrevistaron 306 pacientes con CM utilizando un cuestionario autoinformado, y se recopilaron variables socioeconómicas y demográficas, entre ellas, nivel educativo más alto completado, situación laboral y conocimiento sobre el CM. Las respuestas se asociaron con los registros clínicos de las pacientes. Resultados: El 49% de las pacientes fueron diagnosticadas con enfermedad en estadios avanzados. Estas mujeres tenían deficiencias en el conocimiento sobre el CM, no consultó al ginecólogo después de los 40 años o estaba desempleada, mientras que aquellas diagnosticadas con CM en estadios tempranos tenían tumores no palpables, declaraban un ingreso familiar suficiente o demoraban menos de cuatro semanas en buscar atención médica. Además, la demora en la primera visita médica fue de más de un mes en el 78% de las pacientes, siendo el desinterés la causa más común de postergación. Asimismo, las demoras estaban asociadas con tumores más grandes y con una educación incompleta. Discusión: Este estudio sugiere la necesidad de desarrollar estrategias de sensibilización y educación sobre el CM, así como de políticas para mejorar el acceso a la atención médica, especialmente para poblaciones vulnerables, con el fin de reducir el retraso en el diagnóstico y mejorar la salud de las pacientes con CM.

Mucinous Carcinoma in a Male: First Documented Case in Nicaragua.

Breast malignancy in men is an exceedingly rare condition, representing a small fraction of all diagnosed breast cancer cases. The most common histological subtype is invasive ductal carcinoma, while the mucinous type is extremely rare. This pathology has a high mortality rate due to its poor prognosis and diagnosis in advanced stages, often initially overlooked with limited screening. Surprisingly, more men have died from breast cancer than from testicular cancer. This report details a case of invasive mucinous carcinoma in a 75-year-old male who presented with a five-week history of chronic non-productive cough and signs of pleural effusion. A breast magnetic resonance imaging (MRI) revealed a retroareolar breast tumor, and a second-look ultrasound confirmed the presence of a BI-RADS 4C solid nodule. Histopathological and immunohistochemical results were confirmed by ultrasound-guided tru-cut biopsy, identifying invasive mucinous carcinoma and luminal B (HER2+) subtype. Staging studies were negative for metastasis, and a modified radical mastectomy was performed, yielding favorable intraoperative findings. The incidental diagnosis in this patient highlights the necessity of comprehensive imaging in atypical presentations. Despite its rarity, awareness and early detection of mucinous carcinoma are essential for optimizing patient outcomes. This case also underscores the disparity in breast cancer outcomes between low gross domestic product (GDP) and high-GDP countries, emphasizing the need for improved access to diagnostic and therapeutic resources. Enhanced clinical awareness and early detection are crucial for improving outcomes in patients with rare histological subtypes, particularly in underserved regions.

Overall glycaemic index and dietary glycaemic load and all-cause and cause-specific mortality in women from the Mexican Teachers' Cohort.

Previous studies have found direct associations between glycaemic index (GI) and glycaemic load (GL) with chronic diseases. However, this evidence has not been consistent in relation to mortality, and most data regarding this association come from high-income and low-carbohydrate-intake populations. The aim of this study was to evaluate the association between the overall GI and dietary GL and all-cause mortality, CVD and breast cancer mortality in Mexico. Participants from the Mexican Teachers' Cohort (MTC) study in 2006-2008 were followed for a median of 10 years. Overall GI and dietary GL were calculated from a validated FFQ. Deaths were identified by the cross-linkage of MTC participants with two national mortality registries. Cox proportional hazard models were used to estimate the impact of GI and GL on mortality. We identified 1198 deaths. Comparing the lowest and highest quintile, dietary GI and GL appeared to be marginally associated with all-cause mortality; GI, 1·12 (95 % CI: 0·93, 1·35); GL, 1·12 (95 % CI: 0·87, 1·44). Higher GI and GL were associated with increased risk of CVD mortality, GI, 1·30 (95 % CI: 0·82, 2·08); GL, 1·64 (95 % CI: 0·87, 3·07) and with greater risk of breast cancer mortality; GI, 2·13 (95 % CI: 1·12, 4·06); GL, 2·43 (95 % CI: 0·90, 6·59). It is necessary to continue the improvement of carbohydrate quality indicators to better guide consumer choices and to lead the Mexican population to limit excessive intake of low-quality carbohydrate foods.

In-Depth Analysis of the Peripheral Immune Profile of HER2+ Breast Cancer Patients on Neoadjuvant Treatment with Chemotherapy Plus Trastuzumab Plus Pertuzumab.

Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

AI-assisted models to predict chemotherapy drugs modified with C60 fullerene derivatives.

Employing quantitative structure-activity relationship (QSAR)/ quantitative structure-property relationship (QSPR) models, this study explores the application of fullerene derivatives as nanocarriers for breast cancer chemotherapy drugs. Isolated drugs and two drug-fullerene complexes (i.e., drug-pristine C60 fullerene and drug-carboxyfullerene C60-COOH) were investigated with the protein CXCR7 as the molecular docking target. The research involved over 30 drugs and employed Pearson's hard-soft acid-base theory and common QSAR/QSPR descriptors to build predictive models for the docking scores. Energetic descriptors were computed using quantum chemistry at the density functional-based tight binding DFTB3 level. The results indicate that drug-fullerene complexes interact more with CXCR7 than isolated drugs. Specific binding sites were identified, with varying locations for each drug complex. Predictive models, developed using multiple linear regression and IBM Watson artificial intelligence (AI), achieved mean absolute percentage errors below 12%, driven by AI-identified key variables. The predictive models included mainly quantitative descriptors collected from datasets as well as computed ones. In addition, a water-soluble fullerene was used to compare results obtained by DFTB3 with a conventional density functional theory approach. These findings promise to enhance breast cancer chemotherapy by leveraging fullerene-based drug nanocarriers.

Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2-positive ABC patients with stable or active brain metastases (BMs); however, its efficacy in patients with HER2-low ABC with BMs is not well established yet. METHODS: DEBBRAH is a single-arm, five-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n = 6, asymptomatic untreated BMs) and 4 (n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. RESULTS: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. CONCLUSIONS: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.

High Levels of Superoxide Dismutase 2 Are Associated With Worse Prognosis in Patients With Breast Cancer.

OBJECTIVE: Breast cancer is classified based on hormone receptor status and human epidermal growth factor receptor 2 (HER2) expression, including luminal, HER2+, or triple-negative (TNBC). The absence of a therapeutic target in TNBC and the resistance to treatment associated with other subtypes means that research for new biomarkers remains important. In this context, superoxide dismutase 2 (SOD2) has emerged as a potential therapeutic target due to its clinicopathological associations and its ability to predict responses in human tumors. To analyze SOD2 staining in samples obtained from individuals with breast cancer and explore its transcriptional pattern across tumor subtypes. MATERIALS AND METHODS: SOD2 staining was assessed using the immunohistochemistry (IHC) in 80 samples from breast cancer patients. To analyze the expression profile at the transcriptional level, international databases such as cBioPortal (1,980 patients) and PrognoScan were accessed. RESULTS: Significant differences were observed between SOD2 expression analyzed by IHC, and estrogen (p = 0.0008) and progesterone (p = 0.0003) receptors, as well as tumor subtypes (p<0.0001). These differences were found in conjunction with other associations, including clinical and pathological data, such as tumor stage (p = 0.0129), tumor size (p = 0.0296), and node metastasis (p = 0.0486). Moreover, elevated SOD2 expression correlated with an unfavorable prognosis. The in silico analysis revealed a similar pattern, despite operating at the transcriptional level. Moreover, notable correlations were identified between elevated SOD2 expression and worse survival. CONCLUSION: These results highlight the importance of SOD2 in breast cancer, particularly in aggressive subtypes. Increased SOD2 staining correlates with poorer outcomes, suggesting it as a potential therapeutic target.