Early Diagnosis Of Breast Cancer Research Articles

An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

Emergence of Quantum Dots as Innovative Tools for Early Diagnosis and Advanced Treatment of Breast Cancer.

Quantum dots (QDs) semiconducting nanomaterials, have garnered attention due to their distinctive properties, including small size, high luminescence, and biocompatibility. In the context of triple-negative breast cancer (TNBC), notorious for its resistance to conventional treatments, QDs exhibit promising potential for enhancing diagnostic imaging and providing targeted therapies. This review underscores recent advancements in the utilization of QDs in imaging techniques, such as fluorescence tomography and magnetic resonance imaging, aiming at the early and precise detection of tumors. Emphasis is placed on the significance of QD design, synthesis and functionalization processes as well as their use in innovative strategies for targeted drug delivery, capitalizing on their ability to selectively deliver therapeutic agents to cancer cells. As the research in this field advances rapidly, this review covers a classification of QDs according to their composition, the characterization techniques than can be used to determine their properties and, subsequently, emphasizes recent findings in the field of TNBC-targeting, highlighting the imperative need to address challenges, like potential toxicity or methodologies standardization. Collectively, the findings explored thus far suggest that QDs could pave the way for early diagnosis and effective therapy of TNBC, representing a significant stride toward precise and personalized strategies in treating TNBC.

Improved PAA algorithm for breast mass detection in mammograms

Mammography screening is instrumental in the early detection and diagnosis of breast cancer by identifying masses in mammograms. With the rapid development of deep learning, numerous deep learning-based object detection algorithms have been explored for mass detection studies. However, these methods often yield a high false positive rate per image (FPPI) while achieving a high true positive rate (TPR). To maintain a higher TPR while also ensuring lower FPPI, we improved the Probability Anchor Assignment (PAA) algorithm to enhance the detection capability for mammographic characteristics with our previous work. We considered three dimensions: the backbone network, feature fusion module, and dense detection heads. The final experiment showed the effectiveness of the proposed method, and the TPR/FPPI values of the final improved PAA algorithm were 0.96/0.56 on the INbreast datasets. Compared to other methods, our method stands distinguished with its effectiveness in addressing the imbalance between positive and negative classes in cases of single lesion detection.

Abstract PO4-02-07: Prevalence of distant metastases in High-Risk Operable Breast Cancer (HROBC) pT1-2 N2a orhigher at diagnosis

Abstract Introduction: Current standard guidelines do not recommend a routine staging workup in early breast cancer as incidence of de novo metastasis is only 1-2%. Some of these patients are found to have a higher axillary nodal burden after surgery. This prospective study evaluated the incidence of distant metastases in clinically high-risk operable breast cancer (HROBC) who have a higher nodal burden on histopathological report after surgery. The intent was to detect presence of subclinical distant disease that may have an impact on treatment offered and outcome. Currently, there is no compelling data to support a routine metastatic workup in these patients. Methodology: A single-centre study approved by Institutional Ethics Committee was carried out enrolling early breast cancer patients with high nodal burden (four or more axillary nodes positive) after definitive surgery. The HROBC group was defined as early breast cancer patients with pT1/2, N2a/N3 stage on surgical histopathology. They underwent a comprehensive metastatic workup, including ultrasound abdomen, bone scan, and CT scan (thorax-abdomen-pelvis) or PET scan before starting their adjuvant treatment. Burden of distant disease was classified into oligometastatic (M1o) or polymetastatic disease (M1p). The adjuvant treatment intent was redefined as curative or palliative based on the distant disease burden and treatment was modified accordingly. Result: The study accrued 100 HROBC women with pT1-2, pN2a-3 stage disease during 2015-2018 operated upfront for early breast cancer cT1-2 N0-1, of which 97 were included in final analysis. The 3 excluded patients had their surgery elsewhere with clinical diagnosis of early breast cancer with histopathology indicating heavy nodal burden; 2 of them had T3 tumor and 1 had cN3 disease and were deemed a higher stage and would anyway warrant a metastatic work-up and hence were ineligible for the study. Forty percent women were premenopausal, 54 (55.6%) had pN2a disease and 43 (44.4%) had pN3. Staging investigations identified distant metastatic disease (M1) in 8 of 97 women (8.24%). Interestingly, 5 of them had oligometastatic (M1o) disease (5.15%) and 3 had polymetastatic (M1p) disease (3.09%). Between the 2 nodal groups, no specific distribution of M1o or M1p disease was observed, but the pickup rate of overall distant disease was higher in pN3 (11.4%) as against N2a (5.6%) patients p=NS. The most common sites of metastases observed was bone (5/8) followed by liver (3/8). There was no correlation with ER, PgR or HER2neu status and extent of distant disease. The patients with M1o disease, completed their adjuvant treatment as planned along with treatment of oligometastatic sites. Only 3.09% patients who were detected with M1p disease, were treated with a palliative systemic therapy. Conclusion: Early detection of metastatic disease, M1o and M1p, in clinical HROBC could lead to improved treatment strategies. The findings have the possibility to optimize management of high-risk early breast cancer as a separate clinical entity, requiring staging post hoc after primary surgery, for adequate resource stratification and better outcomes, especially in those with 10 or more axillary nodes positive for metastases. This subset may get identified in the TNM classification for better understanding and management. Citation Format: Vani Parmar, Naveena Kumar AN, Basila Ameer Ali, Nita Nair, Shalaka Joshi, Purvi Thakkar, Garvit Chitkara, Varsha Gaikwad, Vaibhav Vanmali, Shabina Siddique, Palak Popat, Sneha Shah, Sangeeta Desai, Tanuja Shet, Meenakshi Thakur, Venkatesh Rangarajan, Rajendra Badwe. Prevalence of distant metastases in High-Risk Operable Breast Cancer (HROBC) pT1-2 N2a orhigher at diagnosis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-07.

Abstract PO5-02-03: Does the recommendation of adjuvant CDK4/6 inhibitors implicate more ovarian suppression in premenopausal patients? A real-world study of a public and a private Argentinean institution

Abstract Introduction The recently published NATALEE trial has reported an increase of invasive disease free survival with the addition of ribociclib to hormone therapy during 3 years. Given the fact that aromatase inhibitors are required as the endocrine therapy backbone, premenopausal patients require ovarian function suppression (OFS) during CDKi treatment In the era of CDKi in the adjuvant setting, we hypothesize that the recommendation of GnRh analogs administration in addition to aromatase inhibitors will increase for premenopausal patients, given the inclusion criteria of this pivotal trial. For this reason, we explored in a retrospective cohort of a public and a private Argentinean institution to define whether the application of these criteria would imply an increase of the recommendation of OFS as part of the adjuvant endocrine treatment. Methods This was a multicentric retrospective cohort comprising premenopausal patients with early breast cancer diagnosis. Descriptive statistics were used to summarize data. The criteria for defining ribociclib recommendations were based on the phase III NATALEE clinical trial. Univariate analysis, including t and chi-square tests were used to determine differences between the populations that received and did not receive OFS, and between both participating institutions. p&amp;lt; 0,05 was considered to evaluate statistical significance. Results 191 premenopausal patients were incorporated in our analysis, and 48 (25.1%) received OFS. In this subgroup, mean age was lower (38.1 vs 44.2 years; p&amp;lt; 0.001) and the incidence of T3 (23.9 vs 6.5%; p=0.002), node-positive tumors (57.4 vs 28.9%; p=0.005), and prior chemotherapy treatment (75.5 vs 58.8%; p&amp;lt; 0.001) was higher. Among the 143 patients that did not receive OFS, 121 (84.6%) would have fulfilled clinical trial criteria for receiving ribociclib. No differences were observed according to the treating institution: 80.3 vs 87.8%; (p=0.22). The patient subgroup that would have met NATALEE criteria and did not receive OFS, had median age of 44.19 (SD 4.18), and had prior chemotherapy in 63.8% of the cases. Considering these characteristics, we observed that chemotherapy-induced amenorrhea and local institutional guidelines were the main explanations to understand why these moderate and high-risk patients did not receive OFS. Conclusion We observed that in premenopausal patients, the application of NATALEE criteria would result in an increase of the recommendation of GnRh analogues in around 80% of patients that had not received OFS in a retrospective cohort. This scenario may result in new challenges in treatment adherence and quality of life. In addition, this information is of special importance to carefully analyze the financial toxicity of a modern adjuvant approach that will be applied in a high proportion of eBC patients, especially in low and middle-income countries. Citation Format: Vanesa Lopez, Dana Narvaez, Jorge Nadal, Federico Waisberg, Adrian Nervo, Victoria Costanzo, Claudio Paletta, Fernando E. Petracci, Sergio Rivero, Alexis Ostinelli, Matías Chacón, Andrea Aguilar, Alejandro Kuzminin, Ageles Nico, Evelina Rovera, Naima Kassis, Maria Zapata Camaño, Carolina Almada, Maria Savignano, Gustavo Roganovich, Maria Eugenia Azar, Valeria Caceres. Does the recommendation of adjuvant CDK4/6 inhibitors implicate more ovarian suppression in premenopausal patients? A real-world study of a public and a private Argentinean institution [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-03.

Abstract PO2-09-12: The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort

Abstract Objective Previous studies showed that various outcomes in patients with early breast cancer (EBC), from incidence to survival, were influenced by social factors. However, there is limited research on the socioeconomic inequalities in quality of life (QoL) after treatment for EBC, and the magnitude and changes over time of these inequalities have not been quantified. This study examines the socioeconomic inequalities in QoL and their time trends among a large cohort of patients with EBC. Methods We conducted a comprehensive longitudinal analysis using data from the prospective multicentric CANTO study (CANcer TOxicity, NCT01993498), which included participants with EBC enrolled between 2012 and 2018. QoL was assessed using the summary score of the EORTC QLQ-C30 questionnaire at the time of diagnosis and 1 and 2 years post-diagnosis. We included patients with complete QoL data at diagnosis and 2 years post-diagnosis. Analyses were conducted for three indicators of socioeconomic status separately: self-reported financial difficulties, household income and educational level. We first analyzed trajectories of QoL by socioeconomic status from diagnosis to Year 1 and Year 2. Then, social inequalities in QoL were estimated using the regression-based slope indexes of inequality (SII) and compared across the follow-up periods. The SII represents the absolute change in the QLQ-C30 summary score along the two extremes of the socioeconomic gradient, taking into account the intermediate groups and their relative sizes. The analyses were adjusted for age at diagnosis, Charlson comorbidity index, disease stage, use and type of endocrine therapy, use and type of chemotherapy, breast surgery, radiotherapy use, and lymph node management. Results In the 5915 analyzed patients, compared to those with higher socioeconomic status, those reporting a high level of financial difficulty, lower income, or lower education were younger, most often premenopausal, with comorbidities, diagnosed with stage III BC, and treated with mastectomy and axillary lymph node dissection. There were no differences between socioeconomically-defined groups concerning BC histology, grade and IHC-defined subtype. Social inequalities in QoL at baseline were statistically significant for all socioeconomic status indicators (SIIfinancial difficulties = -7.6 [-8.9;-6.2], SIIincome= -4.0 [-5.2;-2.8]) and SIIeducation= -1.9 [-3.1;-0.7]). In multivariable analyses, social inequalities significantly increased (interaction p&amp;lt; 0.05) in Year 1 (SIIfinancial difficulties = -11.1 [-12.8;-9.4], SIIincome= -6.5 [-8.0;-5.0] and SIIeducation= -5.0 [-6.6;-3.5]) and Year 2 (SIIfinancial difficulties = -10.7 [-12.2;-9.1], SIIincome= -6.7 [-8.0;-5.3] and SIIeducation= -4.7 [-6.1;-3.3]) suggesting a widening socioeconomic gap in QoL outcomes irrespective of pre-diagnosis health, tumor characteristics and treatment. Similar results were observed in subgroups defined by menopausal status (pre/postmenopausal) and type of systemic treatment (chemotherapy, endocrine therapy). Conclusion Our study highlights and quantifies the association of several individual socioeconomic indicators with the QoL of patients with EBC in France. The magnitude of socioeconomic inequalities in QoL increased over time after EBC diagnosis in a country with a strong welfare system and universal healthcare coverage. In the era of precision medicine, these results underscore the importance of developing interventions to improve precision care, considering the conditions in which people are born, grow, work, live and age and the wider set of forces and systems shaping the conditions of daily life. Citation Format: José Luis Sandoval, Antonio Di Meglio, Arlindo Ferreira, Maria Alice Franzoi, Fabrice André, Barbara Pistilli, Christelle Jouannaud, Marion Fournier, Philippe Rouanet, Asma Dhaini Mermeche, Paul Cottu, Sibille Everhard, Anne-Laure Martin, Silvia Stringhini, Idris Guessous, Ines Vaz Luis, Gwenn Menvielle. The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-12.

Abstract PO1-07-03: An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography

Abstract Objectives: Our study aims to develop an accurate and comprehensive deep neural network capable of classifying CESM images to aid in the early detection and diagnosis of breast cancer in clinical settings. Methods: We enrolled diagnostic CESM examinations conducted between January 1, 2019 and January 17, 2021. We developed and tested the performance of a multi-feature fusion network for breast lesion classification by combining low-energy (LE) and dual-energy subtracted (DES) images, dual-view, and bilateral information using a large and diverse CESM dataset. We have evaluated the ability of the proposed network to generalize on external datasets and the results were reported using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: In the study period 1973CESMs were included. Mean age was 53 years ± 12 (standard deviation). In the internal test dataset, the model with CESM (LE +DES) inputs combined not only bilateral information (left and right breasts) but also dualview information (CC and MLO), achieved best diagnosis performance with AUC of 0.96 [95% confidence interval (CI): 0.95–0.97], accuracy of 0.9 [95% confidence interval (CI): 0.88–0.92], sensitivity of 0.84 [95% confidence interval (CI): 0.80–0.88] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95], while the model with LE inputs only got an AUC of 0.94 [95% (CI): 0.93–0.95], accuracy of 0.88 [95% confidence interval (CI): 0.86–0.90], sensitivity of 0.79 [95% confidence interval (CI): 0.74–0.83] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95] (external dataset: an AUC of 0.90 [95% (CI): 0.85–0.94], accuracy of 0.84 [95% confidence interval (CI): 0.78–0.89], sensitivity of 0.77 [95% confidence interval (CI): 0.61–0.88] and specificity of 0.87 [95% confidence interval (CI):0.80–0.92]). Conclusion: CESM is a promising technique in breast cancer diagnosis due to its high feasibility and potential. The results demonstrate that left-right breast fusion and dual-view fusion are helpful for accurate diagnosis on CESM images. Specifically, dual-energy subtracted (DES) images generated by CESM improve diagnostic accuracy when compared to low-energy (LE) images alone. Keywords: Contrast-enhanced spectral mammography; Deep neural network; Breast cancer diagnosis; Multi-feature fusion Citation Format: Yipeng Song, Wei Jiang. An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-03.

Abstract PO4-26-02: Evaluation of Tumor Infiltrating Lymphocytes as a predictive biomarker of recurrence in patients with Ductal Carcinoma In Situ of the breast

Abstract Introduction: Ductal carcinoma in situ (DCIS) represents around 20% of early breast cancer diagnoses globally. Some studies evaluated risk factors associated with DCIS recurrence. Among these, age, surgical margins, comedonecrosis (CN), high nuclear grade, negative hormone receptors and HER2 expression stand out. Recent approaches have been evaluating the role of the immune microenvironment and its association with recurrence and progression of DCIS. Objective: To evaluate the association between Tumor Infiltrating Lymphocytes (TILs) in DCIS samples and disease recurrence. To characterize the immunological microenvironment of DCIS, analyzing the presence of TILs, “touching TILs” and desmoplastic reaction and their association with recurrence. Epidemiological, clinical, histological and immunohistochemical (IHC) characteristics were also evaluated. Methods: This is a retrospective cohort study with patients diagnosed with DCIS and treated at Sao Paulo State Cancer Institute and Hospital das Clinicas of University of Sao Paulo. We included women over 18 years old with a diagnosis of DCIS who underwent treatment from Jan/2007 to Dec/2020. Male patients, patients with a diagnosis of invasive or microinvasive disease in the anatomopathological examination of the surgical specimen or patients with history of any neoplasm were excluded. The main outcome was survival analysis according to the quantification of TILs, adjusted for potential confounders. For that, we collected data on age, presence of palpable mass, imaging findings, histological and IHC characteristics, such as expression of estrogen receptor (ER), progesterone receptor (PR) and hyperexpression of HER2, type of surgical approach, type of radiation therapy, use of endocrine therapy, length of follow-up, recurrence, and its type. Two pathologists evaluated TILS in the sample with the highest tumor representation and numerically quantified it as percentage. They also evaluated the presence of “touching tils” (lymphocytes in contact with the basement membrane) and desmoplastic reaction in the tumor stroma. Kaplan-Meier curves, log-rank tests and Cox regression models were used to evaluate survival. Chi-square tests were used to evaluate the association between categorical variables. Results: 283 patients met the eligibility criteria. Mean age of patients was 55 years. 15% had a palpable nodule at physical examination. Clustered amorphous microcalcifications were the most prevalent mammographic presentation, found in 41% of the patients. The most frequent histological and IHC features were cribriform presentation (73%) and ER positivity (86%), respectively. Desmoplastic reaction was absent in 10.5%, discreet in 51.9%, moderate in 24% and intense in 13.6% of the patients. Breast conserving surgery was performed in 189 patients, and 100 of them received adjuvant radiation therapy. Mean follow-up was 77.2 months, with a recurrence rate of 9.2%. We observed that tumors with focal necrosis (HR 6.4 [1.39-34.71] p 0.018) or CN (HR 4.53 [1.34 – 15.28] p 0.015) had higher risks of recurrence. Patients with a percentage value of TILs greater than or equal to 17% also had a higher risks of recurrence (HR 2.97 (1.17-7.51) p 0.02). These patients were mostly under 65 years of age (OR 0.45 [0.21 - 0.97] p 0.049). In a multivariate model, CN and TILs&amp;gt;17% remained significantly associated with recurrence (p=0.034 and p=0.035 respectively). There was a trend for invasive recurrence in 76.9% of the patients that relapsed when TILS were greater than or equal to 17% (p 0.062). “Touching TILs” were present in 12.9% of the patients but were not associated with recurrence (p=0.575). Conclusion: In our cohort, high value of TILs (&amp;gt;= 17%) and presence of CN were independently associated with DCIS recurrence. Our findings suggest that TILS are a prognostic immunological biomarker in DCIS and warrant further investigation in prospective trials to determine the most adequate cut-point. Citation Format: Camila Pasetto, Fernando Aguiar, Marcella Peixoto, Maira Doria, Bruna Mota, Jonathan Maesaka, Jose Roberto Filassi, Edmund Baracat, Rodrigo Gonçalves. Evaluation of Tumor Infiltrating Lymphocytes as a predictive biomarker of recurrence in patients with Ductal Carcinoma In Situ of the breast [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-02.

Diagnostic Potential Role of CXCL3 and Leptin Levels in Breast Cancer

The risk of breast cancer development is believed to be attributed to the alterations of a number of key biological components. Within this context, elevated levels of some chemokines that act as growth factors and can promote cancer development. The current study was designed to evaluate CXCL3 (a chemokine C-X-C Motif Ligand 3) and leptin (a peptide hormone synthesized by adipose tissue with cytokine activity) serum of Iraqi breast cancer patients in comparison to healthy controls. A total of 90 participants consisted of 60 patients diagnosed with breast cancer and 30 healthy women as control group were enrolled into this case-control study. Venous blood samples were collected from all participants to evaluate CXCL3 and leptin serum levels using ELISA. The results demonstrated significantly (P≤0.001) higher mean levels of CXCL3 and leptin in breast cancer patients (1.19±0.10 ng/mL and 130.44± 3.72pg/mL) compared to those of their healthy counterparts (0.430± 0.02\ng/mL and 57.1± 3.2pg/mL respectively). Interestingly, vast majority of the assessed breast cancer cases (up to 95-98%) showed to have elevated serum levels of both of the assessed potential biomarkers (CXCL3 and leptin). The present study results suggest an association of both CXCL3 and leptin in breast cancer pathogenicity. This supports the possibility of utilizing these potential biomarkers for breast cancer early detection and diagnosis.

Small animal PET imaging with the 68Ga-labeled pH (low) insertion peptide-like peptide YJL-4 in a triple-negative breast cancer mouse model

BackgroundThe aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator 1,4,7‑triazacyclononane-N,N′,N″-triacetic acid (NOTA), the peptide was labeled with 68Ga. Then, the biodistribution of 68Ga-YJL-4 in tumor-bearing nude mice was investigated, and the mice were imaged by small animal positron emission tomography (PET).ResultsThe radiochemical yield and radiochemical purity of 68Ga-YJL-4 were 89.5 ± 0.16% and 97.95 ± 0.06%, respectively. The biodistribution of 68Ga-YJL-4 in tumors (5.94 ± 1.27% ID/g, 6.72 ± 1.69% ID/g and 4.54 ± 0.58% ID/g at 1, 2 and 4 h after injection, respectively) was significantly greater than that of the control peptide in tumors at the corresponding time points (P < 0.01). Of the measured off-target organs, 68Ga-YJL-4 was highly distributed in the liver and blood. The small animal PET imaging results were consistent with the biodistribution results. The tumors were visualized by PET at 2 and 4 h after the injection of 68Ga-YJL-4. No tumors were observed in the control group.ConclusionsThe novel pHLIP family peptide YJL-4 can adopt an α-helical structure for easy insertion into the cell membrane in an acidic environment. 68Ga-YJL-4 was produced in high radiochemical yield with good stability and can target TNBC tissue. Moreover, the strong concentration of radioactive 68Ga-YJL-4 in the abdomen does not hinder the imaging of early TNBC.

FS-WOA-stacking: A novel ensemble model for early diagnosis of breast cancer

In this paper, a new integrated scheme is proposed to accurately predict breast cancer, help doctors make early diagnosis and treatment plans, and improve the prognosis of patients. We selects five mainstream machine learning models: support vector machine (SVM), artificial neural network (ANN), random forest (RF), extreme gradient boosting (XGBoost) and adaptive boosting (AdaBoost). The Wisconsin Breast Cancer Database (WBCD) and Wisconsin Diagnostic Breast Cancer (WDBC) are used as datasets to investigate the predictive performance of these single and ensemble models. Then, we use multiple linear regression method for feature selection (FS), the experimental results show that the change of feature subset will significantly affect the performance of the model. The recall and f1-score of the five models are improved by 1.19% and 0.84% on average. After that, we apply whale optimization algorithm (WOA) to optimize the hyperparameters of the model to improve their prediction performance. In the best-case scenario, the model demonstrated improvements of 1.02% in accuracy and 1.82% in precision. In addition, we ensemble these models by stacking, investigate the performance changes of the ensemble model when different models are used as meta learners. Finally, the FS-WOA-Stacking model achieves 99.56% accuracy on WBCD and 99.65% accuracy on WDBC. Compared with the existing breast cancer prediction models, the performance of the proposed model is at an excellent level.

Fe3O4-Cy5.5-trastuzumab magnetic nanoparticles for magnetic resonance/near-infrared imaging targeting HER2 in breast cancer

This study developed a probe Fe3O4-Cy5.5-trastuzumab with fluorescence and magnetic resonance imaging functions that can target breast cancer with high HER2 expression, aiming to provide a new theoretical method for the diagnosis of early breast cancer. Fe3O4-Cy5.5-trastuzumab nanoparticles were combined with Fe3O4 for T2 imaging and Cy5.5 for near-infrared imaging, and coupled with trastuzumab for HER2 targeting. We characterized the nanoparticles used transmission electron microscopy, hydration particle size, Zeta potential, UV and Fourier transform infrared spectroscopy, and examined its magnetism, fluorescence, and relaxation rate related properties. CCK-8 and blood biochemistry analysis evaluated the biosafety and stability of the nanoparticles, and validated the targeting ability of Fe3O4-Cy5.5 trastuzumab nanoparticles through in vitro and in vivo cell and animal experiments. Characterization results showed the successful synthesis of Fe3O4-Cy5.5-trastuzumab nanoparticles with a diameter of 93.72 ± 6.34 nm. The nanoparticles showed a T2 relaxation rate 42.29 mM−1s−1, magnetic saturation strength of 27.58 emg g−1. Laser confocal and flow cytometry uptake assay showed that the nanoparticles could effectively target HER2 expressed by breast cancer cells. As indicated by in vitro and in vivo studies, Fe3O4-Cy5.5-trastuzumab were specifically taken up and effectively aggregated to tumour regions with prominent NIRF/MR imaging properties. CCK-8, blood biochemical analysis and histological results suggested Fe3O4-Cy5.5-trastuzumab that exhibited low toxicity to major organs and good in vivo biocompatibility. The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2 imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer.

Quantification of MicroRNA in a Single Living Cell via Ionic Current Rectification-Based Nanopore for Triple Negative Breast Cancer Diagnosis.

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.

A ratiometric electrochemical biosensor based on ARGET ATRP for detection of HER2 gene

Human epidermal growth factor receptor 2 (HER2), a common proto-oncogene, is overexpressed in a subset of breast cancer patients. It is essential to track HER2 expression for early breast cancer diagnosis. Herein, a ratiometric electrochemical biosensor for detection of HER2 based on activators generated by electron transfer for atom transfer radical polymerisation (AGET ATRP) and hairpin DNA was developed. Specifically, hairpin DNA was first self-assembled on the gold electrode by Au–S bond. Upon capturing HER2, the stem-loop structure of hairpin DNA was unfolded, the signal value of methylene blue (MB) decreased as it moved away from the electrode surface. cDNA was linked with HER2 by complementary base pairing to introduce amino group. Then, the initiator 2-bromo-2-methylpropionic acid (BMP) were connected to the amino group on the cDNA to activate ARGET ATRP. The detection performance of biosensors for HER2 was explored by the ratio signal between two signal molecules. Under optimal conditions, this ratiometric electrochemical biosensor shows good selectivity and stability with a wide detection range of 1–1 × 106 pM and a detection limit of 78.47 fM. Furthermore, the biosensor exhibits satisfactory anti-interference ability due to the hairpin DNA and dual signal system, and has promising application prospects in the detection of other DNA disease markers.

Experiences of family caregivers in dealing with cases of advanced breast cancer: a qualitative study of the sociocultural context in Punjab, Pakistan

BackgroundPatients with advanced breast cancer require consistent help and support from family caregivers. These caregivers often endure financial burdens and psychological stress, with their experiences significantly influenced by sociocultural factors. This study aims to explore the experiences of family caregivers of advanced breast cancer patients in Punjab province, Pakistan.MethodsData was collected through in-depth interviews with fifteen family caregivers of advanced breast cancer patients in three major cities of Punjab, Pakistan. Caregivers, who had been in close contact with the patient for the last two years, were purposively sampled from five major hospitals. The data was analyzed using thematic analysis.ResultsThe study revealed that the experiences of family caregivers are deeply rooted in the sociocultural context. Key themes identified include social responsibility and cultural reciprocity norms; limited awareness and mobility options for caregivers; financial responsibility and strain; impacts of beauty myths and shyness on caregiving attitudes and decisions; the stressful and emotional nature of caregiving; treatment perspectives influenced by social groups; challenges in consulting male physicians and associated stigma; the role of religious beliefs in caregiving; and stress management, with religion often being a coping mechanism. These factors can contribute to delayed treatment decisions for patients.ConclusionsFamily caregivers are crucial in facilitating timely treatment decisions for advanced breast cancer patients in the Pakistani context. To minimize treatment delays and alleviate caregiver stress, addressing sociocultural barriers in care-seeking is essential. A tailored approach, considering sociocultural and religious factors, is imperative for the management and early diagnosis of breast cancer, necessitating appropriate policymaking and implementation.

Exploring research progress in studying serum exosomal miRNA-21 as a molecular diagnostic marker for breast cancer.

Breast cancer is one of the most prevalent malignancies affecting women globally and poses a significant public health challenge. Early clinical detection plays a pivotal role in providing optimal treatment opportunities and favorable prognoses, crucial for reducing breast cancer mortality and enhancing patients' quality of life. Therefore, the timely identification and diagnosis of breast cancer are imperative. Conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3), serve as reliable methods for actively monitoring disease progression and have become a routine auxiliary diagnostic approach in clinical settings. However, these biomarkers exhibit limitations in sensitivity and specificity, particularly in the early screening and diagnosis of tumors, often yielding results inconsistent with clinical manifestations. In recent years, research has increasingly focused on exosomes released by tumor cells as potential new biomarkers for early stage breast cancer screening. Exosomes carry various components, including tumor-derived proteins, nucleic acids, and lipids. This paper delves into the specific utilization of serum exosomal microRNA-21 (miR-21) as a biomarker for early detection and diagnosis of breast cancer, evaluating its efficacy within this framework.

A novel photoelectrochemical biosensing platform utilizing dual Type-II Bi2O3/CdLa2S4/Bi2S3 ternary heterojunctions as signal transduction materials and Cu2O nanosphere as a sensitizer for CA15-3 detection

Sensitive detection of CA15-3 is important for postoperative monitoring and early diagnosis of breast cancer. In this work, a photoelectrochemical (PEC) biosensing platform was constructed of CA15-3 by using Bi2O3/CdLa2S4/Bi2S3 ternary type-II heterojunction as the photoactive transduction material for sensitive detection, and the raspberry-shaped Cu2O nanospheres were exploited as the signal sensitizing tags. On one hand, the use of Bi2S3 as a sensitizer can effectively enhance the visible light excitation of the substrate material. On the other hand, Bi2S3 and Bi2O3/CdLa2S4 have the ability to create dual type-II heterojunctions with matched energy levels, which significantly enhances the separation and migration efficiency of the photogenerated carriers and effectively suppresses the recombination of the e-/h+ pairs. Raspberry-like semiconducting Cu2O nanospheres can mediate the PEC process of the heterojunctions. An immunosensor was developed combining the signal transduction capacity of ternary heterojunction and the signal sensitizing effect of Cu2O nanospheres. The proposed PEC immunosensor showed good selectivity and stability for detecting CA15-3 (0.001 ∼ 100 U/mL) with a detection limit of 0.0003 U/mL (S/N = 3). The constructed PEC immunosensor had potential applications in the clinical detection of CA15-3, and was expected to play a great role in the early diagnosis of breast cancer in the future. Moreover, in the design engineering of photoactive materials, the improvement of visible excitation and the enhancement of carrier separation efficiency have been realized simultaneously using a single material, which provides new ideas for the design of photoactive materials.

The application of mammography imaging in the diagnosis and prediction of breast diseases

Breast diseases pose a significant threat to women’s health, so early detection and treatment are extremely important. In this context, early disease identification has become crucial in the diagnosis and treatment of breast diseases. This paper begins by outlining the pivotal role of mammography in the early diagnosis of breast cancer, comparing the structural similarities and differences between normal and diseased breast tissues. This comparison underscores the primary role of mammography in the diagnosis and treatment of breast diseases. Additionally, our paper provides an overview of fundamental concepts related to breast cancer detection, diagnosis, and prediction systems. It delves into the latest research developments in auxiliary diagnostic detection, examination, and risk prediction systems associated with breast cancer. Our objective is to offer a comprehensive understanding of the role of computer-aided detection, diagnosis, and prediction systems in breast diseases, fostering further development and application. This work aims to explore and drive innovation in the field, enhance early detection rates of breast diseases, and guide readers towards novel directions, thus contributing to female healthcare management.

Association between sociodemographic factors and health beliefs related to breast cancer screening behavior among Northern Thai women: a hospital-based study

Early diagnosis of breast cancer is crucial for reducing mortality rates. The purpose of this study is to determine the impact of demographics/social determinants of health on beliefs about the practice of self-breast examination, using mammogram and ultrasound in the context of breast cancer screening among Thai women in a hospital-based setting for implying program planning and future research. A cross-sectional study was conducted in two health centers in Chiang Mai Province from August 2021 to December 2021, involving 130 Thai women ages 40 to 70 years. Data were collected by a survey using a questionnaire to gather sociodemographic information, and health beliefs about breast cancer and screening behavior utilizing the modified Thai version of Champion's Health Belief Model Scale (MT-CHBMS). Descriptive statistics, t-tests, ANOVA, and linear regression models were employed for examining association between sociodemographic factors and health beliefs about the practice of self-breast examination (BSE), using mammogram (MG) and ultrasound (UTS). Health insurance schemes were associated with Benefit-MG, Barrier-BSE, Barrier-MG and Barrier-UTS subscales. Additionally, monthly income was associated with Barrier-MG and Barrier-UTS subscales. The most common barriers reported were “embarrassment”, “worry”, and “takes too much time”. To enhance breast cancer screening in Thailand, program planning and future research should focus on health insurance schemes, especially women with social security schemes, as they may be the most appropriate target group for intervention.

Breast Cancer Diagnosis Among Mexican Participants: A Qualitative Study

Objective: We aimed to describe the timely perceived diagnosis of Breast Cancer (BC) among fifteen participants living in western Mexico, as well as both the time points and intervals for diagnosing BC. Design: A qualitative study with a phenomenological approach was conducted. Site: Instituto Jalisciense de Cancerología (Cancer Institute of Jalisco, IJC per the Spanish acronym), a tertiary care hospital for cancer patients run by the Ministry of Health of the State of Jalisco, Mexico, located in the city of Guadalajara, which is the capital of the state. Participants: fifteen female participants living in the state of Jalisco and whose histopathological diagnosis of BC was made at IJC during the 2013-2017 period. Methods: semi-structured interviews were conducted. The ATLAS.ti program was used for content analysis. Results: twelve participants received a late diagnosis (stages IIB-IV). However, they considered that their diagnoses were timely. Most of the participants stated they perceived a positive timely diagnosis, because they considered that being alive is attributable to a timely diagnosis, which is related to seeking medical care quickly and the work and procedures made by the health professionals. Conclusions: the perception of the female participants regarding the diagnosis timeliness can be quite different from that of the clinical stage made by the doctors. A combination of beliefs, culture, inequities in access and quality of health services, as well as the fear of having BC contributed to increase the time spent when seeking and receiving medical care. Thus, health education for early BC diagnosis is strongly recommended.