Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer.

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.60%) expression in multidrug-resistant BC cells, facilitates immune evasion by low-immunogenic senescent escape CSCs. CALD1, upregulated in ADR-resistant BC, promoting senescent-escape of CSCs with an anti-apoptosis state and upregulating CD276, PD-L1 to promote chemoresistance and immune escape. We have developed a controlled-released thermosensitive hydrogel containing pH- responsive anti-CD276 scFV engineered biomimetic nanovesicles to overcome BC in primary, recurrent, metastatic and abscopal humanized mice models. Nanovesicles coated anti-CD276 scFV selectively fuses with cell membrane of senescent-escape CSCs, then sequentially delivers siCALD1 and ADR due to pH-responsive MnP shell. siCALD1 together with ADR effectively induce apoptosis of CSCs, decrease expression of CD276 and PD-L1, and upregulate MHC I combined with Mn2+ to overcome chemoresistance and promote CD8+T cells infiltration. This combined therapeutic approach reveals insights into immune surveillance evasion by senescent-escape CSCs, offering a promising strategy to immunotherapy effectiveness in cancer therapy.

Electrochemical biosensors for early detection of breast cancer.

Breast cancer continues to be a significant contributor to global cancer deaths, particularly among women. This highlights the critical role of early detection and treatment in boosting survival rates. While conventional diagnostic methods like mammograms, biopsies, ultrasounds, and MRIs are valuable tools, limitations exist in terms of cost, invasiveness, and the requirement for specialized equipment and trained personnel. Recent shifts towards biosensor technologies offer a promising alternative for monitoring biological processes and providing accurate health diagnostics in a cost-effective, non-invasive manner. These biosensors are particularly advantageous for early detection of primary tumors, metastases, and recurrent diseases, contributing to more effective breast cancer management. The integration of biosensor technology into medical devices has led to the development of low-cost, adaptable, and efficient diagnostic tools. In this framework, electrochemical screening platforms have garnered significant attention due to their selectivity, affordability, and ease of result interpretation. The current review discusses various breast cancer biomarkers and the potential of electrochemical biosensors to revolutionize early cancer detection, making provision for new diagnostic platforms and personalized healthcare solutions.

In-silico study of the impact of system design parameters on microcalcification detection in wide-angle digital breast tomosynthesis.

Purpose: Accurate detection of microcalcifications ( µ Calcs ) is crucial for the early detection of breast cancer. Some clinical studies have indicated that digital breast tomosynthesis (DBT) systems with a wide angular range have inferior µ Calc detectability compared with those with a narrow angular range. This study aims to (1) provide guidance for optimizing wide-angle (WA) DBT for improving µ Calcs detectability and (2) prioritize key optimization factors. Approach: An in-silico DBT pipeline was constructed to evaluate µ Calc detectability of a WA DBT system under various imaging conditions: focal spot motion (FSM), angular dose distribution (ADS), detector pixel pitch, and detector electronic noise (EN). Images were simulated using a digital anthropomorphic breast phantom inserted with 120 µ m µ Calc clusters. Evaluation metrics included the signal-to-noise ratio (SNR) of the filtered channel observer and the area under the receiver operator curve (AUC) of multiple-reader multiple-case analysis. Results: Results showed that FSM degraded µ Calcs sharpness and decreased the SNR and AUC by 5.2% and 1.8%, respectively. Non-uniform ADS increased the SNR by 62.8% and the AUC by 10.2% for filtered backprojection reconstruction with a typical clinical filter setting. When EN decreased from 2000 to 200 electrons, the SNR and AUC increased by 21.6% and 5.0%, respectively. Decreasing the detector pixel pitch from 85 to 50 µ m improved the SNR and AUC by 55.6% and 7.5%, respectively. The combined improvement of a 50 µ m pixel pitch and EN200 was 89.2% in the SNR and 12.8% in the AUC. Conclusions: Based on the magnitude of impact, the priority for enhancing µ Calc detectability in WA DBT is as follows: (1) utilizing detectors with a small pixel pitch and low EN level, (2) allocating a higher dose to central projections, and (3) reducing FSM. The results from this study can potentially provide guidance for DBT system optimization in the future.

Estimation of the absorbed dose in simultaneous digital breast tomosynthesis and mechanical imaging.

Purpose: Use of mechanical imaging (MI) as complementary to digital mammography (DM), or in simultaneous digital breast tomosynthesis (DBT) and MI - DBTMI, has demonstrated the potential to increase the specificity of breast cancer screening and reduce unnecessary biopsies compared with DM. The aim of this study is to investigate the increase in the radiation dose due to the presence of an MI sensor during simultaneous image acquisition when automatic exposure control is used. Approach: A radiation dose study was conducted on clinically available breast imaging systems with and without an MI sensor present. Our estimations were based on three approaches. In the first approach, exposure values were compared in paired clinical DBT and DBTMI acquisitions in 97 women. In the second approach polymethyl methacrylate (PMMA) phantoms of various thicknesses were used, and the average glandular dose (AGD) values were compared. Finally, a rectangular PMMA phantom with a 45 mm thickness was used, and the AGD values were estimated based on air kerma measurements with an electronic dosemeter. Results: The relative increase in exposure estimated from digital imaging and communications in medicine headers when using an MI sensor in clinical DBTMI was 11.9 % ± 10.4 . For the phantom measurements of various thicknesses of PMMA, the relative increases in the AGD for DM and DBT measurements were, on average, 10.7 % ± 3.1 and 11.4 % ± 3.0 , respectively. The relative increase in the AGD using the electronic dosemeter was 11.2 % ± < 0.001 in DM and 12.2 % ± < 0.001 in DBT. The average difference in dose between the methods was 11.5 % ± 3.3 . Conclusions: Our measurements suggest that the use of simultaneous breast radiography and MI increases the AGD by an average of 11.5 % ± 3.3 . The increase in dose is within the acceptable values for mammography screening recommended by European guidelines.

Visible-short wavelength near infrared hyperspectral imaging coupled with multivariate curve resolution-alternating least squares for diagnosis of breast cancer.

This study investigates the application of visible-short wavelength near-infrared hyperspectral imaging (Vis-SWNIR HSI) in the wavelength range of 400-950 nm and advanced chemometric techniques for diagnosing breast cancer (BC). The research involved 56 ex-vivo samples encompassing both cancerous and non-cancerous breast tissue from females. First, HSI images were analyzed using multivariate curve resolution-alternating least squares (MCR-ALS) to exploit pure spatial and spectral profiles of active components. Then, the MCR-ALS resolved spatial profiles were arranged in a new data matrix for exploration and discrimination between benign and cancerous tissue samples using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The PLS-DA classification accuracy of 82.1 % showed the potential of HSI and chemometrics for non-invasive detection of BC. Additionally, the resolved spectral profiles by MCR-ALS can be used to track the changes in the breast tissue during cancer and treatment. It is concluded that the proposed strategy in this work can effectively differentiate between cancerous and non-cancerous breast tissue and pave the way for further studies and potential clinical implementation of this innovative approach, offering a promising avenue for improving early detection and treatment outcomes in BC patients.

MRPL13 is a metastatic and prognostic marker of breast cancer: A silico analysis accompanied with experimental validation.

BACKGROUND: Although progress has been made in accurate diagnosis and targeted treatments, breast cancer (BC) patients with metastasis still present a grim prognosis. With the continuous emergence and development of new personalized and precision medicine targeting specific tumor biomarkers, there is an urgent need to find new metastatic and prognostic biomarkers for BC patients. METHODS: We were dedicated to identifying genes linked to metastasis and prognosis in breast cancer through a combination of in silico analysis and experimental validation. RESULTS: A total of 25 overlap differentially expressed genes were identified. Ten hub genes (namely MRPL13, CTR9, TCEB1, RPLP0, TIMM8B, METTL1, GOLT1B, PLK2, PARL and MANBA) were identified and confirmed. MRPL13, TCEB1 and GOLT1B were shown to be associated with the worse overall survival (OS) and were optionally chosen for further verification by western blot. Only MRPL13 was found associated with cell invasion, and the expression of MRPL13 in metastatic BC was significantly higher than in primary BC. CONCLUSION: We proposed MRPL13 could be a potential novel biomarker for the metastasis and prognosis of breast cancer.

Preliminary investigation of MMP8 (rs11225395) and MMP9 (rs3787268) polymorphisms association with breast cancer risk in pashtun women of Pakistan.

BACKGROUND: Single Nucleotide polymorphisms (SNPs) in MMP8 and MMP9 have been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check MMP8 (rs11225395) and MMP9 (rs3787268) polymorphism with breast cancer risk in the selected population. METHODS: This study, consisting of 300 breast cancer patients and 168 gender and age-matched healthy controls was subjected to confirm MMP8 and MMP9 polymorphisms. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using the T-ARMS-PCR protocol. RESULTS: Based on our study results, significant associations were observed between the MMP8 rs11225395 risk allele (G) and increased breast cancer risk, with the G allele frequency higher in patients (65%) compared to controls (51%) (OR = 1.752, 95% CI = 1.423-3.662, p = 0.002). Genotypes GG (OR = 4.218, p = 0.005) and AG (OR = 7.286, p = 0.0001) of MMP8 rs11225395 were also significantly associated with elevated breast cancer risk. Similarly, MMP9 rs3787268 exhibited a higher frequency of the risk allele (A) in breast cancer cases (81%) compared to controls (41%), correlating strongly with increased risk (OR = 6.320, p = 0.0001). Genotypes AA (OR = 14.500, p = 0.0001) and AG (OR = 2.429, p = 0.077) of MMP9 rs3787268 containing the risk allele showed significant associations with heightened breast cancer risk. Subgroup analyses based on age, disease progression, tumor size, and grade revealed noteworthy associations for both MMP8 rs11225395 and MMP9 rs3787268. MMP8 rs11225395 genotypes displayed significant correlations with age (p = 0.066), disease progression (p = 0.0001), larger tumor size (p = 0.005), and higher tumor grade (p = 0.006). Similarly, MMP9 rs3787268 genotypes were significantly associated with age (p = 0.001), disease progression (p = 0.010), larger tumor size (p = 0.018), and higher tumor grade (p = 0.037). Logistic regression analyses further underscored these genetic variants' potential role as biomarkers in breast cancer, particularly in relation to specific hormone receptor statuses such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity. CONCLUSION: The results revealed significant associations between the mutant alleles and genotypes of MMP8 (rs11225395) and MMP9 (rs3787268) with increased breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

Portable noninvasive technologies for early breast cancer detection: A systematic review.

Breast cancer remains a leading cause of cancer mortality worldwide, with early detection crucial for improving outcomes. This systematic review evaluates recent advances in portable non-invasive technologies for early breast cancer detection, assessing their methods, performance, and potential for clinical implementation. A comprehensive literature search was conducted across major databases for relevant studies published between 2015 and 2024. Data on technology types, detection methods, and diagnostic performance were extracted and synthesized from 41 included studies. The review examined microwave imaging, electrical impedance tomography (EIT), thermography, bioimpedance spectroscopy (BIS), and pressure sensing technologies. Microwave imaging and EIT showed the most promise, with some studies reporting sensitivities and specificities over 90 %. However, most technologies are still in early stages of development with limited large-scale clinical validation. These innovations could complement existing gold standards, potentially improving screening rates and outcomes, especially in underserved populations, whiles decreasing screening waiting times in developed countries. Further research is therefore needed to validate their clinical efficacy, address implementation challenges, and assess their impact on patient outcomes before widespread adoption can be recommended.

Predictors of mastectomy in breast cancer patients with complete remission of primary tumor after neoadjuvant therapy: A retrospective study.

INTRODUCTION: Neoadjuvant therapy (NAT) should increase the rate of breast-conserving surgery (BCS) in non-metastatic breast cancer (BC) patients, especially in those achieving tumor shrinkage. Still, the conversion from a pre-planned mastectomy to BCS in patients responding to NAT is not a widespread standard. We aimed to identify factors influencing surgical choices in this setting. MATERIALS AND METHODS: We retrospectively collected data of BC patients with complete remission of primitive tumor (ypT0) after NAT, treated with BCS or mastectomy in two Italian breast units. Predictors of mastectomy were explored using logistic regression. Distant recurrence and event-free survival were assessed in the BCS and mastectomy cohort. RESULTS: 243 patients were included, 147 (60.5 %) treated with BCS and 96 (39.5 %) treated with mastectomy. In the mastectomy group, there were more centrally-located, multiple and larger tumors. At univariate regression analysis, central location, baseline tumor extension on ultrasound (US) and magnetic resonance imaging (MRI), multiple foci and clinical stage were significantly associated with the chance of receiving mastectomy. At multivariate analysis, only baseline focality on US and extension on MRI retained significance as predictors of mastectomy. Distant recurrence and event-free survival were significantly longer in patients undergoing BCS. CONCLUSION: Baseline tumor extension and focality were the main predictors of mastectomy in patients with ypT0 after NAT. However, BCS did not negatively affect survival outcomes in our cohort. An effort should be made to avoid potentially unnecessary mastectomy in this population, aiming at minimizing surgery-associated toxicities and improving patients' quality of life.

Breast-cancer specific comprehensive archive of Patient-Reported Outcome Measures (PROMs) for clinical research and clinical practice in oncology: Results from the PRO4All project.

BACKGROUND: Inclusion of patient-reported outcomes (PROs) in oncology clinical trials is strongly recommended. However, selecting the most appropriate patient-reported outcome measures (PROMs) is not easy. This study aimed to develop a breast cancer (BC) specific comprehensive archive of PROMs. METHODS: As part of the PRO4All project, we identified available PROMs in oncology by searching facit.org, eortc.org, eprovide.mapi-trust.org, PubMed, ema.europa.eu (European Public Assessment Reports) and published reviews. For this analysis, only BC tools were extracted. We described information about PROM name, type of questionnaire, questionnaire variant(s), recall period, number of items, and presence of minimum clinically important difference (MCID) reference in literature. Then, we assigned each item to a specific domain according to a predefined taxonomy of 38 items for outcome classification. RESULTS: We identified and analyzed 383 PROMs. Of these, 29 were BC specific, but 2 were excluded because the questionnaires description was not available. 6 (22.2 %) were variants of another questionnaire. All questionnaires were self-reported. In 6 cases (22.2 %) the recall period to consider was the "last week". The mean number of items per questionnaire was 25.81 (range 6-71). 602 items were assigned to an outcome domain: emotional functioning/wellbeing in 26.6 % of cases, physical functioning in 14.1 %, delivery of care in 10.8 %, and general outcomes in 10.5 %. MCID reference was found only in 4 (14.8 %) cases. CONCLUSIONS: The newly developed archive represents a useful tool to optimize the use of PROMs in the evaluation of treatments in BC patients, promoting a patient-centered approach both in clinical research and practice.

Sexuality after breast cancer treatment: A physician's survey of current clinical practice.

BACKGROUND: Side effects of breast cancer treatment (BCT) impact patients' general and sexual wellbeing. Sexuality related complaints are reported by 70% of breast cancer survivors mainly due to the genitourinary syndrome of menopause (GSM). In clinical care, sexual side effects are often un(der)detected because physicians as well as patients experience barriers to discuss sexuality-related issues. MATERIALS AND METHODS: We composed an online survey ourselves using known definitions about sexuality and menopause and known factors for not discussing sexuality. We used multiple-choice questions with a Likert scale to optimize interpretation of the statements. 64 practitioners completed the survey. With this online survey, we examined physicians' knowledge of -and attitude towards- sexual wellbeing and detection and treatment of GSM in breast cancer survivors (BCS). RESULTS: Vaginal dryness and dyspareunia were the symptoms most associated with menopause (n = 63/64 (98 %) and n = 56/64 (87 %)) and sexuality (n = 63/64 (98 %) and n = 61/64 (95 %)). These 2 complaints were also the most discussed symptoms of menopause (vaginal dryness n = 51/64 (80 %) and dyspareunia n = 45/64 (70 %)). The main reason to not discuss these issues were absence of reporting GSM (n = 40/64 (62 %)) and absence of a direct cause to discuss GSM (n = 35/64 (55 %). 64 % (n = 41/64) of practitioners don't feel sufficiently educated to discuss and treat GSM. They proposed vaginal estrogens to treat GSM as first or second line respectively in 12 % (n = 8/64) and 46 % (n = 30/64) of symptomatic BCS. DISCUSSION: Although sexuality related complaints are common in BCS, 64% of all participating physicians feel they are not adequately trained to handle them. More attention towards training of physicians is needed to discuss GSM related complaints also when they are not spontaneously reported by a patient and with clear guidance towards the medical treatment of GSM in BCS.

Risk factors behind the increase of early-onset cancer in Italian adolescents and young adults: An investigation from the Italian AYA Working group.

The incidence of early-onset cancers in adolescents and young adults (AYA) has been increasing worldwide since the 1990s. In Italy, a significant increased rate of 1.6 % per year has been reported for early-onset cancers among females between 2008 and 2016. This is mainly attributable to melanoma, thyroid, breast and endometrial cancer. The aim of our work was to describe temporal trends of the main established lifestyle risk factors (tobacco use, alcohol consumption, obesity, physical inactivity, dietary westernization and reproductive factors) over the last 20 years in the Italian AYA population. Available data on behavioural risk factors, individual and household daily life have been obtained and elaborated from PASSI, ISTAT and Eurostat reports. Lowering age of smoking initiation, an increase in alcohol drinkers among young females, and an obesity and overweight epidemic, particularly among children and adolescents as a result of physical inactivity and dietary habits, may be contributing factors behind this cancer epidemic, especially among females. In-depth investigations are needed to understand the exact role of each contributing factor, the effects of exposure to nicotine-containing products and environmental factors such as endocrine disruptors that could play a role in this phenomenon.

Synergic effects of DL-limonene, R-limonene, and cisplatin on AKT, PI3K, and mTOR gene expression in MDA-MB-231 and 5637 cell lines.

The anticancer and cytotoxic effects of DL-Limonene and R-Limonene are well-documented. However, the role of natural compounds in enhancing the efficacy of platinum-based drugs like Cisplatin (CisPt) remains debated. This study aims to boost Cisplatin's impact on breast (MDA-MB-231) and bladder (5637) cancer cells using DL-Limonene and R-Limonene. Different concentrations of DL-Limonene, R-Limonene, and Cisplatin, combined, were used to treat MDA-MB-231 and 5637 cells in this experimental study. The cell's viability was evaluated using an MTT assay. AnnexinV- PI staining was applied to evaluate the percentage of apoptotic cells. Cytotoxicity results showed that combining DL-Limonene, R-Limonene, and Cisplatin significantly improved outcomes in MDA-MB-231 cells (P < 0.05). Annexin/PI staining revealed apoptosis rates of 74 %, 28 %, 43 %, 81 %, and 91 % for Cisplatin40, R-Limonen1000, DL-Limonen1000, R-Limonen1000/DL-Limonen1000, and the combined treatment, respectively, versus 13 % in the control. The combination also resulted in the greatest reduction of AKT, PI3K, and mTOR gene expression. Our results show that R-Limonene and DL-Limonene enhance Cisplatin's cancer-inhibiting effects in breast and bladder cancer cell lines. These compounds may be promising for combination therapy, potentially allowing for lower doses of chemotherapy and reducing side effects like nephrotoxicity.

Impact of 18F-FES PET/CT on Clinical Decisions in the Management of Recurrent or Metastatic Breast Cancer.

The clinical impact of 16α-18F-fluoro-17ß-estradiol (18F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor-positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18F-FES PET/CT. In 139 (40%) patients,18F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18F-FES-negative (44% [36/81]) than 18F-FES-positive (30% [51/172]) or mixed 18F-FES-positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice.

Unveiling the comorbidity burden of male breast cancer.

Male breast cancer (MBC) is a rare condition with unique characteristics compared to female breast cancer (FBC). Despite its scarceness, there is growing evidence that MBC should not be studied and treated as FBC due to factors like later diagnosis stage and distinct genetic makeup. Retrospective observational study in the EpiChron Cohort, selecting all the prevalent patients with breast cancer between 2010 and 2019. Logistic models were used to determine associated comorbidities. Between 2010 and 2019, 105 MBC and 11,657 FBC patients were found in the EpiChron Cohort. MBC patients had a high mean age at diagnosis and number of comorbidities. Paying attention to comorbidity prevalences in breast cancer patients, it was clear that MBC patients tended to be prone to cardio-metabolic coexisting diseases, while FBC patients were more prone to hormone-, bone- and mental diseases. There were nine chronic conditions associated to MBC patients, but after a year-by-birth matching only four associations remained. Two of them were associated previously [odds ratio (95% confidence interval)]: "Disorder of lipid metabolism" [1.65 (1.03-2.64)] and "Genitourinary symptoms and ill-defined conditions" [2.03 (1.07-3.87)]; and the other two were new, "Anxiety disorders" [2.05 (1.09-3.87)] and "Osteoporosis" [3.58 (1.26-10.14)]. After comparing associated comorbidities in FBC with those in MBC, it seems MBC patients share some of them, but they have their own particular set of coexisting diseases. In fact, once a year-by-birth matching was performed in MBC patient cohort, it was more obvious MBC comorbidities behave more similar to none-Breast-Cancer male population than to FBC patients. These findings highlight the distinct characteristics of the MBC patient population and the need for a tailored approach of managing MBC.

Cystathionine-γ-lyase contributes to tamoxifen resistance, and the compound I194496 alleviates this effect by inhibiting the PPARγ/ACSL1/STAT3 signalling pathway in oestrogen receptor-positive breast cancer.

Tamoxifen (TAM) resistance is a major challenge in treating oestrogen receptor-positive (ER+) breast cancers. It is possible that the H2S synthase cystathionine-γ-lyase (CSE), which has been previously shown to promote tumour growth and metastasis in other cancer cells, is involved in this resistance. Therefore, we investigated CSE's role and potential mechanisms in TAM-resistant breast cancer cells. First, we examined the effect of CSE expression on TAM sensitivity and resistance in MCF7 (breast cancer) cells. The findings revealed that CSE was directly associated with TAM sensitivity and involved in TAM resistance in ER+ breast cancer cells, indicating that it may be useful as a biomarker. Next, we wanted to determine the molecular mechanism of CSE's role in TAM resistance. Using cell migration, co-immunoprecipitation, western blotting, and cell viability assays, we determined that the CSE/H2S system can affect the expression of PPARγ by promoting the sulfhydrylation of PPARγ, which regulates the transcriptional activity of ACSL1. ACSL1, in turn, influences STAT3 activation by affecting the phosphorylation, palmitoylation and dimerization of STAT3, ultimately leading to the development of TAM resistance in breast cancer. Finally, we examined the effect of CSE inhibitors on reducing drug resistance to determine whether CSE may be used as a biomarker of TAM resistance. We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.

Interval breast cancer rates for tomosynthesis vs mammography population screening: a systematic review and meta-analysis of prospective studies.

OBJECTIVES: We aimed to synthesise evidence from prospective studies of digital breast tomosynthesis (DBT) screening to assess its effectiveness compared to digital mammography (DM). Specifically, we examined whether DBT reduces interval cancer rates (ICRs) in population breast cancer screening. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of DBT screening studies (identified from January 2013 to March 2024). We included both RCTs and non-randomised prospective studies that used an independent comparison for our primary outcome ICRs. The risk of bias was assessed with QUADAS-2. We compared the ICR, cancer detection rate (CDR), and recall rate of DBT and DM screening using random effects meta-analysis models. Subgroup analyses estimated outcomes by study design. Sensitivity analyses estimated absolute effects from relative effects. RESULTS: Ten prospective studies (three RCTs, seven non-randomised) were eligible; all had a low risk of bias. There were 205,245 DBT-screened and 306,476 DM-screened participants with follow-up for interval cancer data. The pooled absolute ICR did not significantly differ between DBT and DM: -2.92 per 10,000 screens (95% CI: -6.39 to 0.54); however subsequent subgroup analysis indicated certain study designs may have biased this ICR estimate. Pooled ICR from studies that only sampled groups from the same time and region indicated DBT led to 5.50 less IC per 10,000 screens (95% CI: -9.47 to -1.54). Estimates from subgroup analysis that compared randomised and non-randomised trials did not significantly differ. CONCLUSION: This meta-analysis provides suggestive evidence that DBT decreases ICR relative to DM screening; further evidence is needed to reduce uncertainty regarding ICR differences between DBT and DM. KEY POINTS: Question Does DBT have long-term benefits over standard DM? Finding We find suggestive evidence in our primary analysis and stronger evidence in a follow-up analysis that DBT reduces interval cancers. Clinical relevance This meta-analysis provides the first indication that DBT may detect additional cancers that are clinically meaningful, based on suggestive evidence of a reduction in ICR. This finding does not preclude the simultaneous possibility of overdiagnosis.

Diagnostic performance of TILs-US score and LPBC in biopsy specimens for predicting pathological complete response in patients with breast cancer.

BACKGROUND: Tumor-infiltrating lymphocytes-ultrasonography (TILs-US) score is used to predict lymphocyte-predominant breast cancer (LPBC) in surgical specimens. We aimed to compare diagnostic performance of TILs-US score for predicting pathological complete response (pCR) with that of LPBC in biopsy specimens. METHODS: TILs ≥ 50% in biopsy specimens was defined as biopsy-LPBC, and TILs-US score ≥ 4 was categorized as TILs-US score-high. Basic nomogram for pCR was developed using stepwise logistic regression based on the smallest Akaike Information Criterion, and biopsy-LPBC and TILs-US score nomograms were developed by integrating biopsy-LPBC or TILs-US scores into a basic nomogram. The diagnostic performance of the nomograms for pCR was compared using area under the curve (AUC), categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: This retrospective study evaluated 118 patients with breast cancer, including 33 (28.0%) with biopsy-LPBC, 52 (44.1%) with TILs-US score-high, with 34 (28.8%) achieving pCR. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and AUC for predicting pCR were 0.53, 0.82, 2.96, 0.57, and 0.68, respectively, for biopsy-LPBC, and 0.76, 0.69, 2.47, 0.34, and 0.73, respectively, for TILs-US score. The biopsy-LPBC nomogram showed significant improvements in categorical NRI (p = 0.023) and IDI (p = 0.007) but not in AUC (p = 0.25), compared with the basic nomogram. The TILs-US nomogram exhibited significant improvements in AUC (p = 0.039), categorical NRI (p = 0.010), and IDI (p < 0.001). CONCLUSIONS: The TILs-US score may serve as a novel marker for prediction of pCR in patients with breast cancer. An external validation study is warranted to confirm our findings.

Association between dietary factors and breast cancer risk: a matched case-control study in Vietnam.

BACKGROUND: The role of diet in breast cancer prevention is controversial and limited in low-middle-income countries (LMICs). This study aimed to investigate the association between different dietary factors and breast cancer risk in Vietnamese women. METHODS: Three hundred seventy newly histologically confirmed breast cancer cases and 370 controls matched by 5-year age from September 2019 to March 2020 in Ho Chi Minh City were recorded dietary intake using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated using conditional logistic regression and adjusted with potential confounders. RESULTS: Compared to the lowest quartile of intake, we found that the highest intake of vegetables, fruit, soybean products, coffee, and egg significantly decreased breast cancer risk, including dark green vegetables (OR 0.46, 95% CI 0.27-0.78, ptrend=0.022), legumes (OR 0.19, 95% CI 0.08-0.44, ptrend <0.001), starchy vegetables (OR 0.37, 95% CI 0.21-0.66, ptrend=0.003), other vegetables (OR 0.46, 95% CI 0.28-0.77, ptrend=0.106), fruits (OR 0.44, 95% CI 0.26-0.74, ptrend <0.001), soybean product (OR 0.45, 95% CI 0.24-0.86, ptrend=0.311), coffee (OR 0.47, 95% CI 0.23-0.95, ptrend 0.004), and egg (OR 0.4, 95% CI 0.23-0.71, ptrend=0.002). CONCLUSION: Greater consumption of vegetables, fruit, soybean products, coffee, and eggs is associated with a lower risk of breast cancer. This study provides evidence of breast cancer prevention by increasing the intake of these dietary groups, especially in LMICs.

Effect of ultrasound combined with highland barley dietary fiber on gel properties of reduced-salt chicken breast myofibrillar protein.

This study aimed to investigate the effect of ultrasound combined with highland barley dietary fiber (HBDF) on the quality of reduced-salt chicken breast myofibrillar protein (MP) gel. The molecular forces maintaining gel structure, the gelling formation process, and gel microstructure of different groups, two control groups (2% sodium chloride [NaCl] group, 1% NaCl group), and four treatment groups (0.3% HBDF+U5, 0.3% HBDF+U10, 0.5% HBDF+U5, and 0.5% HBDF+U10) were examined. Results indicated significant improvements (p < 0.05) in gel properties such as water-holding capacity, textural characteristics, and color of the MP gel of the four treatment groups compared to Control 2 (1% NaCl) group. Furthermore, the second structural alterations were characterized by increase ß-sheet, ß-turn, and random coil structure contents in treatment groups, especially in 0.3% HBDF+U5 and 0.5% HBDF+U5 groups; in addition, the exposure of more hydrophobic groups and the formation of disulfide bonds and hydrogen bonds were promoted in treatment groups, thus enhancing protein aggregation and gel quality. Finally, compared to Control 2 (1% NaCl) group, more compact and uniform gel network structures and pores inside the composite gels were observed in treatment groups. In conclusion, the findings demonstrated that the application of ultrasound in combination with HBDF improved the gelling characteristics of reduced-salt chicken breast MP gel, especially 0.3% HBDF+U5 and 0.5% HBDF+U5 groups.