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1.
Breast Cancer Res ; 26(1): 110, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961497

ABSTRACT

Breast cancer (BC) is a highly prevalent malignancy worldwide, with complex pathogenesis and treatment challenges. Research reveals that methyltransferase-like 3 (METTL3) is widely involved in the pathogenesis of several tumors through methylation of its target RNAs, and its role and mechanisms in BC are also extensively studied. In this review, we aim to provide a comprehensive interpretation of available studies and elucidate the relationship between METTL3 and BC. This review suggests that high levels of METTL3 are associated with the pathogenesis, poor prognosis, and drug resistance of BC, suggesting METTL3 as a potential diagnostic or prognostic biomarker and therapeutic target. Collectively, this review provides a comprehensive understanding of how METTL3 functions through RNA methylation, which provides a valuable reference for future fundamental studies and clinical applications.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Methyltransferases , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Drug Resistance, Neoplasm/genetics , Methyltransferases/metabolism , Methyltransferases/genetics , Methyltransferases/antagonists & inhibitors , Biomarkers, Tumor/metabolism , Prognosis , Molecular Targeted Therapy , Animals
2.
Algorithms ; 17(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38962581

ABSTRACT

Breast cancer is the most common cancer affecting women globally. Despite the significant impact of deep learning models on breast cancer diagnosis and treatment, achieving fairness or equitable outcomes across diverse populations remains a challenge when some demographic groups are underrepresented in the training data. We quantified the bias of models trained to predict breast cancer stage from a dataset consisting of 1000 biopsies from 842 patients provided by AIM-Ahead (Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity). Notably, the majority of data (over 70%) were from White patients. We found that prior to post-processing adjustments, all deep learning models we trained consistently performed better for White patients than for non-White patients. After model calibration, we observed mixed results, with only some models demonstrating improved performance. This work provides a case study of bias in breast cancer medical imaging models and highlights the challenges in using post-processing to attempt to achieve fairness.

3.
Environ Pollut ; 358: 124495, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964647

ABSTRACT

Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/HER2-, HER2+ or HR-/HER2-. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk.

4.
Front Oncol ; 14: 1364397, 2024.
Article in English | MEDLINE | ID: mdl-38966067

ABSTRACT

Background and aim: This study aims to analyze the worldwide prevalence, mortality rates, and disability-adjusted life years (DALYs) attributed to breast cancer in women between 1990 and 2019. Additionally, it seeks to forecast the future trends of these indicators related to the burden of breast cancer in women from 2020 to 2030. Methods: Data from the Global Burden of Disease Study (GBD) 2019 was analyzed to determine the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of DALYs due to breast cancer in women across 204 countries and territories from 1990 to 2019. Socio-economic development levels of countries and regions were assessed using Socio-demographic Indexes, and trends in the burden of breast cancer in women worldwide from 2020 to 2030 were projected using generalized additive models (GAMs). Results: The estimated annual percentage change (EAPC) in the ASIR breast cancer in women globally was 0.36 from 1990 to 2019 and is expected to increase to 0.44 from 2020 to 2030. In 2019, the ASIR of breast cancer in women worldwide was 45.86 and is projected to reach 48.09 by 2030. The burden of breast cancer in women generally rises with age, with the highest burden expected in the 45-49 age group from 2020 to 2030. The fastest increase in burden is anticipated in Central sub-Saharan Africa (EAPC in the age-standardized death rate: 1.62, EAPC in the age-standardized DALY rate: 1.52), with the Solomon Islands (EAPC in the ASIR: 7.25) and China (EAPC in the ASIR: 2.83) projected to experience significant increases. Furthermore, a strong positive correlation was found between the ASIR breast cancer in women globally in 1990 and the projected rates for 2030 (r = 0.62). Conclusion: The anticipated increase in the ASIR of breast cancer in women globally by 2030 highlights the importance of focusing on women aged 45-49 in Central sub-Saharan Africa, Oceania, the Solomon Islands, and China. Initiatives such as breast cancer information registries, raising awareness of risk factors and incidence, and implementing universal screening programs and diagnostic tests are essential in reducing the burden of breast cancer and its associated morbidity and mortality.

5.
Explor Target Antitumor Ther ; 5(3): 678-698, 2024.
Article in English | MEDLINE | ID: mdl-38966174

ABSTRACT

Breast cancer (BC) is the most prevalent malignancy affecting women worldwide, including Portugal. While the majority of BC cases are sporadic, hereditary forms account for 5-10% of cases. The most common inherited mutations associated with BC are germline mutations in the BReast CAncer (BRCA) 1/2 gene (gBRCA1/2). They are found in approximately 5-6% of BC patients and are inherited in an autosomal dominant manner, primarily affecting younger women. Pathogenic variants within BRCA1/2 genes elevate the risk of both breast and ovarian cancers and give rise to distinct clinical phenotypes. BRCA proteins play a key role in maintaining genome integrity by facilitating the repair of double-strand breaks through the homologous recombination (HR) pathway. Therefore, any mutation that impairs the function of BRCA proteins can result in the accumulation of DNA damage, genomic instability, and potentially contribute to cancer development and progression. Testing for gBRCA1/2 status is relevant for treatment planning, as it can provide insights into the likely response to therapy involving platinum-based chemotherapy and poly[adenosine diphosphate (ADP)-ribose] polymerase inhibitors (PARPi). The aim of this review was to investigate the impact of HR deficiency in BC, focusing on BRCA mutations and their impact on the modulation of responses to platinum and PARPi therapy, and to share the experience of Unidade Local de Saúde Santa Maria in the management of metastatic BC patients with DNA damage targeted therapy, including those with the Portuguese c.156_157insAlu BRCA2 founder mutation.

6.
Explor Target Antitumor Ther ; 5(3): 551-567, 2024.
Article in English | MEDLINE | ID: mdl-38966180

ABSTRACT

Aim: To investigate the molecular effects of a novel combination [sertraline and plumbagin (comb) with ormeloxifene (Orm)] for anticancer activity in triple negative breast cancer cell line "MDA-MB-231". Methods: The cytotoxic effect of the drugs was analyzed by the MTT assay and nuclear morphological changes by acridine orange/ethidium bromide (AO/EB) staining. Induction of apoptosis by annexin V-FITC staining, active caspase-3 detection and cell cycle analysis were studied in vitro on "MDA-MB-231" cells. The qRT-PCR was done to explore the upregulation and down regulation of targeted genes for angiogenesis, metastasis, tumor suppression and protein folding on the triple negative breast cancer cells. The preliminary anti-angiogenic effect of the drugs was assessed by chorioallantoic membrane (CAM) assay. Results: Orm showed inhibitory effects in "MDA-MB-231" cells in a dose and time dependent manner whereas; the drugs in combination gave better cytotoxic effects in the screening MTT assay. Orm + comb was more effective than Orm alone in eliciting apoptosis as well as inhibited the single cell to grow into a colony. CAM assay using Orm and Orm + comb suggested the anti-angiogenic potential which was further confirmed by the downregulation of VEGF in "MDA-MB-231" cells by qRT-PCR studies. The combination was found to effectively upregulate the expression of P53 and P21 and downregulate the gene expression of zinc finger E-box binding homeobox 1 (ZEB1) and heat shock protein 70 (HSP70) in "MDA-MB-231" cancer cells. Conclusions: Collectively this study reveals the efficacy of Orm + comb as more significant than the clinically used tamoxifen (Tam). The study elucidates the promising novelty of the combination as a potential chemotherapeutic intervention for mitigating the aggressiveness of triple negative breast cancer and it addresses the intrinsic resistance caused by single drug treatments.

7.
Explor Target Antitumor Ther ; 5(3): 522-542, 2024.
Article in English | MEDLINE | ID: mdl-38966182

ABSTRACT

Aim: Metal nanoclusters are emerging nanomaterials applicable for drug delivery. Here, the toxicity and oxidative stress induction of divalent cationic cadmium (Cd2+) was compared with a Cd in the form of nanocluster. Then, it was used for targeted drug delivery into breast cancer cell lines. Methods: Using a green chemistry route, a Cd nanocluster (Cd-NC) was synthesized based on bovine serum albumin. After characterization, its genotoxicity and oxidative stress induction were studied in both in vitro and in vivo. After that, it was conjugated with hyaluronic acid (HA). The efficiency of hyaloronized-Cd-CN (HA-Cd-NC) for loading and releasing crocin (Cro), an anticancer phytochemical, was studied. Finally, it was applied for cell death induction in a panel of breast cancer cell lines. Results: The comet assay results indicated that, unlike Cd2+ and potassium permanganate (KMnO4), no genotoxicity and oxidative stress was induced by Cd-NC in vitro. Then, the pharmacokinetics of this Cd-NC was studied in vivo. The data showed that Cd-NC has accumulated in the liver and excreted from the feces of mice. Unlike Cd2+, no toxicity and oxidative stress were induced by this Cd-NC in animal tissues. Then, the Cd-NC was targeted toward breast cancer cells by adding HA, a ligand for the CD44 cell surface receptor. After that, Cro was loaded on HA-Cd-NC and it was used for the treatment of a panel of human breast cancer cell lines with varying degrees of CD44. The half-maximal drug inhibitory concentration (IC50) of Cro was significantly decreased when it was loaded on HA-Cd-NC, especially in MDA-MB-468 with a higher degree of CD44 at the surface. These results indicate the higher toxicity of Cro toward breast cancers when carried out by HA-Cd-NC. Conclusions: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.

8.
Cureus ; 16(6): e61625, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38966461

ABSTRACT

INTRODUCTION: Improved breast cancer treatments have increased survival rates, but prolonged and costly therapies strain survivors financially. This study addresses the dearth of research on financial difficulties among breast cancer survivors (BCS) in India. METHODS: A mixed-methods study was employed; we assessed financial hardship (FH) using the Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT), a validated 12-item questionnaire. The minimum score represents FH (FH was categorized based on scores <27). RESULTS: Out of 80 surveyed BCS, 60% experienced FH and had a median age of 48 years (40.5-56.5 years). Factors such as occupation, education, income, expenditures, insurance coverage, and impact on savings exhibited significant associations with FH. With only one-third having health insurance and 43.8% self-funding treatment, this research sheds light on the urgent need for targeted support and policies to alleviate the financial burdens faced by BCS in the Indian context. CONCLUSION: Financial hardship harms the mental and physical health of BCS. Collaborative efforts among policymakers, healthcare professionals, and insurers are crucial to establishing a compassionate healthcare system that addresses both immediate health and long-term financial concerns.

9.
Front Med (Lausanne) ; 11: 1418800, 2024.
Article in English | MEDLINE | ID: mdl-38966532

ABSTRACT

Background: Potential uncertainties and overtreatment exist in adjuvant chemotherapy for triple-negative breast cancer (TNBC) patients. Objectives: This study aims to explore the performance of deep learning (DL) models in personalized chemotherapy selection and quantify the impact of baseline characteristics on treatment efficacy. Methods: Patients who received treatment recommended by models were compared to those who did not. Overall survival for treatment according to model recommendations was the primary outcome. To mitigate bias, inverse probability treatment weighting (IPTW) was employed. A mixed-effect multivariate linear regression was employed to visualize the influence of certain baseline features of patients on chemotherapy selection. Results: A total of 10,070 female TNBC patients met the inclusion criteria. Treatment according to Self-Normalizing Balanced (SNB) individual treatment effect for survival data model recommendations was associated with a survival benefit (IPTW-adjusted hazard ratio: 0.53, 95% CI, 0.32-8.60; IPTW-adjusted risk difference: 12.90, 95% CI, 6.99-19.01; IPTW-adjusted the difference in restricted mean survival time: 5.54, 95% CI, 1.36-8.61), which surpassed other models and the National Comprehensive Cancer Network guidelines. No survival benefit for chemotherapy was seen for patients not recommended to receive this treatment. SNB predicted older patients with larger tumors and more positive lymph nodes are the optimal candidates for chemotherapy. Conclusion: These findings suggest that the SNB model may identify patients with TNBC who could benefit from chemotherapy. This novel analytical approach may provide debiased individual survival information and treatment recommendations. Further research is required to validate these models in clinical settings with more features and outcome measurements.

10.
Oncol Lett ; 28(2): 389, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38966584

ABSTRACT

The present study aimed to investigate whether local recurrence (LR) after nipple-sparing mastectomy (NSM) and reconstruction was associated with i) Ki67 values and molecular subtypes of the initial lesions, and ii) the size of the initial tumor and the size of the implant. A total of 156 patients with breast cancer with a mean age of 51.58 years (age range, 26-75 years) who underwent NSM with primary implant breast reconstruction were analyzed. After surgery, the mean follow-up time was 59.26 months (range, 17-85 months). Molecular subtypes, Ki67 values, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were recorded for each patient. Additionally, information regarding the size of the implant and the initial tumor size were collected. The information was used to assess LR. For univariate analyses of risk factors, χ2 test, Fisher's exact test, Mann-Whitney U test and Student's t-test for independent samples were used. For multivariate analyses, a Cox proportional-hazards model was used. NSM was the primary treatment for breast cancer in 34/156 patients (21.8%), while 122/156 (78.2%) of patients received neoadjuvant chemotherapy followed by surgery. Luminal B was the most frequent molecular subtype, detected in 82/156 patients (52.6%), whereas the luminal A subtype was detected in 37 patients (23.7%) and the HER2-enriched subtype was detected in 17/156 patients (10.9%). Ki67 expression was low in 13/156 patients (8.3%), while medium expression was detected in 78/156 patients (50.0%) and high expression was present in 58/156 patients (37.2%). LR was noted in 17/156 patients (10.9%). As determined by univariate analysis, lower ER (P=0.010) and PR (P=0.008) expression were indicated to be significant risk factors for LR. In conclusion, in the present patient cohort, low ER and PR expression were risk factors for LR of breast cancer, whereas Ki67 status and molecular subtype were not statistically significant risk factors for LR. Additionally, the size of the initial tumor and the size of the implant were not risk factors for LR. These findings are consistent with the current literature, and should be utilized when discussing treatment options and potential clinical outcomes with patients prior to surgical management.

11.
Oncol Lett ; 28(2): 390, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38966583

ABSTRACT

Continued advances in the diagnosis and treatment of breast cancer (BC) have led to an increase in the number of long-term BC survivors and an increase in the incidence of metachronous BC in the contralateral breast. Therefore, it is important to understand the factors that influence the development of metachronous BC; however, the impact of the laterality of the initial ipsilateral (I)BC as a risk factor for the development of metachronous contralateral (MC)BC has not been extensively investigated. The present study included 17,082 female patients with stage 0-3 IBC from the prospectively maintained Korean Breast Cancer Registry from 1989-2013 and divided them into two groups: Patients with MCBC (n=88) and those without MCBC (n=16,994). Risk factors that present at the initial BC diagnosis that could significantly influence the development of MCBC were screened for and risks were evaluated using the Fine-Gray subdistribution hazard model. Significant differences in baseline characteristics between MCBC and non-MCBC groups were demonstrated. Patients aged <40 years, those with histological and nuclear grade 3 tumors, and those with the triple-negative BC subtype were significantly more prevalent in the MCBC group than in the non-MCBC group. Additionally, the cumulative incidence of MCBC increased over time, with a notable increase from 0.1% in year 1 to 1.6% in year 10. Survival analysis revealed no significant differences in overall or BC-specific survival between the two groups. Key predictive factors identified for MCBC included an age of <40 years at initial diagnosis, a negative progesterone receptor status, and a Ki-67 score of >14%. Overall, the present study revealed several factors associated with MCBC and emphasized the need for long-term monitoring of BC survivors, considering these newly identified risk factors.

12.
Acta Med Philipp ; 58(3): 70-75, 2024.
Article in English | MEDLINE | ID: mdl-38966846

ABSTRACT

This is a case report of a 76-year-old Filipino male who presented with a six-year history of a steadily growing left breast mass. The mass was eventually diagnosed to be Invasive Ductal Carcinoma, Anatomic and Prognostic Stage IIIB (T4b cN0 M0), Grade 3, Luminal A. Subsequently, the patient underwent neoadjuvant chemotherapy of doxorubicin/cyclophosphamide and paclitaxel, followed by modified radical mastectomy with axillary lymph node dissection, concluded by post-mastectomy radiation therapy. The patient had complete clinical response to this trimodality therapy. The rarity of this case is juxtaposed and integrated with the present literature on male breast cancer.

13.
Breast Dis ; 43(1): 223-229, 2024.
Article in English | MEDLINE | ID: mdl-38968038

ABSTRACT

BACKGROUND: Neuro-Behcet's disease (NBD) is a variant of Behcet's disease (BD). To our knowledge, there have been no previous reports on concurrent NBD in breast cancer patients undergoing chemotherapy. CASE PRESENTATION: Our patient had a history of BD and was asymptomatic. She was diagnosed with human epidermal growth factor receptor 2-positive breast cancer by core needle biopsy and was administered neoadjuvant chemotherapy. After four courses, in addition to the aggravation of the existing adverse events, headache, fever, dysarthria, and muscle weakness in the upper left and lower extremities appeared. On admission, she was diagnosed with acute NBD, and steroid therapy was initiated. After her symptoms improved gradually, she was discharged. Then, she underwent mastectomy and axillary lymph node dissection for breast cancer. Trastuzumab and pertuzumab plus tamoxifen were administered postoperatively. Two years postoperatively, no recurrence of breast cancer and NBD was noted. CONCLUSION: When chemotherapy is administered to breast cancer patients with a history of BD, it is necessary to select chemotherapy with as few adverse events as possible and to continue with treatment while paying attention to the risk of NBD.


Subject(s)
Behcet Syndrome , Breast Neoplasms , Neoadjuvant Therapy , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/drug therapy , Behcet Syndrome/complications , Behcet Syndrome/drug therapy , Receptor, ErbB-2/metabolism , Mastectomy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Trastuzumab/therapeutic use , Trastuzumab/adverse effects , Middle Aged , Tamoxifen/therapeutic use , Tamoxifen/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Adult
14.
Breast Dis ; 43(1): 231-236, 2024.
Article in English | MEDLINE | ID: mdl-38968039

ABSTRACT

Phyllodes tumor is an uncommon breast neoplasm that is present in variable sizes. Giant phyllodes are those larger than 10 cm in diameter. Clinically, giant phyllodes tumors present as a visible, rapidly growing mass distorting the breast contour. Such tumors with large size and rapid growth rate suggest a phyllode diagnosis of fibroadenoma. Planning a standard treatment strategy for these tumors is quite challenging. While adequate surgical excision with tumor-free resection margins is the standard of care for most giant phyllodes cases, borderline and malignant giant phyllodes tumors might require wider resections given their high recurrence rates. Some authors described total mastectomy as the treatment option for giant borderline and malignant phyllodes to obtain wide, clear margins. Between March 2022 and September 2023, our surgical oncology department presented and operated on three cases of giant phyllodes. They underwent a nipple-sparing mastectomy and immediate breast reconstruction using pre-pectoral silicone implants. We think that with such a procedure, we can benefit from the wide, safe margins of mastectomy that have been proven to decrease local recurrence rates while considering the aesthetic outcome.


Subject(s)
Breast Neoplasms , Mammaplasty , Nipples , Phyllodes Tumor , Humans , Phyllodes Tumor/surgery , Phyllodes Tumor/pathology , Female , Breast Neoplasms/surgery , Adult , Mammaplasty/methods , Nipples/surgery , Middle Aged , Mastectomy , Breast Implants
15.
Talanta ; 278: 126481, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38968655

ABSTRACT

Quantitative microRNA (miRNA) detection is crucial for early breast cancer diagnosis and prognosis. However, quick and stable fluorescence sensing for miRNA identification is still challenging. This work developed a novel label-free detection method based on AuNPs etching for quantitatively detecting miRNA-155. A layer of AuNPs was grown on the surface of mesoporous silica nanoparticles (MSN) loaded with Rhodamine 6G (R6G) using seed-mediated growth, followed by probe attachment. In the presence of miRNA-155, the MSN@R6G@AuNP surface loses the protection of the attached probe, rendering AuNPs susceptible to etching by hydrochloric acid. This results in a significant fluorescent signal being released in the free space. The encapsulation with AuNPs effectively reduces signal leakage, while the rapid etching process shortens detection time. This strategy enables sensitive and fast detection with a detection range of 100 fM to 100 nM, a detection limit of 2.18 fM, and a detection time of 30 min. The recovery rate in normal human serum ranges from 99.02 % to 106.34 %. This work presents a simple biosensing strategy with significant potential for application in tumor diagnosis.

16.
Curr Probl Cancer ; 51: 101118, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38968834

ABSTRACT

To date, mounting evidence have shown that patients with multiple endocrine neoplasia type 1 (MEN1) may face an increased risk for breast carcinogenesis. The product of the MEN1 gene, menin, was also indicated to be an important regulator in breast cancer signaling network. Menin directly interacts with MLL, EZH2, JunD, NF-κB, PPARγ, VDR, Smad3, ß-catenin and ERα to modulate gene transcriptions leading to cell proliferation inhibition. Moreover, interaction of menin-FANCD2 contributes to the enhancement of BRCA1-mediated DNA repair mechanism. Ectopic expression of menin causes Bax-, Bak- and Caspase-8-dependent apoptosis. However, despite numbers of menin inhibitors were exploited in other cancers, data on the usage of menin inhibitors in breast cancer treatment remain limited. In this review, we focused on the menin associated signaling pathways and gene transcription regulations, with the aim of elucidating its molecular mechanisms and of guiding the development of novel menin targeted drugs in breast cancer therapy.

17.
Cancer Lett ; : 217102, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969157

ABSTRACT

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. Hypoxia-activated prodrugs (HAPs) have shown promise as potential therapeutic agents for TNBC. While increasing hypoxia levels may promote the HAP activation, it raises concerns regarding HIF1α-dependent drug resistance. It is desirable to develop a targeted approach that enhances tumor hypoxia for HAP activation without promoting HIF1α-dependent drug resistance in TNBC treatment. Herein, we proposed a multi-responsive carrier-free self-assembled nanomedicine named AQ4N@CA4T1ASO. This nanomedicine first targeted tumors by the TNBC-targeting aptamers (T1), and then disassembled in the reductive and acidic conditions within tumors. The released Combretastatin 4 (CA4) could exacerbate hypoxia, thereby promoting the conversion of inactive Banoxantrone (AQ4N) to its active form, AQ4. Simultaneously, the released antisense oligonucleotide (ASO) could attenuate hypoxia-induced HIF1α mRNA expression, thereby sensitizing the tumor to chemotherapy. Overall, this smart nanomedicine represents a profound targeted therapy strategy, combining "hypoxia-potentiating, hypoxia-activated, chemo-sensitization" approaches for TNBC treatment. In vivo study demonstrated significant suppression of tumor growth, highlighting the promising potential of this nanomedicine for future clinical translation.

18.
J Am Coll Radiol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969253

ABSTRACT

OBJECTIVE: Mammography and MRI screening typically occur in combination or in alternating sequence. We compared multimodality screening performance accounting for the relative timing of mammography and MRI and overlapping follow-up periods. METHODS: We identified 8,260 screening mammograms performed 2005-2017 in the Breast Cancer Surveillance Consortium, paired with screening MRIs within +/- 90 days (combined screening) or 91-270 days (alternating screening). Performance for combined screening [cancer detection rate (CDR) per 1000 examinations and sensitivity] was calculated with one-year follow-up for each modality, and with a single follow-up period treating the two tests as a single test. Alternating screening performance was calculated with one-year follow-up for each modality and also with follow-up ending at the next screen if within one year (truncated follow-up). RESULTS: For 3,810 combined screening pairs, CDR per 1000 screens was 6.8 (95%CI: 4.6-10.0) for mammography and 12.3 (95%CI: 9.3-16.4) for MRI as separate tests compared to 13.1 (95%CI: 10.0-17.3) as a single combined test. Sensitivity of each test was 48.1% (35.0%-61.5%) for mammography and 79.7% (95%CI: 67.7-88.0%) for MRI compared to 96.2% (95%CI: 85.9-99.0%) for combined screening. For 4,450 alternating screening pairs, mammography CDR per 1000 screens changed from 3.6 (95%CI: 2.2-5.9) to zero with truncated follow-up; sensitivity was incalculable (denominator=0). MRI CDR per 1000 screens changed from 12.1 (95%CI 9.3-15.8) to 11.7 (95%CI: 8.9-15.3) with truncated follow-up; sensitivity changed from 75.0% (95%CI 63.8-83.6%) to 86.7% (95%CI 75.5-93.2%). DISCUSSION: Updating auditing approaches to account for combined and alternating screening sequencing and to address outcome attribution issues arising from overlapping follow-up periods can improve the accuracy of multimodality screening performance evaluation.

19.
Semin Oncol Nurs ; : 151684, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38969573

ABSTRACT

OBJECTIVES: Aimed to determine the effect of education provided with a mobile application on the supportive care needs and quality of life of women undergoing breast-conserving surgery. METHODS: The study was conducted in 81 patients. The experimental group received mobile application and the control group received standard education. Fisher's Exact Test, Chi-Square test, Student's t Test, Mann-Whitney U test, mixed design analysis of variance and Bonferroni-Dunn test were used to analyze the data. RESULTS: While the pre-study supportive care needs scores of the women were similar in the experimental (85.37 ± 23.58) and control (83.13 ± 23.03) groups, they decreased significantly in the experimental group at the 4th and 8th-week measurements (54.34 ± 27.28; 58.78 ± 16.51) (p < .05). In the 4th and 8th week measurements, the quality of life of the experimental group (72.26 ± 14.12; 71.04 ± 8.12) increased significantly, while no significant change was found in the control group (42.50 ± 14.38; 45.63 ± 8.28). CONCLUSIONS: It was found that the supportive care needs of the decreased and their quality of life increased after the education given to women with a mobile application. IMPLICATIONS FOR NURSING PRACTICE: This study ensured that women who had a sufficiently intense and exhausting process during the cancer treatment process could comfortably receive care support and education with the mobile application at any time and place they wanted. It also revealed that nurses can provide care and education support to their patients at any time and place they want with the mobile application in their busy work tempo.

20.
Ann Surg Oncol ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969849

ABSTRACT

BACKGROUND: Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. METHODS: We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. RESULTS: The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). CONCLUSIONS: In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

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