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  1. Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, et al.
    J Pathol, 2024 Mar;262(3):271-288.
    PMID: 38230434 DOI: 10.1002/path.6238
    Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
    Matched MeSH terms: Breast Neoplasms*
  2. Kwok LS, Yian SS, Ismael LQ, Bee YTG, Harn GL, Yin KB
    Mol Biol Rep, 2024 Feb 21;51(1):317.
    PMID: 38381204 DOI: 10.1007/s11033-024-09269-z
    BACKGROUND: Our previous study investigated the levels of soluble growth factors in the conditioned media of bone marrow-derived mesenchymal stem cells (BMSCs) pre-treated with thiazolidinedione solutions. The present study aimed to investigate the complex intracellular proteins extracted from BMSCs pre-treated with pioglitazone and/or rosiglitazone using proteomics.

    METHODS: The proliferative effect of the identified protein on MCF-7 cells that interacted non-adhesively with BMSCs pre-treated with pioglitazone and/or rosiglitazone was evaluated using cell culture inserts and conditioned media. The mRNA expression of proliferation and lipid accumulation markers was also evaluated in the interacted MCF-7 cells by reverse transcription-quantitative PCR. Finally, the correlation between the identified protein and fibroblast growth factor 4 (FGF-4) protein in the conditioned media of the pre-treated BMSCs was evaluated by ELISA.

    RESULTS: The present study identified vimentin as the specific protein among the complex intracellular proteins that likely plays a role in MCF-7 cell proliferation when the breast cancer cells interacted non-adhesively with BMSCs pre-treated with a combination of pioglitazone and rosiglitazone. The inhibition of this protein promoted the proliferation of MCF-7 cells when the breast cancer cells interacted with pre-treated BMSCs. Gene expression analysis indicated that pre-treatment of BMSCs with a combination of pioglitazone and rosiglitazone decreased the mRNA expression of Ki67 and proliferating cell nuclear antigen in MCF-7 cells. The pre-treatment did not induce mRNA expression of PPARγ, which is a sign of lipid accumulation. The level of vimentin protein was also associated with the FGF-4 protein expression level in the conditioned media of the pre-treated BMSCs. Bioinformatics analysis revealed that vimentin regulated the expression of FGF-4 through its interaction with SRY-box 2 and POU class 5 homeobox 1.

    CONCLUSIONS: The present study identified a novel intracellular protein that may represent the promising target in pre-treated BMSCs to decrease the proliferation of breast cancer MCF-7 cells for human health and wellness.

    Matched MeSH terms: Breast Neoplasms*
  3. Rozilah MI, Yusoff K, Chia SL, Ismail S
    Virology, 2024 Feb;590:109957.
    PMID: 38100982 DOI: 10.1016/j.virol.2023.109957
    Newcastle disease virus (NDV) is an oncolytic virus which selectively replicates in cancer cells without harming normal cells. Autophagy is a cellular mechanism that breaks down unused cytoplasmic constituents into nutrients. In previous studies, autophagy enhanced NDV-induced oncolysis in lung cancer and glioma cells. However, the effect of autophagy inhibition on NDV-induced oncolysis in breast cancer cells remains unknown. This study aimed to examine the effect of autophagy inhibition on NDV-induced oncolysis in human breast cancer cells, MCF7. To inhibit autophagy, we knocked down the expression of the autophagy protein beclin-1 (BECN1) by short interfering RNA (siRNA). The cells were infected with the recombinant NDV strain AF2240 expressing green fluorescent protein. We found that NDV induced autophagy and knockdown of BECN1 significantly reduced the NDV-induced autophagy in MCF7 cells. Importantly, BECN1 knockdown significantly suppressed cell death by inhibiting viral replication, as observed at 24 h post infection. Overall, our data suggest that autophagy inhibition may not be a suitable strategy to enhance NDV oncolytic efficacy against breast cancer.
    Matched MeSH terms: Breast Neoplasms*
  4. Bakrim S, El Omari N, Khan EJ, Khalid A, Abdalla AN, Chook JB, et al.
    Biomed Pharmacother, 2023 Dec 31;169:115783.
    PMID: 37944439 DOI: 10.1016/j.biopha.2023.115783
    Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.
    Matched MeSH terms: Breast Neoplasms*
  5. Ahmed Shaker Hegian Z, Moh'd Abu Tahoun L, Ramli RM, Noor Azman NZ
    Radiat Prot Dosimetry, 2023 Dec 29;200(1):25-31.
    PMID: 37738470 DOI: 10.1093/rpd/ncad259
    The mean glandular dose (MGD) is a measurement used in mammography to assess the amount of radiation absorbed. By considering specific exposure radiation dose criteria, MGD ensures minimal radiation while maintaining image quality for detecting abnormalities. The relationship between MGD and compressed breast thickness (CBT) is commonly utilized in mammographic dose surveys. This study aims to estimate the MGD-CBT relationship based on patient age in Jordan through retrospective analysis. The analysis involved 3465 screening mammography images of women aged 40-80, divided into three age groups: 40-49, 50-64 and 65-80 years. Each group had a specific CBT range (16.5-156 mm). The results indicate that MGD ranges from 1.6 to 1.7 mGy across all three age groups, independent of CBT. Thus, a significant and positive correlation exists between MGD and CBT in all age groups.
    Matched MeSH terms: Breast Neoplasms*
  6. Adam SA, Kamaruddin KN, Abd Shukor N, Abdullah Suhaimi SN, Ismail F, Md Yasin M
    Am J Case Rep, 2023 Dec 04;24:e941448.
    PMID: 38048289 DOI: 10.12659/AJCR.941448
    BACKGROUND Breast squamous cell carcinoma (SCC) is a subtype of metaplastic breast carcinoma (MBC), which is a rare malignancy and accounts for 0.1% of all invasive breast carcinomas. Guidelines on definitive management and treatment of breast SCC are not well established, given its rarity and diverse immunohistochemistry (IHC) profile, and lack of clinical data. Most cases of breast SCC are triple-negative breast cancer - negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This case report outlines the clinicopathological profile of a pure breast SCC case with a rare IHC profile; HER2 and ER positive. CASE REPORT A 41-year-old woman presented with a right breast mass that had been growing for 2 months. Biopsy confirmed breast SCC, a rare malignancy with IHC profile as follows: HER2 overexpression, ER positive, and PR negative. She underwent neoadjuvant chemotherapy for 3 months followed by right mastectomy with axillary clearance, adjuvant radiotherapy, and oral tamoxifen therapy. Unfortunately, she did not receive anti-HER2 therapy. She developed early locoregional recurrence at 2 months postoperatively, which was treated with excision of the right chest wall and transverse rectus abdominis musculocutaneous (TRAM) flap. She developed liver and lung metastasis and succumbed to her disease at 15 months post-diagnosis. CONCLUSIONS Breast SCC is a rare and aggressive tumor with heterogeneous clinicopathological features. Available guidelines do not outline the definitive treatment for breast SCC, given its rarity and heterogenous IHC profile, leading to a general lack of clinical data. Hence, due to the challenges in managing this rare condition, treatment modalities need to be individualized.
    Matched MeSH terms: Triple Negative Breast Neoplasms*
  7. Bharathi D, Ranjithkumar R, Nandagopal JGT, Djearamane S, Lee J, Wong LS
    Environ Res, 2023 Dec 01;238(Pt 1):117109.
    PMID: 37696324 DOI: 10.1016/j.envres.2023.117109
    The synthesis of polymer-encapsulated metal nanoparticles is a growing field of area due to their long-term uses in the development of new technologies. The present study describes the synthesis of chitosan/silver nanocomposite using kaempferol for anticancer and bactericidal activity. The formation of Kf-CS/Ag nanocomposite was confirmed by the development of a brown color and UV-absorbance around 438 nm. The IR study was utilized to determine the existence of Kf and CS in the synthesized nanocomposite. TEM analysis demonstrated that the synthesized nanocomposite have a predominantly uniform spherical shape and size ranges 7-10 nm. EDX spectrum showed the existence of Ag, C, and N elements in the nanocomposite material. Further, Kf-CS/Ag nanocomposite exhibited potential in vitro inhibitory property against triple-negative breast cancer (TNBC) cells and their IC50 values was found to be 53 μg/mL. Moreover, fluorescent assays such as DAPI and AO/EtBr confirmed the apoptosis induction ability of Kf-CS/Ag nanocomposite in MDA-MB-231 cells. The synthesized Kf-CS/Ag nanocomposite showed significant and dose-depended antibacterial property against S. aureus and P. aeruginosa. Thus, the obtained findings demonstrated that the synthesized nanocomposite can be potentially used to improve human health as biocidal nanocomposite in biomedical sectors.
    Matched MeSH terms: Triple Negative Breast Neoplasms*
  8. Mohd Omar R, Ismail IA, Md Yasin M, Ahmad Affandi K, Hasbullah HH, Mohamad Ali ND
    Am J Case Rep, 2023 Aug 23;24:e940594.
    PMID: 37608536 DOI: 10.12659/AJCR.940594
    BACKGROUND Carcinoma of unknown primary (CUP) is a diverse category of malignancies diagnosed in patients who have metastatic disease but without an identifiable primary tumor at initial presentation. CASE REPORT We report a case of CUP which was later diagnosed to be metastatic adenocarcinoma of the breast in a 62-year-old woman. The patient initially presented to a primary care clinic with an incidental finding of a small hard mass in the middle of the sternum, with no other clinical findings in the breast or axillary lymph nodes. Chest X-ray, ultrasound, and CT scan of the sternum suggested a benign sternal lesion, and a mammogram was normal. Due to the persistence of the mass, a biopsy was performed. The histopathological findings revealed a metastatic adenocarcinoma, most likely from breast origin, with positive estrogen receptor (ER) and mammaglobin on immunohistochemistry studies. The patient subsequently underwent PET scan, repeat mammogram, and MRI of the breast. Following high uptake in the rectum on PET, a colonoscopy was performed, revealing a suspicious rectal mass. The mass was surgically excised, and the final histopathological examination concluded the mass was a second primary adenocarcinoma of the rectum. Genetic analyses for BRCA1 and BRCA2 were negative. CONCLUSIONS This is a rare case of an isolated bone-like lesion on the sternum due to metastatic adenocarcinoma of the breast in a patient with no prior history of breast cancer and lacking any clinical or radiological evidence of breast or axillary lymph node lesions on presentation. The patient was also subsequently diagnosed with 2 primary carcinomas. Thorough clinical examination, extensive radiological investigations, laboratory investigations, histopathological examination, and a multidisciplinary approach are essential in managing CUP.
    Matched MeSH terms: Breast Neoplasms*
  9. Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.
    J Pathol, 2023 Aug;260(5):498-513.
    PMID: 37608772 DOI: 10.1002/path.6155
    The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
    Matched MeSH terms: Triple Negative Breast Neoplasms*
  10. Chung FF, Maldonado SG, Nemc A, Bouaoun L, Cahais V, Cuenin C, et al.
    Clin Epigenetics, 2023 Jun 12;15(1):102.
    PMID: 37309009 DOI: 10.1186/s13148-023-01509-6
    BACKGROUND: Epigenetic alterations are a near-universal feature of human malignancy and have been detected in malignant cells as well as in easily accessible specimens such as blood and urine. These findings offer promising applications in cancer detection, subtyping, and treatment monitoring. However, much of the current evidence is based on findings in retrospective studies and may reflect epigenetic patterns that have already been influenced by the onset of the disease.

    METHODS: Studying breast cancer, we established genome-scale DNA methylation profiles of prospectively collected buffy coat samples (n = 702) from a case-control study nested within the EPIC-Heidelberg cohort using reduced representation bisulphite sequencing (RRBS).

    RESULTS: We observed cancer-specific DNA methylation events in buffy coat samples. Increased DNA methylation in genomic regions associated with SURF6 and REXO1/CTB31O20.3 was linked to the length of time to diagnosis in the prospectively collected buffy coat DNA from individuals who subsequently developed breast cancer. Using machine learning methods, we piloted a DNA methylation-based classifier that predicted case-control status in a held-out validation set with 76.5% accuracy, in some cases up to 15 years before clinical diagnosis of the disease.

    CONCLUSIONS: Taken together, our findings suggest a model of gradual accumulation of cancer-associated DNA methylation patterns in peripheral blood, which may be detected long before clinical manifestation of cancer. Such changes may provide useful markers for risk stratification and, ultimately, personalized cancer prevention.

    Matched MeSH terms: Breast Neoplasms*
  11. Pivot X, Cortés J, Lüftner D, Lyman GH, Curigliano G, Bondarenko IM, et al.
    JAMA Netw Open, 2023 Apr 03;6(4):e235822.
    PMID: 37022687 DOI: 10.1001/jamanetworkopen.2023.5822
    IMPORTANCE: Trastuzumab has been the standard of care for the treatment of patients with ERBB2-positive breast cancer; however, cardiac events have been reported. This long-term follow-up study provides clinical evidence supporting the similarity of a trastuzumab biosimilar (SB3) to reference trastuzumab (TRZ).

    OBJECTIVE: To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up.

    DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment.

    INTERVENTIONS: In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years.

    MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS).

    RESULTS: A total of 538 female patients were included (median age, 51 years [range, 22-65 years]). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient [0.4%]; TRZ, 2 [0.7%]). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients [SB3, n = 267; TRZ, n = 271]). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio [HR], 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group.

    CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer.

    TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02771795.

    Matched MeSH terms: Breast Neoplasms*
  12. Rajaram N, Jaganathan M, Muniandy K, Rajoo Y, Zainal H, Rahim N, et al.
    BMC Health Serv Res, 2023 Mar 01;23(1):206.
    PMID: 36859265 DOI: 10.1186/s12913-023-09046-x
    BACKGROUND: Improving help-seeking behaviour is a key component of down-staging breast cancer and improving survival, but the specific challenges faced by low-income women in an Asian setting remain poorly characterized. Here, we determined the extent of help-seeking delay among Malaysian breast cancer patients who presented at late stages and explored sub-groups of women who may face specific barriers.

    METHODS: Time to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks.

    RESULTS: The average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p breast health or breast cancer symptoms (36.3%), regardless of help-seeking behaviour (p = 0.931). Unexpectedly, women with no delay (9 days average) and great delay (259 days average) were more similar to each other than to women with mild delays (58 days average), but, women who experienced great delay reported poor motivation due to fear and embarrassment (p = 0.066) and a lack of social support (p = 0.374) to seek help.

    CONCLUSIONS: Down-staging of breast cancer in Malaysia will require a multi-pronged approach aimed at modifying culturally specific social and emotional barriers, eliminating misinformation, and instilling motivation to seek help for breast health for the women most vulnerable to help-seeking delays.

    Matched MeSH terms: Breast Neoplasms*
  13. Sham NFR, Hasani NAH, Hasan N, Karim MKA, Fuad SBSA, Hasbullah HH, et al.
    Sci Rep, 2023 Feb 22;13(1):3108.
    PMID: 36813833 DOI: 10.1038/s41598-023-29925-x
    Cancer recurrence is often associated with the acquisition of radioresistance by cancer tissues due to failure in radiotherapy. The underlying mechanism leading to the development of acquired radioresistance in the EMT6 mouse mammary carcinoma cell line and the potential pathway involved was investigated by comparing differential gene expressions between parental and acquired radioresistance cells. EMT6 cell line was exposed to 2 Gy/per cycle of gamma-ray and the survival fraction between EMT6-treated and parental cells was compared. EMT6RR_MJI (acquired radioresistance) cells was developed after 8 cycles of fractionated irradiation. The development of EMT6RR_MJI cells was confirmed with further irradiation at different doses of gamma-ray, and both the survival fraction and migration rates were measured. Higher survival fraction and migration rates were obtained in EMT6RR_MJI cells after exposure to 4 Gy and 8 Gy gamma-ray irradiations compared to their parental cells. Gene expression between EMT6RR_MJI and parental cells was compared, and 16 genes identified to possess more than tenfold changes were selected and validated using RT-PCR. Out of these genes, 5 were significantly up-regulated i.e., IL-6, PDL-1, AXL, GAS6 and APCDD1. Based on pathway analysis software, the development of acquired radioresistance in EMT6RR_MJI was hypothesized through JAK/STAT/PI3K pathway. Presently, CTLA-4 and PD-1 were determined to be associated with JAK/STAT/PI3K pathway, where both their expressions were significantly increased in EMT6RR_MJI compared to parental cells in the 1st, 4th and 8th cycle of radiation. As a conclusion, the current findings provided a mechanistic platform for the development of acquired radioresistance in EMT6RR_MJI through overexpression of CTLA-4 and PD-1, and novel knowledge on therapeutic targets for recurrent radioresistant cancers.
    Matched MeSH terms: Breast Neoplasms*
  14. Nik Ab Kadir MN, Mohd Hairon S, Yaacob NM, Yusof SN, Musa KI, Yahya MM, et al.
    PMID: 36833678 DOI: 10.3390/ijerph20042985
    Women with breast cancer are keen to know their predicted survival. We developed a new prognostic model for women with breast cancer in Malaysia. Using the model, this study aimed to design the user interface and develop the contents of a web-based prognostic tool for the care provider to convey survival estimates. We employed an iterative website development process which includes: (1) an initial development stage informed by reviewing existing tools and deliberation among breast surgeons and epidemiologists, (2) content validation and feedback by medical specialists, and (3) face validation and end-user feedback among medical officers. Several iterative prototypes were produced and improved based on the feedback. The experts (n = 8) highly agreed on the website content and predictors for survival with content validity indices ≥ 0.88. Users (n = 20) scored face validity indices of more than 0.90. They expressed favourable responses. The tool, named Malaysian Breast cancer Survival prognostic Tool (myBeST), is accessible online. The tool estimates an individualised five-year survival prediction probability. Accompanying contents were included to explain the tool's aim, target user, and development process. The tool could act as an additional tool to provide evidence-based and personalised breast cancer outcomes.
    Matched MeSH terms: Breast Neoplasms*
  15. Rahman H, Naik Bukht TF, Ahmad R, Almadhor A, Javed AR
    Comput Intell Neurosci, 2023;2023:7717712.
    PMID: 36909966 DOI: 10.1155/2023/7717712
    Medical image analysis places a significant focus on breast cancer, which poses a significant threat to women's health and contributes to many fatalities. An early and precise diagnosis of breast cancer through digital mammograms can significantly improve the accuracy of disease detection. Computer-aided diagnosis (CAD) systems must analyze the medical imagery and perform detection, segmentation, and classification processes to assist radiologists with accurately detecting breast lesions. However, early-stage mammography cancer detection is certainly difficult. The deep convolutional neural network has demonstrated exceptional results and is considered a highly effective tool in the field. This study proposes a computational framework for diagnosing breast cancer using a ResNet-50 convolutional neural network to classify mammogram images. To train and classify the INbreast dataset into benign or malignant categories, the framework utilizes transfer learning from the pretrained ResNet-50 CNN on ImageNet. The results revealed that the proposed framework achieved an outstanding classification accuracy of 93%, surpassing other models trained on the same dataset. This novel approach facilitates early diagnosis and classification of malignant and benign breast cancer, potentially saving lives and resources. These outcomes highlight that deep convolutional neural network algorithms can be trained to achieve highly accurate results in various mammograms, along with the capacity to enhance medical tools by reducing the error rate in screening mammograms.
    Matched MeSH terms: Breast Neoplasms*
  16. Rohilla S, Singh M, Priya S, Almalki WH, Haniffa SM, Subramaniyan V, et al.
    PMID: 36734949 DOI: 10.1615/JEnvironPatholToxicolOncol.2022042088
    Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.
    Matched MeSH terms: Breast Neoplasms*
  17. Ng WH, Abu Zaid Z, Mohd Yusof BN, Amin Nordin S, Lim PY
    Ann Med, 2023;55(2):2303399.
    PMID: 38242100 DOI: 10.1080/07853890.2024.2303399
    BACKGROUND: Obesity, particularly excessive body fat, is an established risk factor and substantial prognostic determinant in breast cancer. Recent studies suggested that diet-related inflammation plays a key role in obesity. This study aimed to determine the association between energy-adjusted dietary inflammatory index (E-DII) and body composition, particularly body fat percentage, among patients with newly diagnosed breast cancer.

    MATERIALS AND METHODS: This cross-sectional study was conducted on 124 breast cancer outpatients within the first year of diagnosis and yet to commence oncological treatment. Body composition parameters [body weight, body mass index (BMI), body fat percentage, fat mass over fat-free mass ratio (FM/FFM), muscle mass, and visceral fat] were obtained using a bioelectrical impedance analyzer. Body fat percentage was categorized into two groups which were normal (<35%) and high (≥35%). The E-DII was calculated from the validated 165-items Food Frequency Questionnaire (FFQ) and categorized into three groups or tertiles. Multiple logistic regression analysis was used to determine the association between the E-DII and body fat percentage.

    RESULTS: Mean body weight, body fat percentage, FM/FFM, and visceral fat increased as E-DII increased from the lowest tertile (T1) to the most pro-inflammatory tertile (T3) (p for trend <0.05). E-DII was positively associated with body fat percentage (OR 2.952; 95% CI 1.154-7.556; p = 0.024) and remained significant after adjustment for cancer stage, age, physical activity, ethnicity, smoking history, and presence of comorbidities. Compared to T1, participants in T3 had a significantly lower consumption of fiber, vitamin A, beta-carotene, vitamin C, iron, thiamine, riboflavin, niacin, vitamin B6, folic acid, zinc, magnesium, and selenium, but a higher intake of total fat, saturated fat, and monounsaturated fatty acids.

    CONCLUSIONS: A higher E-DII was associated with increased body fat percentage, suggesting the potential of advocating anti-inflammatory diet to combat obesity among newly diagnosed breast cancer patients.

    Matched MeSH terms: Breast Neoplasms*
  18. Nik Ab Kadir MN, Yaacob NM, Yusof SN, Ab Hadi IS, Musa KI, Mohd Isa SA, et al.
    Int J Environ Res Public Health, 2022 Nov 20;19(22).
    PMID: 36430052 DOI: 10.3390/ijerph192215335
    Prediction of survival probabilities based on models developed by other countries has shown inconsistent findings among Malaysian patients. This study aimed to develop predictive models for survival among women with breast cancer in Malaysia. A retrospective cohort study was conducted involving patients who were diagnosed between 2012 and 2016 in seven breast cancer centres, where their survival status was followed until 31 December 2021. A total of 13 predictors were selected to model five-year survival probabilities by applying Cox proportional hazards (PH), artificial neural networks (ANN), and decision tree (DT) classification analysis. The random-split dataset strategy was used to develop and measure the models' performance. Among 1006 patients, the majority were Malay, with ductal carcinoma, hormone-sensitive, HER2-negative, at T2-, N1-stage, without metastasis, received surgery and chemotherapy. The estimated five-year survival rate was 60.5% (95% CI: 57.6, 63.6). For Cox PH, the c-index was 0.82 for model derivation and 0.81 for validation. The model was well-calibrated. The Cox PH model outperformed the DT and ANN models in most performance indices, with the Cox PH model having the highest accuracy of 0.841. The accuracies of the DT and ANN models were 0.811 and 0.821, respectively. The Cox PH model is more useful for survival prediction in this study's setting.
    Matched MeSH terms: Breast Neoplasms*
  19. Sharmni Vishnu K, Win TT, Aye SN, Basavaraj AK
    BMC Cancer, 2022 Nov 05;22(1):1139.
    PMID: 36335316 DOI: 10.1186/s12885-022-10225-y
    BACKGROUND: Triple negative breast cancer (TNBC) is clinically aggressive breast cancer with a poor prognosis. Approximately 20% of TNBC has been found to express programmed death ligand 1 (PD-L1), making it a potential therapeutic target. As a PD-L1 inhibitor, atezolizumab is a recently approved immunotherapeutic drug for TNBC, this meta-analysis (MA) was aimed to review the randomized controlled trial studies (RCTs) of combined atezolizumab and nab-paclitaxel in the treatment of TNBC and synthesize the evidence-based results on its effectiveness and safety.

    METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).

    RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).

    CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.

    TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).

    Matched MeSH terms: Triple Negative Breast Neoplasms*
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