Search results for: breast cancer/therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3780

Search results for: breast cancer/therapy

3540 TP53 Mutations in Molecular Subtypes of Breast Cancer in Young Pakistani Patients

Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

Abstract:

Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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3539 The Colorectal Cancer in Patients of Eastern Algeria

Authors: S. Tebibel, C. Mechati, S. Messaoudi

Abstract:

Algeria is currently experiencing the same rate of cancer progression as that registered these last years in the western countries. Colorectal cancer, constituting increasingly a major public health problem, is the most common form of cancer after breast and Neck-womb cancer at the woman and prostate cancer at the man. Our work is based on a retrospective study to determine the cases of colorectal cancer through eastern Algeria. Our goal is to carry out an epidemiological, histological and immune- histochemical study to investigate different techniques for the diagnosis of colorectal cancer and their interests and specific in detecting the disease. The study includes 110 patients (aged between 20 to 87 years) with colorectal cancer where the inclusions and exclusions criteria were established. In our study, colorectal cancer, expresses a male predominance, with a sex ratio of 1, 99 and the most affected age group is between 50 and 59 years. We noted that the colon cancer rate is higher than rectal cancer rate, whose frequencies are respectively 60,91 % and 39,09 %. In the series of colon cancer, the ADK lieberkunien is histological the most represented type, or 85,07 % of all cases. In contrast, the proportion of ADK mucinous (colloid mucous) is only 1,49% only. Well-differentiated ADKS, are very significant in our series, they represent 83,58 % of cases. Adenocarcinoma moderately and poorly differentiated, whose proportions are respectively 2,99 % and 0.05 %. For histological varieties of rectal ADK, we see in our workforce that ADK lieberkunien represent the most common histological form, or 76,74%, while the mucosal colloid is 13,95 %. Research of the mutation on the gene encoding K-ras, a major step in the targeted therapy of colorectal cancers, is underway in our study. Colorectal cancer is the subject of much promising research concern: the evaluation of new therapies (antiangiogenic monoclonal antibodies), the search for predictors of sensitivity to chemotherapy and new prognostic markers using techniques of molecular biology and proteomics.

Keywords: adenocarcinoma, age, colorectal cancer, epidemiology, histological section, sex

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3538 Comparison of Stereotactic Body Radiation Therapy Virtual Treatment Plans Obtained With Different Collimators in the Cyberknife System in Partial Breast Irradiation: A Retrospective Study

Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

Abstract:

It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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3537 Dietary Patterns and Adherence to the Mediterranean Diet among Breast Cancer Female Patients in Lebanon: A Cross-Sectional Study

Authors: Yasmine Aridi, Lara Nasreddine, Maya Khalil, Arafat Tfayli, Anas Mugharbel, Farah Naja

Abstract:

Breast cancer is the most commonly diagnosed cancer site among women worldwide and the second most common cause of cancer mortality. Breast cancer rates differ vastly between geographical areas, countries, and within the same country. In Lebanon, the proportion of breast cancer to all other sites of tumor is 38.2%; these rates are still lower than those observed worldwide, but remain the highest among Arab countries. Studies and evidence based reviews show a strong association between breast cancer development and prognosis and dietary habits, specifically the Mediterranean diet (MD). As such, the aim of this study is to examine dietary patterns and adherence to the MD among a sample of 182 breast cancer female patients in Beirut, Lebanon. Subjects were recruited from two major hospitals; a private medical center and a public hospital. All subjects were administered two questionnaires: socio- demographics and Mediterranean diet adherence. Five Mediterranean scores were calculated: MS, MSDPS, PMDI, PREDIMED and DDS. The mean age of the participants was 53.78 years. The overall adherence to the Mediterranean diet (MD) was low since the sample means of 3 out of the 5 calculated scores were less than the scores’ medians. Given that 4 out of the 5 Mediterranean scores significantly varied between the recruitment sites, women in the private medical center were found to adhere more to the MD. Our results also show that the majority of the sample population’s intakes are exceeding the recommendations for total and saturated fat, while meeting the requirements for fiber, EPA, DHA and Linolenic Acid. Participants in the private medical center were consuming significantly more calories, carbohydrates, fiber, sugar, Lycopene, Calcium, Iron and Folate and less fat. After conducting multivariate linear regression analyses, the following significant results were observed: positive associations between MD (CPMDI, PREDIMED) and monthly income & current state of health, while negative associations between MD (MSDPS, PREDIMED) and age & employment status. Our findings indicated a low overall adherence to the MD and identified factors associated with it; which suggests a need to address dietary habits among BC patients in Lebanon, specifically encouraging them to adhere to their traditional Mediterranean diet.

Keywords: Adherence, Breast cancer, Dietary patterns, Mediterranean diet, Nutrition

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3536 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

Abstract:

MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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3535 The Analysis of Personalized Low-Dose Computed Tomography Protocol Based on Cumulative Effective Radiation Dose and Cumulative Organ Dose for Patients with Breast Cancer with Regular Chest Computed Tomography Follow up

Authors: Okhee Woo

Abstract:

Purpose: The aim of this study is to evaluate 2-year cumulative effective radiation dose and cumulative organ dose on regular follow-up computed tomography (CT) scans in patients with breast cancer and to establish personalized low-dose CT protocol. Methods and Materials: A retrospective study was performed on the patients with breast cancer who were diagnosed and managed consistently on the basis of routine breast cancer follow-up protocol between 2012-01 and 2016-06. Based on ICRP (International Commission on Radiological Protection) 103, the cumulative effective radiation doses of each patient for 2-year follow-up were analyzed using the commercial radiation management software (Radimetrics, Bayer healthcare). The personalized effective doses on each organ were analyzed in detail by the software-providing Monte Carlo simulation. Results: A total of 3822 CT scans on 490 patients was evaluated (age: 52.32±10.69). The mean scan number for each patient was 7.8±4.54. Each patient was exposed 95.54±63.24 mSv of radiation for 2 years. The cumulative CT radiation dose was significantly higher in patients with lymph node metastasis (p = 0.00). The HER-2 positive patients were more exposed to radiation compared to estrogen or progesterone receptor positive patient (p = 0.00). There was no difference in the cumulative effective radiation dose with different age groups. Conclusion: To acknowledge how much radiation exposed to a patient is a starting point of management of radiation exposure for patients with long-term CT follow-up. The precise and personalized protocol, as well as iterative reconstruction, may reduce hazard from unnecessary radiation exposure.

Keywords: computed tomography, breast cancer, effective radiation dose, cumulative organ dose

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3534 Comparison of the Indocyanine Green Dye Method versus the Combined Method of Indigo Carmine Blue Dye with Indocyanine Green Fluorescence Imaging for Sentinel Lymph Node Biopsy in Breast Conservative Therapy for Early Breast Cancer

Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

Abstract:

Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

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3533 Mammographic Multi-View Cancer Identification Using Siamese Neural Networks

Authors: Alisher Ibragimov, Sofya Senotrusova, Aleksandra Beliaeva, Egor Ushakov, Yuri Markin

Abstract:

Mammography plays a critical role in screening for breast cancer in women, and artificial intelligence has enabled the automatic detection of diseases in medical images. Many of the current techniques used for mammogram analysis focus on a single view (mediolateral or craniocaudal view), while in clinical practice, radiologists consider multiple views of mammograms from both breasts to make a correct decision. Consequently, computer-aided diagnosis (CAD) systems could benefit from incorporating information gathered from multiple views. In this study, the introduce a method based on a Siamese neural network (SNN) model that simultaneously analyzes mammographic images from tri-view: bilateral and ipsilateral. In this way, when a decision is made on a single image of one breast, attention is also paid to two other images – a view of the same breast in a different projection and an image of the other breast as well. Consequently, the algorithm closely mimics the radiologist's practice of paying attention to the entire examination of a patient rather than to a single image. Additionally, to the best of our knowledge, this research represents the first experiments conducted using the recently released Vietnamese dataset of digital mammography (VinDr-Mammo). On an independent test set of images from this dataset, the best model achieved an AUC of 0.87 per image. Therefore, this suggests that there is a valuable automated second opinion in the interpretation of mammograms and breast cancer diagnosis, which in the future may help to alleviate the burden on radiologists and serve as an additional layer of verification.

Keywords: breast cancer, computer-aided diagnosis, deep learning, multi-view mammogram, siamese neural network

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3532 Synthesis of Size-Tunable and Stable Iron Nanoparticles for Cancer Treatment

Authors: Ambika Selvaraj

Abstract:

Magnetic iron oxide nanoparticles (IO) of < 20nm (superparamagnetic) become promising tool in cancer therapy, and integrated nanodevices for cancer detection and screening. The obstacles include particle heterogeneity and cost. It can be overcome by developing monodispersed nanoparticles in economical approach. We have successfully synthesized < 7 nm IO by low temperature controlled technique, in which Fe0 is sandwiched between stabilizer and Fe2+. Size analysis showed the excellent size control from 31 nm at 33°C to 6.8 nm at 10°C. Resultant monodispersed IO were found to be stable for > 50 reuses, proved its applicability in biomedical applications.

Keywords: low temperature synthesis, hybrid iron nanoparticles, cancer therapy, biomedical applications

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3531 Triggering Apoptosis to Uproot Breast Cancer: HPLC-MS/MS Profiling, in-vitro and in-silico Fascinating Results of Polyphenolics in Pomegranate Rind Extract

Authors: Alaa M. Badr Eldin, Mayar M. Shahen, Mohammed S. Sedeek, Marwa I. Ezzat, Sawsan M. ElSonbaty, Muhammed A. Saad, Manal S. Afifi, Omar M. Sabry

Abstract:

Using HPLC-MS/MS technique, 133 polyphenolic compounds were identified in the methanol extract of pomegranate rind (Punica granatum L.). In-vitro cytotoxic activity against breast cancer cell line MCF-7 was investigated, with an IC50 of 54 ug/ml. In-silico molecular docking using ellagic acid, gallagic acid, and Punicalagin as model compounds identified in pomegranate rind extract confirmed the intriguing anti-estrogenic action of the key polyphenolic components in pomegranate rind extract. Surprisingly, taxol showed low activity compared to pomegranate compounds as ERα antagonist and ERβ agonist. Pomegranate rind extract enhanced apoptosis of breast cancer cells through upregulation of the caspase-3 expression and downregulation of NF-κB transcription factor.

Keywords: HPLC-MS/MS, pomegranate rind, cytotoxicity, MCF-7, ER, caspase-3, NF-kB

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3530 Exploring Cultural Safety for Individuals from Culturally and Linguistically Diverse Backgrounds Participating in Breast Screening

Authors: Philippa Sambevski

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Breast cancer is the most common cancer diagnosed in Australian women. The incidence of breast cancer for Aboriginal and Torres Strait Islander (ATSI) women is lower than for non-indigenous women. However, the mortality rate for ATSI women is higher. The participation rate of ATSI women in BreastScreen Australia is below the general population. In this thematic literature review, the author collates viable strategies to increase breast screening rates among culturally and linguistically diverse individuals and provide culturally competent care. Barriers to accessing BreastScreen for ATSI women include language or communication limits, isolation, and a lack of culturally sensitive information. Culturally competent strategies require healthcare workers with an appropriate cultural and social background, clear messages, and the embedding of cultural respect within healthcare organisations. Cultural safety is determined by partnering with local indigenous groups, recognising the consumer experience, and allowing people to raise their concerns. The corresponding academic poster identifies strategies for healthcare workers to provide culturally competent care in a BreastScreen setting.

Keywords: breast screen, closing the gap, Australia, cultural safety, Aboriginal and Torres Strait Islander

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3529 The Use of Medical Biotechnology to Treat Genetic Disease

Authors: Rachel Matar, Maxime Merheb

Abstract:

Chemical drugs have been used for many centuries as the only way to cure diseases until the novel gene therapy has been created in 1960. Gene therapy is based on the insertion, correction, or inactivation of genes to treat people with genetic illness (1). Gene therapy has made wonders in Parkison’s, Alzheimer and multiple sclerosis. In addition to great promises in the healing of deadly diseases like many types of cancer and autoimmune diseases (2). This method implies the use of recombinant DNA technology with the help of different viral and non-viral vectors (3). It is nowadays used in somatic cells as well as embryos and gametes. Beside all the benefits of gene therapy, this technique is deemed by some opponents as an ethically unacceptable treatment as it implies playing with the genes of living organisms.

Keywords: gene therapy, genetic disease, cancer, multiple sclerosis

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3528 Cytotoxic Activity of Acetone and Ethanol Overripe Tempe Extracts against MCF-7 Breast Cancer Cells and Their Antioxidant Property

Authors: Dian Muzdalifah, Anastasia F. Devi, Zatil A. Athaillah, Linar Z. Udin

Abstract:

Tempe is a functional food prepared from soybeans through Rhizopus spp fermentation. It is well known as functional food, originated from Indonesia. Most studies on tempe functionalities refer to ripe (48 h fermentation) tempe and only limited studies discuss overripe tempe while longer fermentation time possibly increased tempe health benefit. Hence, the present study was performed to investigate the cytotoxic activity againts MCF-7 breast cancer cells and antioxidant property of tempe prepared from 0–156 h of fermentation. Tempe samples were dried and extracted with acetone and ethanol, respectively. Their extracts were used for subsequent analysis. The cytotoxic activity was assessed on MCF 7 breast cancer cells using Alamar Blue method. The antioxidant activity was determined by DPPH free radical scavenging assay. The results indicated that acetone extracts of 108 h tempe had a potent cytotoxic activity against MCF-7 breast cancer cells (IC50 = 2.54 ± 0,30 μg/mL). Ethanol extracts of 108 h tempe also showed the potency, but at slightly higher IC50 (5.20 ± 1.01 μg/mL). Both acetone and ethanol extracts of 108 and 120 h tempe showed high antioxidant activity expressed as percent inhibition with no significant difference. However, acetone extracts of 120 h tempe (81.31 ± 3.70 %) had better ability to inhibit oxidation reaction than that of ethanol extracts (75.77 ± 6.00 %). It can be concluded that the cytotoxic activity of tempe from 0–156 h of fermentation is positively correlated to their corresponding antioxidant property. Longer fermentation time, up to 108 h, increased the ability of tempe to inhibit the growth of MCF-7 breast cancer cells and oxidative reaction. But extended fermentation time, up to 156 h, tends to decrease its ability. Further studies are encouraged to identify the active components contained in each extract.

Keywords: antioxidant property, cytotoxic activity, extracts, overripe tempeh

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3527 Mathematical Model of Cancer Growth under the Influence of Radiation Therapy

Authors: Beata Jackowska-Zduniak

Abstract:

We formulate and analyze a mathematical model describing dynamics of cancer growth under the influence of radiation therapy. The effect of this type of therapy is considered as an additional equation of discussed model. Numerical simulations show that delay, which is added to ordinary differential equations and represent time needed for transformation from one type of cells to the other one, affects the behavior of the system. The validation and verification of proposed model is based on medical data. Analytical results are illustrated by numerical examples of the model dynamics. The model is able to reconstruct dynamics of treatment of cancer and may be used to determine the most effective treatment regimen based on the study of the behavior of individual treatment protocols.

Keywords: mathematical modeling, numerical simulation, ordinary differential equations, radiation therapy

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3526 Classification of Potential Biomarkers in Breast Cancer Using Artificial Intelligence Algorithms and Anthropometric Datasets

Authors: Aref Aasi, Sahar Ebrahimi Bajgani, Erfan Aasi

Abstract:

Breast cancer (BC) continues to be the most frequent cancer in females and causes the highest number of cancer-related deaths in women worldwide. Inspired by recent advances in studying the relationship between different patient attributes and features and the disease, in this paper, we have tried to investigate the different classification methods for better diagnosis of BC in the early stages. In this regard, datasets from the University Hospital Centre of Coimbra were chosen, and different machine learning (ML)-based and neural network (NN) classifiers have been studied. For this purpose, we have selected favorable features among the nine provided attributes from the clinical dataset by using a random forest algorithm. This dataset consists of both healthy controls and BC patients, and it was noted that glucose, BMI, resistin, and age have the most importance, respectively. Moreover, we have analyzed these features with various ML-based classifier methods, including Decision Tree (DT), K-Nearest Neighbors (KNN), eXtreme Gradient Boosting (XGBoost), Logistic Regression (LR), Naive Bayes (NB), and Support Vector Machine (SVM) along with NN-based Multi-Layer Perceptron (MLP) classifier. The results revealed that among different techniques, the SVM and MLP classifiers have the most accuracy, with amounts of 96% and 92%, respectively. These results divulged that the adopted procedure could be used effectively for the classification of cancer cells, and also it encourages further experimental investigations with more collected data for other types of cancers.

Keywords: breast cancer, diagnosis, machine learning, biomarker classification, neural network

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3525 Therapeutical Role of Copper Oxide Nanoparticles (CuO NPs) for Breast Cancer Therapy

Authors: Dipranjan Laha, Parimal Karmakar

Abstract:

Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30 nm) induce autophagy in human breast cancer cell line, MCF7 in a time and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and western blotting of autophagy marker proteins LC3B, beclin1, and ATG5. Further, inhibition of autophagy by 3-Methyladenine (3-MA) decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, dephosphorylation of Bad and increased cleavage product of caspase3. siRNA-mediated inhibition of autophagy-related gene beclin1 also demonstrated similar results. Finally, induction of apoptosis by 3-MA in CuO NPs treated cells were observed by TEM. This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NPs mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. Acknowledgments: The authors would like to acknowledge for financial support for this research work to the Department of Biotechnology (No. BT/PR14661/NNT/28/494/2010), Government of India.

Keywords: nanoparticle, autophagy, apoptosis, siRNA-mediated inhibition

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3524 Molecular Docking Analysis of Flavonoids Reveal Potential of Eriodictyol for Breast Cancer Treatment

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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3523 Understanding Jordanian Women's Values and Beliefs Related to Prevention and Early Detection of Breast Cancer

Authors: Khlood F. Salman, Richard Zoucha, Hani Nawafleh

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Introduction: Jordan ranks the fourth highest breast cancer prevalence after Lebanon, Bahrain, and Kuwait. Considerable evidence showed that cultural, ethnic, and economic differences influence a woman’s practice to early detection and prevention of breast cancer. Objectives: To understand women’s health beliefs and values in relation to early detection of breast cancer; and to explore the impact of these beliefs on their decisions regarding reluctance or acceptance of early detection measures such as mammogram screening. Design: A qualitative focused ethnography was used to collect data for this study. Settings: The study was conducted in the second largest city surrounded by a large rural area in Ma’an- Jordan. Participants: A total of twenty seven women, with no history of breast cancer, between the ages of 18 and older, who had prior health experience with health providers, and were willing to share elements of personal health beliefs related to breast health within the larger cultural context. The participants were recruited using the snowball method and words of mouth. Data collection and analysis: A short questionnaire was designed to collect data related to socio demographic status (SDQ) from all participants. A Semi-structured interviews guide was used to elicit data through interviews with the informants. Nvivo10 a data manager was utilized to assist with data analysis. Leininger’s four phases of qualitative data analysis was used as a guide for the data analysis. The phases used to analyze the data included: 1) Collecting and documenting raw data, 2) Identifying of descriptors and categories according to the domains of inquiry and research questions. Emic and etic data is coded for similarities and differences, 3) Identifying patterns and contextual analysis, discover saturation of ideas and recurrent patterns, and 4) Identifying themes and theoretical formulations and recommendations. Findings: Three major themes were emerged within the cultural and religious context; 1. Fear, denial, embarrassment and lack of knowledge were common perceptions of Ma’anis’ women regarding breast health and screening mammography, 2. Health care professionals in Jordan were not quick to offer information and education about breast cancer and screening, and 3. Willingness to learn about breast health and cancer prevention. Conclusion: The study indicated the disparities between the infrastructure and resourcing in rural and urban areas of Jordan, knowledge deficit related to breast cancer, and lack of education about breast health may impact women’s decision to go for a mammogram screening. Cultural beliefs, fear, embarrassments as well as providers lack of focus on breast health were significant contributors against practicing breast health. Health providers and policy makers should provide resources for the establishment health education programs regarding breast cancer early detection and mammography screening. Nurses should play a major role in delivering health education about breast health in general and breast cancer in particular. A culturally appropriate health awareness messages can be used in creating educational programs which can be employed at the national levels.

Keywords: breast health, beliefs, cultural context, ethnography, mammogram screening

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3522 Trajectories of Depression Anxiety and Stress among Breast Cancer Patients: Assessment at First Year of Diagnosis

Authors: Jyoti Srivastava, Sandhya S. Kaushik, Mallika Tewari, Hari S. Shukla

Abstract:

Little information is available about the development of psychological well being over time among women who have been undergoing treatment for breast cancer. The aim of this study was to identify the trajectories of depression anxiety and stress among women with early-stage breast cancer. Of the 48 Indian women with newly diagnosed early-stage breast cancer recruited from surgical oncology unit, 39 completed an interview and were assessed for depression anxiety and stress (Depression Anxiety Stress Scale-DASS 21) before their first course of chemotherapy (baseline) and follow up interviews at 3, 6 and 9 months thereafter. Growth mixture modeling was used to identify distinct trajectories of Depression Anxiety and Stress symptoms. Logistic Regression analysis was used to evaluate the characteristics of women in distinct groups. Most women showed mild to moderate level of depression and anxiety (68%) while normal to mild level of stress (71%). But one in 11 women was chronically anxious (9%) and depressed (9%). Young age, having a partner, shorter education and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong nine months after diagnosis. By looking beyond the mean, it was found that several socio-demographic and treatment factors characterized the women whose depression, anxiety and stress level remained severe even nine months after diagnosis. The results suggest that support provided to cancer patients should have a special focus on a relatively small group of patient most in need.

Keywords: psychological well being, growth mixture modeling, logistic regression analysis, socio-demographic factors

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3521 Assessing the Impact of Pharmacist-Led Medication Therapy Management on Treatment Adherence and Clinical Outcomes in Cancer Patients: A Prospective Intervention Study

Authors: Omer Ibrahim Abdallh Omer

Abstract:

Cancer patients often face complex medication regimens, leading to challenges in treatment adherence and clinical outcomes. Pharmacist-led medication therapy management (MTM) has emerged as a potential solution to optimize medication use and improve patient outcomes in oncology settings. In this prospective intervention study, we aimed to evaluate the impact of pharmacist-led MTM on treatment adherence and clinical outcomes among cancer patients. Participants were randomized to receive either pharmacist-led MTM or standard care, with assessments conducted at baseline and follow-up visits. Pharmacist interventions included medication reconciliation, adherence counseling, and personalized care plans. Our findings reveal that pharmacist-led MTM significantly improved medication adherence rates and clinical outcomes compared to standard care. Patients receiving pharmacist interventions reported higher satisfaction levels and perceived value in pharmacist involvement in their cancer care. These results underscore the critical role of pharmacists in optimizing medication therapy and enhancing patient-centered care in oncology settings. Integration of pharmacist-led MTM into routine cancer care pathways holds promise for improving treatment outcomes and quality of life for cancer patients.

Keywords: cancer, medications adherence, medication therapy management, pharmacist

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3520 Early Diagnosis and Treatment of Cancer Using Synthetic Cationic Peptide

Authors: D. J. Kalita

Abstract:

Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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3519 Hounsfield-Based Automatic Evaluation of Volumetric Breast Density on Radiotherapy CT-Scans

Authors: E. M. D. Akuoko, Eliana Vasquez Osorio, Marcel Van Herk, Marianne Aznar

Abstract:

Radiotherapy is an integral part of treatment for many patients with breast cancer. However, side effects can occur, e.g., fibrosis or erythema. If patients at higher risks of radiation-induced side effects could be identified before treatment, they could be given more individual information about the risks and benefits of radiotherapy. We hypothesize that breast density is correlated with the risk of side effects and present a novel method for automatic evaluation based on radiotherapy planning CT scans. Methods: 799 supine CT scans of breast radiotherapy patients were available from the REQUITE dataset. The methodology was first established in a subset of 114 patients (cohort 1) before being applied to the whole dataset (cohort 2). All patients were scanned in the supine position, with arms up, and the treated breast (ipsilateral) was identified. Manual experts contour available in 96 patients for both the ipsilateral and contralateral breast in cohort 1. Breast tissue was segmented using atlas-based automatic contouring software, ADMIRE® v3.4 (Elekta AB, Sweden). Once validated, the automatic segmentation method was applied to cohort 2. Breast density was then investigated by thresholding voxels within the contours, using Otsu threshold and pixel intensity ranges based on Hounsfield units (-200 to -100 for fatty tissue, and -99 to +100 for fibro-glandular tissue). Volumetric breast density (VBD) was defined as the volume of fibro-glandular tissue / (volume of fibro-glandular tissue + volume of fatty tissue). A sensitivity analysis was performed to verify whether calculated VBD was affected by the choice of breast contour. In addition, we investigated the correlation between volumetric breast density (VBD) and patient age and breast size. VBD values were compared between ipsilateral and contralateral breast contours. Results: Estimated VBD values were 0.40 (range 0.17-0.91) in cohort 1, and 0.43 (0.096-0.99) in cohort 2. We observed ipsilateral breasts to be denser than contralateral breasts. Breast density was negatively associated with breast volume (Spearman: R=-0.5, p-value < 2.2e-16) and age (Spearman: R=-0.24, p-value = 4.6e-10). Conclusion: VBD estimates could be obtained automatically on a large CT dataset. Patients’ age or breast volume may not be the only variables that explain breast density. Future work will focus on assessing the usefulness of VBD as a predictive variable for radiation-induced side effects.

Keywords: breast cancer, automatic image segmentation, radiotherapy, big data, breast density, medical imaging

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3518 Patterns of Malignant and Benign Breast Lesions in Hail Region: A Retrospective Study at King Khalid Hospital

Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

Abstract:

Background and Objectives: Breast carcinoma is the most common cancer of females in Hail region, accounting for 31% of all diagnosed cancer cases followed by thyroid carcinoma (25%) and colorectal carcinoma (13%). Methods: In the present retrospective study, all cases of breast lesions received at the histopathology department in King Khalid Hospital, Hail, during the period from May 2011 to April 2016 have been retrieved from department files. For all cases, a trucut biopsy, lumpectomy, or modified radical mastectomy was available for histopathologic diagnosis, while 105/140 (75%) had, as well, preoperative fine needle aspirates (FNA). Results: 49 cases out of 140 (35%) breast lesions were carcinomas: 44/49 (89.75%) was invasive ductal, 2/49(4.1%) invasive lobular carcinomas, 1/49(2.05%) intracystic low grade papillary carcinoma and 2/49 (4.1%) ductal carcinoma in situ (DCIS). Mean age for malignant cases was 45.06 (+/-10.58): 32.6% were below the age of 40 and 30.6 below 50 years, 18.3% below 60 and 16.3% below 70 years. For the benign group, mean age was 32.52 (+/10.5) years. Benign lesions were in order of frequency: 34 fibroadenomas, 14 fibrocystic disease, 12 chronic mastitis, five granulomatous mastitis, three intraductal papillomas, and three benign phyllodes tumor. Tubular adenoma, lipoma, skin nevus, pilomatrixoma, and breast reduction specimens constituted the remaining specimens. Conclusion: Breast lesions are common in our series and invasive carcinoma accounts for more than 1/3rd of the lumps, with 63.2% incidence in pre-menopausal ladies, below the age of 50 years. FNA as a non-invasive procedure, proved to be an effective tool in diagnosing both benign and malignant/suspicious breast lumps and should continue to be used as a first assessment line of palpable breast masses.

Keywords: age incidence, breast carcinoma, fine needle aspiration, hail region

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3517 Differences in Patient Satisfaction Observed between Female Japanese Breast Cancer Patients Who Receive Breast-Conserving Surgery or Total Mastectomy

Authors: Keiko Yamauchi, Motoyuki Nakao, Yoko Ishihara

Abstract:

The increase in the number of women with breast cancer in Japan has required hospitals to provide a higher quality of medicine so that patients are satisfied with the treatment they receive. However, patients’ satisfaction following breast cancer treatment has not been sufficiently studied. Hence, we investigated the factors influencing patient satisfaction following breast cancer treatment among Japanese women. These women underwent either breast-conserving surgery (BCS) (n = 380) or total mastectomy (TM) (n = 247). In March 2016, we conducted a cross-sectional internet survey of Japanese women with breast cancer in Japan. We assessed the following factors: socioeconomic status, cancer-related information, the role of medical decision-making, the degree of satisfaction regarding the treatments received, and the regret arising from the medical decision-making processes. We performed logistic regression analyses with the following dependent variables: extreme satisfaction with the treatments received, and regret regarding the medical decision-making process. For both types of surgery, the odds ratio (OR) of being extremely satisfied with the cancer treatment was significantly higher among patients who did not have any regrets compared to patients who had. Also, the OR tended to be higher among patients who chose to play a wanted role in the medical decision-making process, compared with patients who did not. In the BCS group, the OR of being extremely satisfied with the treatment was higher if, at diagnosis, the patient’s youngest child was older than 19 years, compared with patients with no children. The OR was also higher if patient considered the stage and characteristics of their cancer significant. The OR of being extremely satisfied with the treatments was lower among patients who were not employed on full-time basis, and among patients who considered the second medical opinions and medical expenses to be significant. These associations were not observed in the TM group. The OR of having regrets regarding the medical decision-making process was higher among patients who chose to play a role in the decision-making process as they preferred, and was also higher in patients who were employed on either a part-time or contractual basis. For both types of surgery, the OR was higher among patients who considered a second medical opinion to be significant. Regardless of surgical type, regret regarding the medical decision-making process decreases treatment satisfaction. Patients who received breast-conserving surgery were more likely to have regrets concerning the medical decision-making process if they could not play a role in the process as they preferred. In addition, factors associated with the satisfaction with treatment in BCS group but not TM group included the second medical opinion, medical expenses, employment status, and age of the youngest child at diagnosis.

Keywords: medical decision making, breast-conserving surgery, total mastectomy, Japanese

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3516 Comparison of the Curvizigzag Incision with Transverse Stewart Incision in Women Undergoing Modified Radical Mastectomy for Carcinoma Breast

Authors: John Joseph S. Martis, Rohanchandra R. Gatty, Aaron Jose Fernandes, Rahul P. Nambiar

Abstract:

Introduction: Surgery for breast cancer is either mastectomy or breast conservation surgery. The most commonly used incision for modified radical mastectomy is the transverse Stewart incision. But this incision may have the disadvantage of causing disparity between the closure lines of superior and inferior skin flaps in mastectomy and can cause overhanging of soft tissue below and behind the axilla. The curvizigzag incision, on principle, may help in this regard and can prevent scar migration beyond the anterior axillary line. This study aims to compare the two incisions in this regard. Methods: 100 patients with cancer of breast were included in the study after satisfying inclusion and exclusion criteria. They underwent surgery at Father Muller Medical College, Mangalore, India, between November 2019 to September 2021. The patients were divided into two groups. Group A patients were subjected to modified radical mastectomy with curvizigzag incision and group B patients with transverse Stewart incision. Results: Seroma on postoperative day1, day 2 was 0% in both the groups. Seroma on postoperative day 30 was present in 14% of patients in group B. 60% of patients in group B had sag of soft tissue below and behind the axilla, and none of the patients in group A had this problem. In 64% of the patients in group B, the incision crossed the anterior axillary fold, 64% of the patients in group B had tension in the incision site while approximation of the skin flaps. Conclusion: Curvizigzag incision is statistically better with lesser complications when compared to the transverse Stewart incision for modified radical mastectomy for carcinoma breast.

Keywords: breast cancer, curvizigzag incision, transverse Stewart incision, seroma, modified radical mastectomy

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3515 Variations in Breast Aesthetic Reconstruction Rates between Asian and Caucasian Patients Post Mastectomy in a UK Tertiary Breast Referral Centre: A Five-Year Institutional Review

Authors: Wisam Ismail, Chole Wright, Elizabeth Baker, Cathy Tait, Mohamed Salhab, Richard Linforth

Abstract:

Background: Post-mastectomy breast reconstruction is an important treatment option for women with breast cancer with psychosocial, emotional and quality of life benefits. Despite this, Asian patients are one-fifth as likely as Caucasian patients to undergo reconstruction after mastectomy. Aim: This study aimed to assess the difference in breast reconstruction rates between Asian and Caucasian patients treated at Bradford Teaching Hospitals between May 2011 – December 2015.The long-term goal is to equip healthcare professionals to improve breast cancer treatment outcome by increasing breast reconstruction rates in this sub-population. Methods: All patients undergoing mastectomy were identified using a prospectively collected departmental database. Further data was obtained via retrospective electronic case note review. Bradford city population is about 530.000 by the end of 2015, with 67.44% of the city's population was White ethnic groups and 26.83% Asian Ethnic Groups (UK population consensus). The majority of Asian population speaks Urdu, hence an Urdu speaking breast care nurse was appointed to facilitate communications and deliver a better understanding of the reconstruction options and pathways. Statistical analysis was undertaken using the SAS program. Patients were stratified by age, self-reported ethnicity, axillary surgery and reconstruction. Relative odds were calculated using univariate and multivariate logistic regression analyses with adjustment for known confounders. An Urdu speaking breast care nurse was employed throughout this period to facilitate communication and patient decision making. Results: 506 patients underwent Mastectomy over 5 years. 72 (14%) Asian v. 434 (85%) Caucasian. Overall median age is 64 years (SD1.1). Asian median age is 62 (SD0.9), versus Caucasian 65 (SD1.2). Total axillary clearance rate was 30% (42% Asian v.30% Caucasian). Overall reconstruction rate was 126 patients (28.9%).Only 6 of 72 Asian patients (<1%) underwent breast reconstruction versus 121of 434 Caucasian (28%) (p < 0.04), Odds ratio 0.68, (95% confidence interval 0.57-0.79). Conclusions: There is a significant difference in post-mastectomy reconstruction rates between Asian and Caucasian patients. This difference is likely to be multi-factorial. Higher rates of axillary clearance in Asian patients might suggest later disease presentation and/or higher rates of subsequent adjuvant therapy, both of which, can impact on the suitability of breast reconstruction. Strategies aimed at reducing racial disparities in breast reconstruction should include symptom awareness to enable earlier presentation and facilitated communication to ensure informed decision-making.

Keywords: aesthetic, Asian, breast, reconstruction

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3514 Automated Feature Detection and Matching Algorithms for Breast IR Sequence Images

Authors: Chia-Yen Lee, Hao-Jen Wang, Jhih-Hao Lai

Abstract:

In recent years, infrared (IR) imaging has been considered as a potential tool to assess the efficacy of chemotherapy and early detection of breast cancer. Regions of tumor growth with high metabolic rate and angiogenesis phenomenon lead to the high temperatures. Observation of differences between the heat maps in long term is useful to help assess the growth of breast cancer cells and detect breast cancer earlier, wherein the multi-time infrared image alignment technology is a necessary step. Representative feature points detection and matching are essential steps toward the good performance of image registration and quantitative analysis. However, there is no clear boundary on the infrared images and the subject's posture are different for each shot. It cannot adhesive markers on a body surface for a very long period, and it is hard to find anatomic fiducial markers on a body surface. In other words, it’s difficult to detect and match features in an IR sequence images. In this study, automated feature detection and matching algorithms with two type of automatic feature points (i.e., vascular branch points and modified Harris corner) are developed respectively. The preliminary results show that the proposed method could identify the representative feature points on the IR breast images successfully of 98% accuracy and the matching results of 93% accuracy.

Keywords: Harris corner, infrared image, feature detection, registration, matching

Procedia PDF Downloads 297
3513 Biocompatible Hydrogel Materials Containing Cytostatics for Cancer Treatment

Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

Abstract:

Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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3512 Trastuzumab Decorated Bioadhesive Nanoparticles for Targeted Breast Cancer Therapy

Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

Abstract:

Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

Procedia PDF Downloads 237
3511 Factors Associated with Recurrence and Long-Term Survival in Younger and Postmenopausal Women with Breast Cancer

Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

Abstract:

Background and Significance: Breast cancer is the most frequently diagnosed and leading cause of cancer death among women. This study aims to determine factors potentially predicting recurrence and long-term survival after the first recurrence in surgically treated patients between postmenopausal and younger women. Methods and Analysis: A retrospective cohort study was performed on 498 Thai women with invasive breast cancer, who had undergone mastectomy and been followed-up at Ubon Ratchathani Cancer Hospital, Thailand. We collected based on a systematic chart audit from medical records and pathology reports between January 1, 2002, and December 31, 2011. The last follow-up time point for surviving patients was December 31, 2016. A Cox regression model was used to calculate hazard ratios of recurrence and death. Findings: The median age was 49 (SD ± 9.66) at the time of diagnosis, 47% was post-menopausal women ( ≥ 51years and not experienced any menstrual flow for a minimum of 12 months), and 53 % was younger women ( ˂ 51 years and have menstrual period). Median time from the diagnosis to the last follow-up or death was 10.81 [95% CI = 9.53-12.07] years in younger cases and 8.20 [95% CI = 6.57-9.82] years in postmenopausal cases. The recurrence-free survival (RFS) for younger estimates at 1, 5 and 10 years of 95.0 %, 64.0% and 58.93% respectively, appeared slightly better than the 92.7%, 58.1% and 53.1% for postmenopausal women [HRadj = 1.25, 95% CI = 0.95-1.64]. Regarding overall survival (OS) for younger at 1, 5 and 10 years were 97.7%, 72.7 % and 52.7% respectively, for postmenopausal patients, OS at 1, 5 and 10 years were 95.7%, 70.0% and 44.5 respectively, there were no significant differences in survival [HRadj = 1.23, 95% CI = 0.94 -1.64]. Multivariate analysis identified five risk factors for negatively impacting on survival were triple negative [HR= 2.76, 95% CI = 1.47-5.19], Her2-enriched [HR = 2.59, 95% CI = 1.37-4.91], luminal B [HR = 2.29, 95 % CI=1.35-3.89], not free margin [HR = 1.98, 95%CI=1.00-3.96] and patients who received only adjuvant chemotherapy [HR= 3.75, 95% CI = 2.00-7.04]. Statistically significant risks of overall cancer recurrence were Her2-enriched [HR = 5.20, 95% CI = 2.75-9.80], triple negative [HR = 3.87, 95% CI = 1.98-7.59], luminal B [HR= 2.59, 95% CI = 1.48-4.54,] and patients who received only adjuvant chemotherapy [HR= 2.59, 95% CI = 1.48-5.66]. Discussion and Implications: Outcomes from this studies have shown that postmenopausal women have been associated with increased risk of recurrence and mortality. As the results, it provides useful information for planning the screening and treatment of early-stage breast cancer in the future.

Keywords: breast cancer, menopause status, recurrence-free survival, overall survival

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