Search results for: MCF-7 human breast cancer

Authors: Aref Aasi, Sahar Ebrahimi Bajgani, Erfan Aasi

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

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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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Authors: Prathama Guha Chaudhuri, Arunima Datta, Ashis Mukhopadhyay

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Background: Visualization (guided imagery) is a set of techniques which induce relaxation and help people create positive mental images in order to reduce stress.It is relatively inexpensive and can even be practised by bed bound people. Studies have shown visualization to be an effective tool to improve cancer patients’ anxiety, depression and quality of life. The common images used with cancer patients in the developed world are those involving the individual’s body and its strengths. Since breast cancer patients in India are more family oriented and often their main concerns are the stigma of having cancer and subsequent isolation of their families, including their children, we figured that positive images involving acceptance and integration within family and society would be more effective for them. Method: Data was collected from 119 breast cancer patients on chemotherapy willing to undergo psychotherapy, with no history of past psychiatric illness. Their baseline stress, anxiety, depression and quality of life were assessed using validated tools. The participants were then randomly divided into three groups: a) those who received visualization therapy with standard imageries involving the body and its strengths (sVT), b) those who received visualization therapy using indigenous family oriented imageries (mVT) and c) a control group who received supportive therapy. There were six sessions spread over two months for each group. The psychological outcome variables were measured post intervention. Appropriate statistical analyses were done. Results:Both forms of visualization therapy were more effective than supportive therapy alone in reducing patients’ depression, anxiety and quality of life.Modified VT proved to be significantly more effective in improving patients’ anxiety and quality of life. Conclusion: Visualization is a valuable therapeutic option for reduction of psychological distress and improving quality of life of breast cancer patients.In order to be more effective, the images used need to be modified according to the sociocultural background and individual needs of the patients.

Keywords: breast cancer, visualization therapy, quality of life, anxiety, depression

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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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Authors: Yasser A. Ahmed, Juleen M Dickson, Evan S. Krystofiak, Julie A. Oliver

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Cancer cells urgently need folate to support their rapid division. Folate receptors (FR) are over-expressed on a wide range of tumor cells, including breast cancer cells. FR are distributed over the entire surface of cancer cells, but are polarized to the apical surface of normal cells. Targeting of cancer cells using specific surface molecules such as folate receptors may be one of the strategies used to kill cancer cells without hurting the neighing normal cells. The aim of the current study was to try a method of SEM detecting FR in a murine breast cancer cell model (4T1 cells) using secondary antibody conjugated to gold or gold-coated magnetite nanoparticles. 4T1 cells were suspended in RPMI medium witth FR antibody and incubated with secondary antibody for fluorescence microscopy. The cells were cultured on 30mm Thermanox coverslips for 18 hours, labeled with FR antibody then incubated with secondary antibody conjugated to gold or gold-coated magnetite nanoparticles and processed to scanning electron microscopy (SEM) analysis. The fluorescence microscopy study showed strong punctate FR expression on 4T1 cell membrane. With SEM, the labeling with gold or gold-coated magnetite conjugates showed a similar pattern. Specific labeling occurred in nanoparticle clusters, which are clearly visualized in backscattered electron images. The 4T1 tumor cell model may be useful for the development of FR-targeted tumor therapy using gold-coated magnetite nano-particles.

Keywords: cancer cell, nanoparticles, cell culture, SEM

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Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

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Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

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Authors: Cheuk Wing Lee, Kit Lun Yick, Sun Pui Ng, Joanne Yip

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Daily activities and exercise may result in large displacements of the breasts, which lead to breast pain and discomfort. Therefore, a proper bra design and fit can help to control excessive breast motion to prevent the over-stretching of the connective tissues. Nevertheless, bra fit problems, such as excessively high tension of the shoulder straps and a tight underband could have substantially negative effects on the wear comfort and health of the wearer. The purpose of this study is to, therefore, examine the effects of bra band tension on breast displacement. Usually, human wear trials are carried out, but there are inconsistencies during testing. Therefore, a soft manikin torso is used to examine breast displacement at walking speeds of 2.30 km/h and 4.08 km/h. The breast displacement itself is determined by using a VICON motion capture system. The 3D geometric changes of the underwire bra band tension and the corresponding control of breast movement are also analyzed by using a 3D handheld scanner along with Rapidform software. The results indicate that an appropriate bra band tension can help to reduce breast displacement and provide a comfortable angle for the underwire. The findings can be used by designers and bra engineers as a reference source to advance bra design and development.

Keywords: bra band, bra features, breast displacement, underwire angle

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

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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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Authors: D. J. Kalita

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

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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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Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

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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 1/3^rd 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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Authors: Keiko Yamauchi, Motoyuki Nakao, Yoko Ishihara

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

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

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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

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Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

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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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Authors: Layaly Ayoub, Mariana Ribeiro

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Introduction: Breast cancer is currently considered the leading cause of cancer-related deaths among women in Brazil. Mastectomy, essential in this treatment, often necessitates subsequent breast reconstruction to restore physical appearance and aid in the emotional and psychological recovery of patients. The choice between immediate or delayed reconstruction is influenced by factors such as the type and stage of cancer, as well as the patient's overall health. The decision between autologous breast reconstruction or implant-based reconstruction requires a detailed analysis of individual conditions and needs. Objectives: This study analyzes the techniques and indications used in post-mastectomy breast reconstruction. Methodology: Literature review conducted in the PubMed and SciELO databases, focusing on articles that met the inclusion and exclusion criteria and descriptors. Results: After mastectomy, breast reconstruction is commonly performed. It is necessary to determine the type of technique to be used in each case depending on the specific characteristics of each patient. The tissue expander technique is indicated for patients with sufficient skin and tissue post-mastectomy, who do not require additional radiotherapy, and who opt for a less complex surgery with a shorter recovery time. This procedure promotes the gradual expansion of soft tissues where the definitive implant will be placed. Both temporary and permanent expanders offer flexibility, allowing for adjustment in the expander size until the desired volume is reached, enabling the skin and tissues to adapt to the breast implant area. Conversely, autologous reconstruction is indicated for patients who will undergo radiotherapy, have insufficient tissue, and prefer a more natural solution. This technique uses the transverse rectus abdominis muscle (TRAM) flap, the latissimus dorsi muscle flap, the gluteal flap, and local muscle flaps to shape a new breast, potentially combined with a breast implant. Conclusion: In this context, it is essential to conduct a thorough evaluation regarding the technique to be applied, as both have their benefits and challenges.

Keywords: indications, post-mastectomy, breast reconstruction, techniques

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Authors: Mahsa Taghavi

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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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Authors: Hiroko Komatsu, Kaori Yagasaki

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Background: Cancer-related cognitive impairment is a common problem seen in cancer patients undergoing chemotherapy. Physical activity may show beneficial effects on the cognitive function in such patients. Therefore, we have developed a self-directed home yoga program for cancer patients with cognitive symptoms during chemotherapy. This program involves a DVD presenting a combination of yoga courses based on patient preferences to be practiced at home. This study was performed to examine the feasibility of this program. In addition, we also examined changes in cognitive function and quality of life (QOL) in these patients participating in the program. Methods: This prospective feasibility study was conducted in a 500-bed general hospital in Tokyo, Japan. The study population consisted of breast cancer patients undergoing chemotherapy as the initial therapy. This feasibility study used a convenience sample with estimation of recruitment rate in a single facility with the availability of trained nurses and physicians to ensure safe yoga intervention. The aim of the intervention program was to improve cognitive function by means of both physical and mental activation via yoga, consisting of physical practice, breathing exercises, and meditation. Information on the yoga program was provided as a booklet, with an instructor-guided group yoga class during the orientation, and a self-directed home yoga program on DVD with yoga logs. Results: The recruitment rate was 44.7%, and the study population consisted of 18 women with a mean age of 43.9 years. This study showed high rates of retention, adherence, and acceptability of the yoga program. Improvements were only observed in the cognitive aspects of fatigue, and there were serious adverse events during the program. Conclusion: The self-directed home yoga program discussed here was both feasible and safe for breast cancer patients showing cognitive symptoms during chemotherapy. The patients also rated the program as useful, interesting, and satisfactory. Participation in the program was associated with improvements in cognitive fatigue but not cognitive function.

Keywords: yoga, cognition, breast cancer, chemotherapy, quality of life

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Authors: Sara Malik, Andreea. S. Calude, Joseph Ulatowski

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This paper explores how speakers from New Zealand and Pakistan with breast cancer use violence metaphors to communicate the intensity of their experiences during various stages of illness. With the theoretical foundation in Conceptual Metaphor Theory and the use of Metaphor Identification Procedure for metaphor analysis, this study investigates how speakers with breast cancer use violence metaphors in different cultural contexts. it collected a corpus of forty-six personal narratives from New Zealand and thirty-six from Pakistan, posted between 2011 and 2023 on YouTube by breast cancer organisations, such as ‘NZ Breast Cancer Foundation’ and ‘Pink Ribbon Pakistan’. The data was transcribed using the Whisper AI tool and then curated to include only patients’ discourse, further organised into eight narrative topics: testing phase, treatment phase, remission phase, family support, campaigns and awareness efforts, government support and funding, general information and religious discourse. In this talk, it discuss two aspects of the use of violence metaphors, a) differences in the use of violence metaphors across various narrative topics, and b) lexical variations in the choice of such metaphors. The findings suggest that violence metaphors were used differently across various stages of illness experience. For instance, during the ‘testing phase,’ violence metaphors were employed to convey a sense of punishment as reflected in statements like, ‘Feeling like it was a death sentence, an immediate death sentence’ (NZ Example) and ‘Jese hi aap ko na breast cancer ka pata chalta hai logon ko yeh hona shuru ho jata hai ke oh bas ab to moat ka parwana mil gaya hai’ (Because as soon as you find out you have breast cancer people start to feel that you have received a death warrant) (PK Example). On the other hand, violence metaphor during the ‘treatment phase’ highlighted negative experiences related to chemotherapy as seen in statements like ‘The first lot of chemo I had was disastrous’ (NZ Example) and ‘...chemotherapy ke to, it's the worst of all, it's like a healing poison’ (chemotherapy, it's the worst of all, it's like a healing poison) (PK Example). Second, lexical variations revealed how ‘sunburn’ (a common phenomenon in the NZ) was used as a metaphor to describe the effects of radiotherapy, whereas in the discourse from Pakistan, a more general term, 'burn,' was used instead. In this talk, we will explore the possible reasons behind the different word choices made by speakers from both countries to describe the same process. This study contributes to understanding the use of violence metaphors across various narrative topics of the illness experience and explains how and why speakers from two different countries use lexical variations to describe the same process.

Keywords: metaphors, breast cancer discourse, cognitive linguistics, lexical variations, New zealand english, pakistani urdu

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Authors: Matthew Cardeiro, Amalia D. Ardeljan, Lexi Frankel, Dianela Prado Escobar, Catalina Molnar, Omar M. Rashid

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Introduction: Enterococci comprise the natural flora of nearly all animals and are ubiquitous in food manufacturing and probiotics. However, its role in the microbiome remains controversial. The gut microbiome has shown to play an important role in immunology and cancer. Further, recent data has suggested a relationship between gut microbiota and breast cancer. These studies have shown that the gut microbiome of patients with breast cancer differs from that of healthy patients. Research regarding enterococcus infection and its sequala is limited, and further research is needed in order to understand the relationship between infection and cancer. Enterococcus may prevent the development of breast cancer (BC) through complex immunologic and microbiotic adaptations following an enterococcus infection. This study investigated the effect of enterococcus infection and the incidence of BC. Methods: A retrospective study (January 2010- December 2019) was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using a Humans Health Insurance Database. International Classification of Disease (ICD) 9th and 10th codes, Current Procedural Terminology (CPT), and National Drug Codes were used to identify BC diagnosis and enterococcus infection. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), antibiotic treatment, and region of residence. Chi-squared, logistic regression, and odds ratio were implemented to assess the significance and estimate relative risk. Results: 671 out of 28,518 (2.35%) patients with a prior enterococcus infection and 1,459 out of 28,518 (5.12%) patients without enterococcus infection subsequently developed BC, and the difference was statistically significant (p<2.2x10⁻¹⁶). Logistic regression also indicated enterococcus infection was associated with a decreased incidence of BC (RR=0.60, 95% CI [0.57, 0.63]). Treatment for enterococcus infection was analyzed and controlled for in both enterococcus infected and noninfected populations. 398 out of 11,523 (3.34%) patients with a prior enterococcus infection and treated with antibiotics were compared to 624 out of 11,523 (5.41%) patients with no history of enterococcus infection (control) and received antibiotic treatment. Both populations subsequently developed BC. Results remained statistically significant (p<2.2x10-16) with a relative risk of 0.57 (95% CI [0.54, 0.60]). Conclusion & Discussion: This study shows a statistically significant correlation between enterococcus infection and a decrease incidence of breast cancer. Further exploration is needed to identify and understand not only the role of enterococcus in the microbiome but also the protective mechanism(s) and impact enterococcus infection may have on breast cancer development. Ultimately, further research is needed in order to understand the complex and intricate relationship between the microbiome, immunology, bacterial infections, and carcinogenesis.

Keywords: breast cancer, enterococcus, immunology, infection, microbiome

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Authors: Memnun Seven, Mine Bahar, Aygül Akyüz, Hatice Erdoğan

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Background: The workplace has been deemed a suitable location for educating many women at once about cancer screening. Objective: To determine how group education about early diagnostic methods for breast and cervical cancer affects women’s behavior and readiness to receive mammography and Pap smears. Methods: This semi-interventional study was conducted at a textile factory in Istanbul, Turkey. Female workers (n = 125) were included in the study. A participant identification form and knowledge evaluation form developed for this study, along with the trans-theoretical model, were used to collect data. A 45-min interactive group education was given to the participants. Results: Upon contacting participants 3 months after group education, 15.4% (n = 11) stated that they had since received a mammogram and 9.8% (n = 7) a Pap smear. As suggested by the trans-theoretical model, group education increased participants’ readiness to receive cancer screening, along with their knowledge of breast and cervical cancer. Conclusions: Group education positively impacted women’s knowledge of cancer and their readiness to receive mammography and Pap smears. Group education can therefore potentially create awareness of cancer screening tests among women and improve their readiness to receive such tests.

Keywords: cancer screening, educational intervention, participation, women

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Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

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Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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Authors: Jean Paul M. Milambo

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Purpose: Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown cardiovascular events in some developed countries. To date the data is sparce for evidence-based recommendations in African clinical settings due to lack of cancer registries, capacity building and surveillance systems. Therefore, this study was conducted to assess the feasibility of HyBeacon® probe genotyping adjunctive to standard care for timely prediction and diagnosis of Aromatase inhibitors (AIs) associated adverse events in breast cancer survivors in Africa. Methods: Cross sectional study was conducted to assess the knowledge of POCT among six African countries using online survey and telephonically contacted. Incremental cost effectiveness ratio (ICER) was calculated, using diagnostic accuracy study. This was based on mathematical modeling. Results: One hundred twenty-six participants were considered for analysis (mean age = 61 years; SD = 7.11 years; 95%CI: 60-62 years). Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that sensitivity was reported at 99% (95% CI: 94.55% to 99.97%), specificity at 89.44% (95% CI: 87.25 to 91.38%), PPV at 51% (95%: 43.77 to 58.26%), and NPV at 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that ICER was R7 044.55. Conclusion: POCT using HyBeacon® probe genotyping for AI-associated adverse events maybe cost effective in many African clinical settings. Integration of preventive measures for early detection and prevention guided by different subtype of breast cancer diagnosis with specific clinical, biomedical and genetic screenings may improve cancer survivorship. Feasibility of POCT was demonstrated but the implementation could be achieved by improving the integration of POCT within primary health cares, referral cancer hospitals with capacity building activities at different level of health systems. This finding is pertinent for a future envisioned implementation and global scale-up of POCT-based initiative as part of risk communication strategies with clear management pathways.

Keywords: breast cancer, diagnosis, point of care, South Africa, aromatase inhibitors

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Authors: Lakmali Anthony, Madeline Gillies

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Background Breast cancer (BC) is usually managed with surgical resection. Many outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO) such as Health-Related Quality of life (HRQoL) provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods Patients who had resection of BC in a regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Results Forty-six patients completed the survey. Clinically significant levels of FCR and emotional distress were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for BC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL for breast cancer. All psychosocial factors measured were associated with HRQoL. Conclusion HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative breast cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: breast cancer, surgery, quality of life, regional population

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Authors: Afrah Aladwani, Alexander Mullen, Mohammad AlRashidi, Omamah Alfarisi, Faisal Alterkit, Abdulwahab Aladwani, Asit Kumar, Emad Eldosouky

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Introduction: Trastuzumab is a HER-2 targeted humanized monoclonal antibody that significantly improves the therapeutic outcomes of metastatic and non-metastatic breast cancer. However, it is associated with increased risk of cardiotoxicity that ranges from mild decline in the cardiac ejection fraction to permanent cardiomyopathy. Concerns have been raised in treating eligible older patients. This study compares trastuzumab outcomes between two age cohorts in the Kuwait Cancer Control Centre (KCCC). Methods: In a prospective comparative observational study, 93 HER-2 positive breast cancer patients undergoing different chemotherapy protocols + trastuzumab were included and divided into two cohorts based on their age (˂60 and ≥60 years old). The baseline left ventricular ejection fraction (LVEF) was assessed and monitored every three months during trastuzumab treatment. Event of cardiotoxicity was defined as ≥10% decline in the LVEF from the baseline. The lower accepted normal limit of the LVEF was 50%. Results: The median baseline LVEF was 65% in both age cohorts (IQR 8% and 9% for older and younger patients respectively). Whereas, the median LVEF post-trastuzumab treatment was 51% and 55% in older and younger patients respectively (IQR 8%; p-value = 0.22), despite the fact that older patients had significantly lower exposure to anthracyclines compared to younger patients (60% and 84.1% respectively; p-value ˂0.001). 86.7% and 55.6% of older and younger patients, respectively, developed ≥10% decline in their LVEF from the baseline. Among those, only 29% of older and 27% of younger patients reached a LVEF value below 50% (p-value = 0.88). Statistically, age was the only factor that significantly correlated with trastuzumab induced cardiotoxicity (OR 4; p-value ˂0.012), but it did not increase the requirement for permanent discontinuation of treatment. A baseline LVEF value below 60% contributed to developing a post-treatment value below normal ranges (50%). Conclusion: Breast cancer patients aged 60 years and above in Kuwait were at 4-fold higher risk of developing ≥10% decline in their LVEF from the baseline than younger patients during trastuzumab treatment. Surprisingly, previous exposure to anthracyclines and multiple comorbidities were not associated with significant increased risk of cardiotoxicity.

Keywords: breast cancer, elderly, Trastuzumab, cardiotoxicity

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Authors: Ella Tyuryumina, Alexey Neznanov

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Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

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Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

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Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

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Authors: Vasudha Devi, Arul Amuthan, K. Narayanan, Praveen KS, Venkata Rao J

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Background: Siddha Medicine is one of the Indian traditional medical systems, in which the cancer disease is mentioned as 'putrunoi' which literally means the disease of growth like termite mound. There are number of formulations available for the treatment of cancer disease. Neeradi muthu vallathymezugu (NMV) and thamira kattu chendooram (TKC) are two drugs commonly prescribed by Siddha physicians. These drugs have been clinically reported to be safe and effective when given orally. Though these formulations are in practice for centuries, no efforts have been made to standardize them and explore their anti-cancer potential systematically. Objective: To compare the cytotoxic activity of NMV and TKC with doxorubicin using cancer cell lines. Materials and methods: For this study, ethanol extract of NMV was taken, whereas TKC was used as such. In vitro cytotoxic activity was evaluated by sulphorhodamine (SRB) assay against human hepatic cancer cells (HepG2), human breast cancer cells (MCF-7) and human cervical cancer cells [KeLa]. Doxorubicin was used as the standard. The SRB assay is based on the ability of cellular proteins to bind with sulphorhodamine-B. The number of live cells in drug treated cell lines directly affects the color formation in the assay, which is estimated calorimetrically by measuring the absorbance at 540 nm to calculate the cytotoxicity (inhibitory concentration - IC50 value) of the drug. Results: The IC50values of NMV, TKC and doxorubicin against HepG2 were 3.08 µg/ml, 20.21 µg/ml and 1.21µg/ml respectively. In MCF-7, it was 11.75 µg/ml, 17.67 µg/ml and 2.8µg/ml. In HeLa, the values were 24.76 µg/ml, 73.35 µg/ml and 1.12µg/ml. Conclusions: The study proves the possible anti-cancer potential of these two formulations. Compared to TKC, NMV showed good cytotoxic effect even at low dose. Human hepatic cancer cells responded well even at very low dose, when compared to other cancer cells. Though, cytotoxic potential of these compounds was found to be less compared to doxorubicin, the isolated lead compound may have the potential to be used as an anticancer drug clinically.

Keywords: Neeradi muthu vallathymezugu (Hydnocarpus laurifolia), thamira kattu chendooram, cytotoxicity, in-vitro, Siddha Medicine

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Authors: Zatil Athaillah, Anastasia Devi, Dian Muzdalifah, Wirasuwasti Nugrahani, Linar Udin

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During tempe fermentation, some chemical changes occurred and they contributed to sensory, appearance, and health benefits of soybeans. Many studies on health properties of tempe have specialized on their isoflavones. In this study, other components of tempe, particularly water soluble chemicals, was investigated for their biofunctionality. The study was focused on the ability to suppress MCF-7 breast cancer cell growth and antioxidant activity, as expressed by DPPH radical scavenging activity, total phenols and total flavonoids, of the water extracts. Fermentation time of tempe was extended up to 120 hr to increase the possibility to find the functional components. Extraction yield and soluble nitrogen content were also quantified as accompanying data. Our findings suggested that yield of water extraction of tempe increased as fermentation was extended up to 120 hr, except for a slight decrease at 72 hr. Water extracts of tempe showed inhibition of MCF-7 breast cancer cell growth, as shown by lower IC50 values when compared to control (unfermented soybeans). Among the varied fermentation timescales, 60-hr period showed the highest activity (IC50 of 8.7 ± 4.95 µg/ml). The anticancer activity of extracts obtained from different fermentation time was positively correlated with total soluble nitrogens, but less relevant with antioxidant data. During 48-72 hr fermentation, at which cancer suppression activity was significant, the antioxidant properties from the three assays were not higher than control. These findings indicated that water extracts of tempe from extended fermentation could inhibit breast cancer cell growth but further study to determine the mechanism and compounds that play important role in the activity should be conducted.

Keywords: tempe, anticancer, antioxidant, phenolic compounds

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Authors: N. Zarghami, M. Mohammadinejad, A. Akbarzadeh, Y. Pilehvar-Soltanahmadi, F. Zarghami

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Breast cancer is known to be the most common cancer in women. Cyclin D1 is a proto-oncogene and over expression of cyclin D1 is directly associated with tumorgenesis. Cyclin D1 is overexpressed in more than 50% of breast cancer cases. Curcumin is derived from turmeric (curcuma longa) and chrysin is a component that could be extracted from many plants and honey. These two plants derived compounds are believed to assist in inhibition of the cancer cells growth and reducing cyclin D1 expression. In this work, the hypothesis is to combine curcumin and chrysin in order to analyze the potential synergistic effect in inhibition of cell proliferation and down regulation of cyclin D1. In addition, use of PLGA-PEG to improve bioavailability of pure curcumin and chrysin, while reinforcing the potential effect of this combination. PLGA-PEG nanoparticles were synthesized and characterized with FT-IR and 1HNMR methods. Although morphological features were analyzed by SEM. Afterward curcumin and chrysin were encapsulated with synthesized PLGA-PEG and MTT-assay was performed to measure cytotoxicity effect of these plant constitutes. T-47D cells were treated with proper concentration of these constituents and Real-time PCR was carried out to evaluate cyclin D1 expression levels. Curcumin, chrysin and combination of curcumin –chrysin in intact and nano-capsulated form affected T-47D cells in time and dose dependent manner and the combination of these compounds had synergistic effects. Real-time PCR results, revealed that curcumin, chrysin and combination of curcumin-chrysin in pure and encapsulated form inhibited cyclin D1 expression. Compared to pure components, different concentrations of nano-curcumin, nano chrysin and nano-combination caused further decline in cyclin D12 expression by 5-11%, 8-22% and 6-18% respectively. Our results demonstrated that, combination of chrysin-curcumin had synergistic effect and nano capsulated form of this component had grater inhibition on cyclin D1 expression.

Keywords: breast cancer, cyclin D1, curcumin, chrysin, nanoparticles

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