• Journal of Bone Metabolism
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• v.25 no.4
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• pp.251-266
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• 2018

Background: The causal networks among genes that are commonly expressed in osteoblasts and during bone metastasis (BM) of breast cancer (BC) are not well understood. Here, we developed a machine learning method to obtain a plausible causal network of genes that are commonly expressed during BM and in osteoblasts in BC. Methods: We selected BC genes that are commonly expressed during BM and in osteoblasts from the Gene Expression Omnibus database. Bayesian Network Inference with Java Objects (Banjo) was used to obtain the Bayesian network. Genes registered as BC related genes were included as candidate genes in the implementation of Banjo. Next, we obtained the Bayesian structure and assessed the prediction rate for BM, conditional independence among nodes, and causality among nodes. Furthermore, we reported the maximum relative risks (RRs) of combined gene expression of the genes in the model. Results: We mechanistically identified 33 significantly related and plausibly involved genes in the development of BC BM. Further model evaluations showed that 16 genes were enough for a model to be statistically significant in terms of maximum likelihood of the causal Bayesian networks (CBNs) and for correct prediction of BM of BC. Maximum RRs of combined gene expression patterns showed that the expression levels of UBIAD1, HEBP1, BTNL8, TSPO, PSAT1, and ZFP36L2 significantly affected development of BM from BC. Conclusions: The CBN structure can be used as a reasonable inference network for accurately predicting BM in BC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2225-2229
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• 2013

Background: As data on the relation between obesity and lymph node ratio are missing in the literature, we here aimed to assess the impact of obesity on this parameter and other clinicopathological features of breast cancer cases and patient survival. Materials and Methods: Medical data of 646 patients, all referred to two centers in Tehran, Iran, were reviewed. Factors that showed significant association on univariate analysis were entered in a regression model. Kaplan-Meier and Cox-regression were employed for survival analysis. Results: Obesity was correlated with the expression of estrogen and progesterone receptor (p=0.004 and p=0.039, respectively), metastasis to axillary lymph nodes (p=0.017), higher lymph node rate (p<0.001) and larger tumor size (p<0.001). The effect of obesity was stronger in premenopausal women. There was no association between obesity and expression of human epidermal growth factor receptor. Three factors showed independent association with BMI on multivariate analysis; tumor size, estrogen receptor and lymph node ratio. Obesity was predictive of shorter disease-free survival with a hazard ratio of 3.324 (95%CI: 1.225-9.017) after controlling for the above-mentioned variables. Conclusions: The findings of this study support the idea that obese women experience more advanced disease with higher axillary lymph node ratio, and therefore higher stage at the time of diagnosis. Furthermore, obesity was associated with poorer survival independent of lymph node rate.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4645-4649
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• 2012

Metaplastic breast carcinoma (MpBC) is a rare disease entity, accounting for less than 1% of all breast carcinomas. Furthermore, it is a heterogenous disease with different subgroups, including malignant epithelial (carcinoma) and stromal (sarcoma) features. Here we evaluated, retrospectively, 14 female MpBC patients admitted to Ankara Oncology Training and Research Hospital between 2005 and 2011. Median age was 45.5 (range:16.0-76.0) and tumor size 57.5 mm (range: 20.0-80.0 mm). Histopathological subtypes were as follows: 5 carcinosarcoma, 5 squamous and 4 adenosquamous carcinoma. All but one with upfront lung metastasis, had their primary breast tumor operated. Axillary lymph nodes were involved in 64.3%. The most common sites of metastasis were lungs and brain. Chemotherapy including antracycline, taxane and even platinium was planned for adjuvant, neoadjuvant and palliative purposes in 9, 3 and 1 patient, respectively. Median cycles of chemotherapy was 6 (range:4-8). Median follow-up of the patients was 52 months (95%CI 10.4-93.6 month). Median 3 year progression free survival (PFS) and overall survival (OS) in this patients cohort were 33% and 56%, respectively. In conclusion, MpBC is a rare and orphan disease without standardized treatment approaches and the prognosis is poor so that larger studies to investigate different treatment schedules are urgently needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2593-2596
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• 2016

Background: Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. In this study, we retrospectively evaluated the clinicopathological features, treatment options and overall survival in Kurdish MBC cases. Materials and Methods: Seventeen MBC were referred to Department of Radiation Oncology in Imam Reza Hospital, Kermanshah, Iran, between 2010 and 2016. Immunohistochemical analysis was performed for ER, PR and Her2 biomarkers and FISH for those with Her2 2+. Median follow-up period was 30 months (2-65 months). We excluded from the study patients who did not have follow-up after initial diagnosis. Treatment methods were chemotherapy, radiotherapy, hormonal therapy, target therapy and palliative care. Survival was estimated by the Kaplan Meier method (Prism 5). Results: The mean age at diagnosis was $49.24{\pm}17$ years (range, 24-85 years). Grade II was the most grade in MBC (65%). Fourteen patients (82%) had invasive ductal carcinoma, one (6%) had ductal carcinoma in situ and 2 (12%) had invasive papillary. ER, PR and Her2 were significantly positive in 14/17, 8/17 and 2/17 cases, respectively. The treatment included modified radical mastectomy for most patients. Chemotherapy with TAC and CEF regimens was delivered to 15/17 cases. Tamoxifen therapy was delivered to 14/17 cases. Three stage IV patients received Avestin and two with Her2 3+ were given Trastuzumab (Herceptin). Patients received adjuvant radiotherapy following surgery and chemotherapy. The site of metastasis was the bone in 2 cases, lung in 1 case and liver in 1 case. Zoledronic acid (Zometa) was prescribed for patients with bone metastasis. Five-year overall survival rate was 64%. Conclusions: MBC is rare. Thus, we need larger studies are in collaboration with several research centers in the field of breast cancer. ER positive, grade II of invasive ductal carcinoma, stage II and right side happened more with MBC. Overall survival is similar to other studies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.132-137
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• 2014

Purpose: To evaluate non-sentinel lymph node (LN) status after sentinel lymph node biopsy (SNB) in patients with breast cancer and to identify the predictive factors for disease failure. Materials and Methods: From January 2006 to December 2007, axillary lymph node (ALN) dissection after SNB was performed for patients with primary invasive breast cancer who had no clinical evidence of LN metastasis. A total of 320 patients were treated with breast-conserving surgery and radiotherapy. Results: The median age of patients was 48 years, and the median follow-up time was 72.8 months. Close resection margin (RM) was observed in 13 patients. The median number of dissected SNB was two, and that of total retrieved ALNs was 11. Sentinel node accuracy was 94.7%, and the overall false negative rate (FNR) was 5.3%. Eleven patients experienced treatment failure. Local recurrence, regional LN recurrence, and distant metastasis were identified in 0.9%, 1.9%, and 2.8% of these patients, respectively. Sentinel LN status were not associated with locoregional recurrence (p > 0.05). Close RM was the only significant factor for disease-free survival (DFS) in univariate and multivariate analysis. The 5-year overall survival, DFS, and locoregional DFS were 100%, 96.8%, and 98.1%, respectively. Conclusion: In this study, SNB was performed with high accuracy and low FNR and high locoregional control was achieved.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4233-4238
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• 2014

Background: The aim of this study was to investigate the relationship of body mass index with overall and progression-free survival as well as other prognostic factors of breast cancer in patients with non-metastatic breast cancer. Materials and Methods: We retrospectively reviewed 456 patients diagnosed with breast cancer in the Radiation Oncology department of Kayseri Teaching Hospital between 2005 and 2013. We investigated relationship of body mass index with prognosis and other prognostic factors. Results: The study included 456 patients (447 women and 9 men). Mean age at presentation was 55.6 years. Of the cases, 96.9% underwent modified radical mastectomy and 95.0% received chemotherapy, while 82.4% received radiotherapy and 60.0% were given hormone therapy. Body mass index was >25 mg/kg2 in 343 cases. Five- and 10-years overall survival rates were 77% and 58% whereas progression-free survival rates were 65% and 49%, respectively. In univariate analyses, factors including stage (p=0.046), tumor diameter (p=0.001), lymph node metastasis (p=0.006) and body mass index (p=0.030) were found to be significantly associated with overall survival, while perinodal involvement was found to be significantly associated with progression-free survival (p=0.018). In multivariate analysis, stage (p=0.032; OR: 3.8; 95% CI: 1.1-13), tumor diameter (p<0.000; OR: 0.0; 95% CI: 0.0-0.3), lymph node metastasis (p=0.005; OR: 0.0; 95% CI: 0.0-0.5) and BMI (p=0.027; OR: 0.02; 95% CI: 0.0-0.8) remained as significantly associated with OS. Conclusions: In our study, it was seen that overall survival time was shorter in underweight and obese patients when compared to normal weight patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5257-5261
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• 2012

Background: High incidence of breast cancer and its fatal effect has reached an alarming stage across the globe, including the third world countries. Many factors have been reported to be associated with the development of breast cancer but detailed structural and functional information is missing. CA 15-3 is one of the known potential tumor marker of breast cancer; however little is known about structure and functional site of this protein. Present study aims to investigate the functional role of CA 15-3 in breast cancer, especially in development and metastasis. Material and Methods: Hundred female breast cancer patients confirmed by histopathological reports were included in the study. Their physiological characters were recorded in a performa. Enzyme linked immunosorbent assay (ELISA) technique was used to estimate serum CA 15-3 level. Immunohistochemistry was done for estrogen (ER), progesterone (PR) and Her2/neu receptors expression. Results: The study revealed the details of physiological characteristics of female breast cancer. Mean age was $37.72{\pm}5.99$ and $55.05{\pm}7.28$ years and serum CA 15-3 (MUC1) level was $60.47{\pm}8.59$ and $63.17{\pm}4.58$ U/ml in pre and post-menopause respectively, and both groups of women had sedentary life style. Their receptor status especially of progesterone, estrogen and HER-2/neu were positive in 50% of premenopausal women and 65% of postmenopausal women. Conclusion: There are multiple physiological factors promoting breast cancer. High serum CA 15-3 level and hormonal imbalance of ER, PR and Her2/neu appears to be the main cause of breast cancer. It may be possible that the functional sites of these proteins may be altered which may increase the chances of metastasis in breast cancer.

• Korean Journal of Radiology
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• v.25 no.2
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• pp.146-156
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• 2024

Objective: Automated breast ultrasound (ABUS) is a relevant imaging technique for early breast cancer diagnosis and is increasingly being used as a supplementary tool for mammography. This study compared the performance of ABUS and handheld ultrasound (HHUS) in detecting and characterizing the axillary lymph nodes (LNs) in patients with breast cancer. Materials and Methods: We retrospectively reviewed the medical records of women with recently diagnosed early breast cancer (≤ T2) who underwent both ABUS and HHUS examinations for axilla (September 2017-May 2018). ABUS and HHUS findings were compared using pathological outcomes as reference standards. Diagnostic performance in predicting any axillary LN metastasis and heavy nodal-burden metastases (i.e., ≥ 3 LNs) was evaluated. The ABUS-HHUS agreement for visibility and US findings was calculated. Results: The study included 377 women (53.1 ± 11.1 years). Among 385 breast cancers in 377 patients, 101 had axillary LN metastases and 30 had heavy nodal burden metastases. ABUS identified benign-looking or suspicious axillary LNs (average, 1.4 ± 0.8) in 246 axillae (63.9%, 246/385). According to the per-breast analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of ABUS in predicting axillary LN metastases were 43.6% (44/101), 95.1% (270/284), 75.9% (44/58), 82.6% (270/327), and 81.6% (314/385), respectively. The corresponding results for HHUS were 41.6% (42/101), 95.1% (270/284), 75.0% (42/56), 82.1% (270/329), and 81.0% (312/385), respectively, which were not significantly different from those of ABUS (P ≥ 0.53). The performance results for heavy nodal-burden metastases were 70.0% (21/30), 89.6% (318/355), 36.2% (21/58), 97.3% (318/327), and 88.1% (339/385), respectively, for ABUS and 66.7% (20/30), 89.9% (319/355), 35.7% (20/56), 97.0% (319/329), and 88.1% (339/385), respectively, for HHUS, also not showing significant difference (P ≥ 0.57). The ABUS-HHUS agreement was 95.9% (236/246; Cohen's kappa = 0.883). Conclusion: Although ABUS showed limited sensitivity in diagnosing axillary LN metastasis in early breast cancer, it was still useful as the performance was comparable to that of HHUS.

• Korean Journal of Radiology
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• v.24 no.6
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• pp.498-511
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• 2023

Objective: To evaluate the diagnostic performance of chest computed tomography (CT)-based qualitative and radiomics models for predicting residual axillary nodal metastasis after neoadjuvant chemotherapy (NAC) for patients with clinically node-positive breast cancer. Materials and Methods: This retrospective study included 226 women (mean age, 51.4 years) with clinically node-positive breast cancer treated with NAC followed by surgery between January 2015 and July 2021. Patients were randomly divided into the training and test sets (4:1 ratio). The following predictive models were built: a qualitative CT feature model using logistic regression based on qualitative imaging features of axillary nodes from the pooled data obtained using the visual interpretations of three radiologists; three radiomics models using radiomics features from three (intranodal, perinodal, and combined) different regions of interest (ROIs) delineated on pre-NAC CT and post-NAC CT using a gradient-boosting classifier; and fusion models integrating clinicopathologic factors with the qualitative CT feature model (referred to as clinical-qualitative CT feature models) or with the combined ROI radiomics model (referred to as clinical-radiomics models). The area under the curve (AUC) was used to assess and compare the model performance. Results: Clinical N stage, biological subtype, and primary tumor response indicated by imaging were associated with residual nodal metastasis during the multivariable analysis (all P < 0.05). The AUCs of the qualitative CT feature model and radiomics models (intranodal, perinodal, and combined ROI models) according to post-NAC CT were 0.642, 0.812, 0.762, and 0.832, respectively. The AUCs of the clinical-qualitative CT feature model and clinical-radiomics model according to post-NAC CT were 0.740 and 0.866, respectively. Conclusion: CT-based predictive models showed good diagnostic performance for predicting residual nodal metastasis after NAC. Quantitative radiomics analysis may provide a higher level of performance than qualitative CT features models. Larger multicenter studies should be conducted to confirm their performance.