• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6121-6128
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• 2012

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.717-722
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• 2013

Background: Breast cancer is the most common cancer among women worldwide. The aim of this study was to investigate the relationship between tumor size and axillary lymph node involvement (ALNI) in patients with invasive lesions, to find the best candidates for a full axillary dissection. Additionally, we evaluated the association between tumor size and invasive behavior. The study was based on data from 789 patients with histopathologically proven invasive breast cancer diagnosed in Shohada University hospital in Tehran, Iran (1993-2009). Cinical and histopathological characteristics of tumors were collected. Patients were divided into 6 groups according to primary tumor size: group I ($0.1-{\leq}1cm$), II ($1.1-{\leq}2cm$), III ($2.1-{\leq}3cm$), IV ($3.1-{\leq}4cm$), V ($4.1-{\leq}5cm$) and VI (>5cm). The mean(${\pm}SD$) size of primary tumor at the time of diagnosis was $3.59{\pm}2.69$ cm that gradually declined during the course of study. There was a significant correlation between tumor size and ALNI (p<0.001). A significant positive correlation between primary tumor size and involvement of surrounding tissue was also found (p<0.001). The mean number of LNI in group VI was significantly higher than other groups (p<0.05). We observed more involvement of lymph nodes, blood vessels, skin and areola-nipple tissue with increase in tumor size. We found 15.3% overall incidence of ALNI in tumors ${\leq}2cm$, indicating the need for more investigation to omit full axillary lymph node dissection with an acceptable risk for tumors below this diameter. While in patients with tumors ${\geq}2cm$, 84.3% of them had nodal metastases, so the best management for this group would be a full ALND. Tumor size is a significant predictor of ALNM and involvement of surrounding tissue, so that an exact estimation of the size of primary tumor is necessary prior to surgery to make the best decision for management of patients with invasive breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1973-1978
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• 2016

Background: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast. Materials and Methods: Formalin-fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes. Results. Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1% ) and non-luminal HER2+ (6.3%). Conclusions. The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.

• Molecules and Cells
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• v.39 no.3
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• pp.258-265
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• 2016

In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.141-141
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• 2003

Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer, including the degrees of invasion and tumor recurrence. We previously showed that p38 MAPK is a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells (Cancer Res.: 63, 5454-5461, 2003).(omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.170.2-170.2
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• 2003

Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer, including the degrees of invasion and tumor recurrence. We previously showed that p38 MAPK is a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells (Cancer Res: 63, 5454-5461, 2003). In this study, we further investigated the role of p38 MARK pathway in the induction of metastatic potential in MCF10A cells as a "gain of function" study. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1231-1233
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• 2012

Objective: The aim of this study was to explore the expression of DLC-l in breast carcinoma and any association with tumor metastasis. Methods: 51 surgical specimens of human breast carcinoma, divided into high invasive and low invasive groups according to their clinicopathological features, 30 cases of adjacent normal tissue and 28 benign breast lesions were examined by qRT-PCR for expression of DLC-1. Results: Expression level of DLC-1 in adjacent normal tissue and benign breast lesion specimens was higher than that in breast carcinoma (P<0.0001); the values in the high invasive group with synchronous metastases were also lower than in the low invasive group (P=0.0275). The correlation between DLC-1 expression level and tumor progression and metastasis of breast cancer was negative. Conclusion: As an anti-oncogene, DLC-1 could play an important part in breast carcinoma occurrence, progression, invasiveness and metastasis. Detecting the changes of the expression of DLC-1 in the breast carcinoma may contribute to earlier auxiliary diagnosis of invasiveness, metastasis and recrudescence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5539-5544
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• 2014

Background: To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. Materials and Methods: A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Results: Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241(7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173(16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Conclusions: Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype.

• Journal of the Korean Society of Radiology
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• v.79 no.5
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• pp.259-263
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• 2018

A 52-year-old male complained of a painless, firm, and slow-growing mass in his right breast outer portion. The chest CT revealed a 3.3 cm-sized oval shaped, microlobulated, mild enhancing mass. Ultrasound showed a microlobulated marginated heterogeneous hypoechoic mass with internal vascularity and calcifications in the mass. On the ultrasound-guided core needle biopsy, the mass was confirmed as a benign granular cell tumor (GCT). The patient transferred to another hospital and underwent surgical removal of the lesion. GCT of the breast is uncommon and mostly benign neoplasm to originate from Schwann cell. Clinical and radiologic features of GCTs, including CT and ultrasound images, mimic malignancy and make diagnosis of GCT more difficult. The CT images of GCTs are much rarely reported. Physicians and radiologists must be aware of radiologic characteristics of this rare benign tumor for male breast, to avoid misdiagnosis this tumor for breast malignancy and overtreat.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.311-317
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• 2004

Purpose: The purpose of this study was to determine the utility of tumor marker CA 15-3 in the following: the diagnosis of breast cancer relapse after curative mastectomy, and the differentiation or the value of tumor marker by site of metastases. Materials and Methods: Two hundred two patients (median age 48 years) with breast cancer included in the follow-up after curative mastectomy. The tumor marker CA 15-3 was determined by IRMA (CIS BIO INTERNATIONAL, France). Test values > 30 U/ml were considered elevated (positive). Results: Among 202 patients, recurrent diseases were found in 16 patients. CA 15-3 was elevated in 5 of 16 patients with recurrences. There was no false-positive patient who had elevated CA 15-3. Sensitivity and specificity of CA 15-3 for detection of breast cancer recurrence were 31%, and 100%. CA 15-3 was elevated in all of the 4 patients with liver metastases. CA 15-3 was elevated in none of the patients who relapsed with metastasis to bone-only or contralateral breast-only. Conclusion: The tumor marker CA 15-3 in the detection of breast cancer relapse after curative mastectomy is specific, but not sensitive. However, it is useful to rule out liver metastases of breast cancer, which indicates bad prognosis.