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1.  Primary Follicular Lymphoma in a Male Breast: A Case Report 
Primary breast lymphoma (PBL) is a rare disease, particularly in males. Diffuse large B cell lymphoma is the most common PBL, while follicular lymphoma is less common. Furthermore, primary follicular lymphoma of a male breast is rarely reported. We report a male patient with primary follicular lymphoma of the breast and hepatocellular carcinoma (HCC). A 46-year-old man was diagnosed with liver cirrhosis secondary to chronic hepatitis B infection. Ten years later, he underwent segmentectomy of the liver due to HCC. Another 5 months later, he presented with a painless mass in the right chest wall. The mass was diagnosed as follicular lymphoma of the breast. The stage was IEA and he did not receive adjuvant therapy. Although only a few cases have been reported, lymphoma should be considered as a possible cause of breast mass, even in male patients.
PMCID: PMC3918521  PMID: 24520230
Breast; Follicular lymphoma; Hepatocellular carcinoma; Liver cirrhosis; Male
2.  Tubular Carcinoma of the Breast: Clinicopathologic Features and Survival Outcome Compared with Ductal Carcinoma In Situ 
Journal of Breast Cancer  2013;16(4):404-409.
Tubular carcinoma (TC) of the breast is an uncommon histological subtype of invasive breast cancer with an excellent prognosis compared with standard invasive ductal carcinoma. Recent studies suggested a possible precursor role for low grade ductal carcinoma in situ (DCIS) in the development of TC. The goal of this analysis was to understand the clinicopathologic features and outcomes of TC by comparing TC with DCIS.
A retrospective review identified 70 patients with TC and 1,106 patients with DCIS between 1995 and 2011. Student t-test and Fisher exact test were used to compare the clinicopathologic characteristics of TC patients with those of DCIS patients. The Kaplan-Meier method and Cox regression analysis were used to determine disease-free survival (DFS) rates.
Compared to DCIS, TC exhibited favorable clinicopathologic characteristics such as a lower nuclear grade (92.3%), higher expression of hormonal receptors (estrogen receptor-positive, 92.9%; progesterone receptor-positive, 87.0%), and less frequent overexpression of human epidermal growth receptor 2 (12.9%). DFS did not differ significantly between the TC and DCIS groups (5-year DFS, 100% vs. 96.7%; 10-year DFS, 92.3% vs. 93.3%; p=0.324), and cancer-specific deaths were not noted in either group. However, axillary lymph node involvement was observed in six (8.6%) of the 70 patients with TC. Three of these patients had small tumors (≤1 cm).
In our study cohort, TC was associated with an excellent prognosis and a low rate of lymph node metastasis. However, lymph nodes metastases were found even in patients with small tumors (≤1 cm). Axillary staging must be considered for all patients with TC of the breast.
PMCID: PMC3893342  PMID: 24454462
Breast neoplams; Ductal carcinoma in situ; Lymph nodes; Tubular
3.  Aromatase inhibitor-associated musculoskeletal symptoms: incidence and associated factors 
Arthralgia is the most common side effect in breast cancer patients receiving aromatase inhibitor (AI) therapy. Few studies have evaluated the risk factors, onset, and incidence of musculoskeletal pain in these patients. This study identifies the risk factors of AI-related severe arthralgia and their prevalence.
All the clinical and pathological records of postmenopausal patients diagnosed with invasive breast cancer using AI at Samsung Medical Center from January 2005 to November 2007 were reviewed. Multivariate logistic regression analyses were performed to evaluate the risk factors of AI-associated musculoskeletal symptoms (AIMSS) and factors associated with AI discontinuance.
Among 299 patients, 69 patients (23%) experienced musculoskeletal symptoms attributed to AI use. In multivariate logistic regression analysis, no statistically significant outcome was found to confirm the risk factors for the development of AIMSS. Among the 69 patients who experienced AI-associated musculoskeletal symptoms, 29 (39.7%) discontinued AI use. Multivariate logistic regression analyses revealed an association of prior tamoxifen use with discontinuance of AI (P < 0.01; odds ratio, 4.27; 95% confidence interval, 1.74 to 10.50).
Prior use of tamoxifen is related to discontinuation of AI due to AI-associated severe arthralgia. Special monitoring and proper pain control for these patients should be considered during the treatment period.
PMCID: PMC3834018  PMID: 24266010
Aromatase inhibitors; Aromatase inhibitor-associated musculoskeletal symptoms; Prior tamoxifen
4.  Adjuvant Chemotherapy and Survival of Elderly Korean Patients with Breast Carcinoma 
Journal of Breast Cancer  2012;15(3):296-305.
The available research work on types of treatment and the efficacy of adjuvant chemotherapy in older Korean patients is insufficient. Henceforth, this report assessed treatment patterns and the relationship between chemotherapy and survival in elderly Korean breast cancer patients.
We identified women over 55 years of age diagnosed with breast cancer from the period 1995 to 2006. Clinicopathologic features and treatment methods were compared for three groups divided on the basis of age: 55 to 59 years, 60 to 69 years, and over 70 years old. The effects of chemotherapy on survival were compared overall and individually for each group.
A total of 832 patients over 55 years of age were included in the present investigation. No statistical differences were observed between the three age groups in clinicopathologic features including tumor size, grade, and stage. However, patients in the elderly group received mastectomy more often when compared to the younger groups (p<0.001). In contrast, there was a decline in radiation treatment and chemotherapy with older age (p<0.001). Overall, patients who received chemotherapy had a significantly increased breast cancer specific survival and overall survival rate when compared to the non-chemotherapy groups (p=0.022). Among the estrogen receptor positive group, no statistical significance was achieved in the survival benefit of chemotherapy. However, in estrogen receptor-negative patients, overall, the chemotherapy groups showed a better survival rate than the non-chemotherapy patients and a similar trend was observed in each age group except in the group comprising of 70 years old patients.
This study describes the survival benefit of adjuvant chemotherapy in Korean patients over 55 years of age, especially in hormone receptor-negative patients. Hence, based on the results of the present report and considering the similarity of clinicopathologic features between age groups, it is proposed that age alone should not be a determinant factor of treatment methods.
PMCID: PMC3468783  PMID: 23091542
Aged; Breast; Carcinoma; Chemotherapy; Survival
5.  Long-Term Outcome of Internal Mammary Lymph Node Detected by Lymphoscintigraphy in Early Breast Cancer 
Journal of Breast Cancer  2012;15(1):98-104.
Internal mammary lymph node (IMLN) metastasis is an important prognostic indicator in breast cancer. However, the necessity of internal mammary sentinel lymph node biopsy for accurate staging, for choosing adjuvant treatment, and as a prognostic indicator, has remained controversial.
From January 2001 to December 2006, 525 female breast cancer patients underwent radical surgery after preoperative lymphatic scintigraphy. We retrospectively analyzed the follow-up results, recurrences, and deaths of all patients.
There was no significant difference in the clinicopathological characteristics between the axilla and the IMLN groups. The median follow-up period was 118.8 months (range, 7-122 months) in the axilla group and 107.7 months (range, 14-108 months) in the IMLN group. During the median follow-up period, the breast cancer-related death rate in the axilla group was 3.6%, which was not significantly different from that of the IMLN group (1.3%) (p=0.484). The five-year survival rates did not differ between the two groups (p=0.306). The overall recurrence rate and the locoregional recurrence rate also did not differ between the two groups (p=0.835 and p=0.582, respectively). The recurrence rate of IMLN (both ipsilateral and contralateral) metastasis was very low, accounting for 0.5% in the axilla group and 1.3% in the IMLN group (p=0.416).
The long-term follow-up results showed that there was no significant difference in both overall outcome and regional recurrence between the two groups. Therefore, the requirement for identification of nodal basins outside the axilla or IMLN sentinel biopsy should be reconsidered.
PMCID: PMC3318182  PMID: 22493635
Breast; Carcinoma; Internal mammary; Prognosis; Sentinel lymph node biopsy
8.  Neuronal Apoptosis Inhibitory Protein is Overexpressed in Patients with Unfavorable Prognostic Factors in Breast Cancer 
Journal of Korean Medical Science  2007;22(Suppl):S17-S23.
Neuronal apoptosis inhibitory protein (NAIP) is a recently identified inhibitor of apoptosis protein. However, the clinical relevance of NAIP expression is not completely understood. In an attempt to determine the clinical relevance of NAIP expression in breast cancer, the levels of NAIP and survivin expression were measured in 117 breast cancer samples and 10 normal breast tissues using quantitative reverse-transcriptase-polymerase chain reaction. While there was no evidence of NAIP expression in the normal breast tissue, NAIP was expressed in all breast cancer samples. The level of NAIP expression in breast cancer was significantly higher (257 times) than in the universal tumor control. There was a strong correlation between the level of NAIP expression and the level of survivin expression (p=0.001). The level of NAIP expression in patients with a large tumor (≥T2) and patients with an unfavorable histology (nuclear grade III) was significantly higher than in those patients with a small tumor (T1) and patients with a favorable histology (nuclear grade I, II) (p=0.026 and p=0.050, respectively). Although the level of NAIP expression was higher in patients with other unfavorable prognostic factors, it was not significant. The three-year relapse-free survival rate was not significantly the patients showing high NAIP expression and patients showing low NAIP expression (86.47±4.79% vs. 78.74±6.57%). Further studies should include the expressions of NAIP in a larger number of patients and for a longer period of follow-up to evaluate correlation with metastasis and treatment outcome. In conclusion, NAIP is overexpressed in breast cancer patients with unfavorable clinical features such as stage and tumor size, suggesting that NAIP would play a role in the disease manifestation.
PMCID: PMC2694398  PMID: 17923748
Breast Cancer; Neuronal Apoptosis Inhibitory rotein (NAIP); Apoptosis; Prognostic Factor; Clinical Relevance
9.  Immunoexpression of HBME-1, High Molecular Weight Cytokeratin, Cytokeratin 19, Thyroid Transcription Factor-1, and E-cadherin in Thyroid Carcinomas 
Journal of Korean Medical Science  2005;20(5):853-859.
To examine the immunohistochemical alterations associated with the histological dedifferentiation of thyroid carcinomas, we performed staining for HBME-1, high molecular weight cytokeratin (HCK), CK 19, thyroid transcription factor-1 (TTF-1) and E-cadherin (E-CD) on 125 various types of thyroid carcinomas. The HBME-1 staining was strong and diffuse in follicular carcinoma (FC), papillary carcinoma (PC), and poorly differentiated carcinoma (PDC), while it was rare in undifferentiated carcinoma (UC) as well as in benign lesions. Strong, diffuse staining for CK19 and HCK was predominantly found in PC, and these markers were not much found in other carcinomas. TTF-1 uniformly stained the tumor cells of all cases of PC, FC and Hurthle cell carcinoma (HC) and 42% of the PDC, while there was only focal staining in one case of the UC. Compared to the strong, diffuse reactivity in the benign lesions, E-CD staining was noted in 67% of PC, 80% of FC, 83% of HC, 58% of PDC and none of the UC. These results suggest that HBME-1 may be a marker for well-differentiated carcinomas while CK19 and HCK are phenotypic markers for papillary carcinoma. The loss or reduced expression of TTF-1 and E-CD may be markers for dedifferentiation.
PMCID: PMC2779285  PMID: 16224162
HBME-1 antigen; Keratin; thyroid nuclear factor 1; Cadherins; Thyroid Neoplasms
10.  E-cadherin and Cytokeratin Subtype Profiling in Effusion Cytology 
Journal of Korean Medical Science  2004;19(6):826-833.
Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic anti-gen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20- expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.
PMCID: PMC2816286  PMID: 15608393
Pleural Effusion; Ascites; Carcinoma; Mesothelioma; Neoplasms, Mesothelial; Cadherins; Keratin; Cytokeratin 20; Keratin 7
11.  Anticancer effect of silibinin on the xenograft model using MDA-MB-468 breast cancer cells 
The aim of this study is to know whether silibinin has an anticancer effect on triple negative breast cancer xenograft model using MDA-MB-468 cells.
To establish the xenograft model, we injected the MDA-MB-468 cells into female Balb/c-nude mice. After establishing a xenograft model, oral silibinin was administered to the tested mice in the way of 200 mg/kg for 45 days. The difference of mean tumor volume between silibinin fed mice and control mice was analyzed. The epidermal growth factor receptor (EGFR) phosphorylation in MDA-MB-468 cells was analyzed by Western blotting. The expression of VEGF, COX-2, and MMP-9 genes in tumor tissue was analyzed by real-time polymerase chain reaction (PCR).
In the xenograft model using MDA-MB-468 cells, we found that oral administration of silibinin significantly suppressed the tumor volume (silibinin treated mice vs. control mice; 230.3 ± 61.6 mm3 vs. 435.7 ± 93.5 mm3, P < 0.001). The phosphorylation of EGFR in MDA-MB-468 cells was inhibited by treatment with 50 µg/mL of silibinin. In real time-PCR analysis of tumor tissue obtained from sacrificed mice, the gene expression of MMP-9, VEGF, and COX-2 was 51.8%-80% smaller in silibinin group than that of control group and we can also verify the similar result using Western blotting analysis.
We verified that silibinin had anticancer effect on xenograft model of MDA-MB-468 cells in the way of preventing the phosphorylation of EGFR and eventually suppressed the production of COX-2, VEGF, and MMP-9 expression. Finally, the tumor volume of xenograft models was decreased after administration of Silibinin.
PMCID: PMC4196436  PMID: 25317410
Triple negative breast neoplasms; Silibinin; Xenograft
12.  Clinical Significance of the Axillary Arch in Sentinel Lymph Node Biopsy 
Journal of Breast Cancer  2014;17(3):244-249.
The axillary arch is an anomalous muscle that is not infrequently encountered during axillary sentinel lymph node biopsy (SLNB) of breast cancer patients. In this study, we aimed to investigate how often the axillary arch is found during SLNB and whether it affects the intraoperative sentinel lymph node (SLN) identification rate.
We retrospectively analyzed the correlation between the presence of the axillary arch and the SLN sampling failure rate during SLNB in 1,069 patients who underwent axillary SLNB for invasive breast cancer.
Of 1,069 patients who underwent SLNB, 79 patients (7.4%) had the axillary arch present. The SLNB failure rate was high when the patient's body mass index was ≥25 (p=0.026), when a single SLN mapping technique was used (p=0.012), and when the axillary arch was present (p<0.001). These three factors were also found to be statistically significant by multivariate analysis, and of these three factors, presence of the axillary arch most significantly increased the SLNB failure rate (hazard ratio, 10.96; 95% confidence interval, 4.42-27.21; p<0.001). Additionally, if the axillary arch was present, the mean operative time of SLNB was 20.8 minutes, compared to 12.5 minutes when the axillary arch was not present (p<0.001). If the axillary arch was present, the SLN was often located in a high axillary region (67%) rather than in a general low axillary location.
The axillary arch was found to be a significant factor affecting intraoperative SLN failure rate. It is necessary to keep in mind that carefully checking the high axillar region during SLNB in breast cancer patients with the axillary arch is important for reducing SLN sampling failure.
PMCID: PMC4197354  PMID: 25320622
Axillary arch; Breast neoplasms; Sentinel lymph node biopsy
13.  Breast Cancer Screening Knowledge and Perceived Health Beliefs among Immigrant Women in Korea 
Journal of Breast Cancer  2014;17(3):279-286.
Recently, through international marriage, immigrant women have rapidly increased throughout Korea. This study was performed to identify health beliefs and practices related to breast cancer screening in immigrant women in Korea.
A cross-sectional survey was carried out between March and July 2012, and study population included immigrant females from six other Asian countries (Cambodia, China, Japan, Mongolia, Vietnam, and the Philippines). We surveyed 197 women and categorized them into four groups according to home countries. The questionnaire consisted of 55 items, including demographic and socioeconomic factors, breast cancer-related knowledge regarding risk factors and symptoms, beliefs and attitudes towards health and breast cancer, perceived susceptibility, barriers, and benefits of screening.
Japanese participants were significantly older and had resided in Korea for more years than other country-of-origin groups (all p<0.001), and showed higher screening rates without statistical significance (p=0.392). In multivariate analysis, country of origin showed a significant correlation with knowledge (p=0.001), positive beliefs (p=0.002), and perceived benefits (p=0.025) of breast cancer screening. The group with the lowest household income showed a significantly lower score of perceived benefits (p=0.022). Through analysis to identify factors affecting participation in screening mammography, we found that education level (p=0.009), occupation status (p=0.006), and Korean language fluency (p=0.002) were independent predictors for screening behavior.
This study identified conditions related to breast cancer screening knowledge, perception, and behavior of immigrant women in Korea. The results reflect the need for increased social aids to remove barriers to medical services and more educational programs to facilitate higher rates of screening.
PMCID: PMC4197359  PMID: 25320627
Breast neoplasms; Emigrants and immigrants; Health behavior; Health knowledge; Mass screening
14.  Role of secreted type I collagen derived from stromal cells in two breast cancer cell lines 
Oncology Letters  2014;8(2):507-512.
Collagen is one of numerous components of the cellular microenvironment. To date, the association between the microenvironment and tumorigenesis of malignant breast cancer remains elusive. Therefore, the aim of the present study was to investigate the potential role of a secretory protein of stromal cells, type I collagen, in the development of the aggressive characteristics of breast cancer cells. MDA-MB231 and MCF7 breast cancer cell lines were maintained in cultured media of normal human dermal fibroblasts (HDFs) and type I collagen-containing media. The morphological changes, adhesion capacity and matrix metalloproteinase (MMP)-1, -2 and -9 mRNA levels were evaluated. The results revealed that cell sprouting and adhesion capacity were enhanced in the MCF7 and MDA-MB231 breast cancer cells in HDF-conditioned culture media as well as in response to type I collagen treatment. The expression of MMP-9 mRNA was high in breast cancer cells cultured with the media of normal HDFs, compared with that of the control media. These data indicate that type I collagen, which is secreted by stromal fibroblasts, may augment the aggressive characteristics of breast cancer cells through the induction of MMP-9 mRNA.
PMCID: PMC4081378  PMID: 25013462
breast cancer; collagen type I; fibroblast; neoplasm; matrix metalloproteinases
15.  Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR) 
BMC Cancer  2014;14:170.
Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.
Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively.
This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.
Trial registration Identifier NCT01589367
PMCID: PMC3984742  PMID: 24612502
Metformin; Letrozole; Neoadjuvant; Estrogen receptor-positive Breast cancer
16.  Polyostotic Fibrous Dysplasia Mimicking Multiple Bone Metastases in a Patient with Ductal Carcinoma In Situ 
Journal of Breast Cancer  2014;17(1):83-87.
Whole-body bone scans and whole body 18F-fluorodeoxyglucose positron emission tomographic/computed tomographic scans are sensitive for detecting bone metastasis in patients with breast cancer. However, it is often difficult to discriminate between bone metastasis and other nonmalignant bone lesions. Polyostotic fibrous dysplasia is a rare disorder characterized by the osteoid medullary cavity filling with fibrous tissue causing bony expansion. We report the case of a 42-year-old female patient with ductal carcinoma in situ, which appeared to have multiple bone metastases on initial work-up images. Subsequently, the bone metastases were identified as polyostotic fibrous dysplasia. The patient underwent modified radical mastectomy and subsequently visited for a second opinion regarding the bony metastases. She underwent right ilium computed tomography-guided biopsy. Pathology was consistent with fibrous dysplasia. This patient received only adjuvant tamoxifen, and 1.5 years later, there was no evidence of recurrence.
PMCID: PMC3988348  PMID: 24744802
Breast neoplasms; Fibrous dysplasia of bone; Neoplasm metastasis; Positron-emission tomography; Whole body imaging
17.  Comparison of acute skin reaction following morning versus late afternoon radiotherapy in patients with breast cancer who have undergone curative surgical resection 
Journal of Radiation Research  2014;55(3):553-558.
We investigated the relationship between the time of radiotherapy (RT) and treatment outcomes in breast cancer. Patients with pathologic T1–2N0–1 breast cancer who received adjuvant RT in the morning (before 10:00 AM) or late afternoon (after 3:00 PM) were eligible for inclusion in this study. We retrospectively compared the clinicopathologic characteristics, acute skin reaction, and survival outcomes according to the time of RT. The median follow-up duration was 83 months (range, 10–131 months). From the 395 eligible patients, 190 (48.1%) and 205 (51.9%) patients were classified into the morning RT group and the afternoon RT group, respectively. The clinicopathologic characteristics were relatively well balanced between the treatment groups, except for pathologic N-stage (P = 0.0409). Grade 2 or higher acute skin reaction according to the Radiation Therapy Oncology Group criteria was observed in 39 (9.9%) patients, with a higher frequency in the afternoon RT group than the morning RT group (13.7% vs 5.8%, respectively; P = 0.0088). There was no difference in the failure patterns or survival outcomes between the treatment groups. RT in late afternoon was associated with increased Grade 2 or more skin reaction after RT for breast cancer patients, but treatment outcomes did not differ according to the time of RT. Individualized considerations for treatment should be taken into account to reduce the risk of skin reactions.
PMCID: PMC4014164  PMID: 24385471
circadian rhythm; radiotherapy; radiation-induced dermatitis; breast cancer
18.  Comparison of the Characteristics of Medullary Breast Carcinoma and Invasive Ductal Carcinoma 
Journal of Breast Cancer  2013;16(4):417-425.
Medullary breast carcinomas (MBC) have been known to represent a rare breast cancer subtype associated with a more favorable prognosis than invasive ductal carcinomas (IDC). The purpose of this study was to compare the clinicopathologic characteristics and outcomes of MBC with those of IDC.
We retrospectively reviewed medical records of patients with invasive breast cancer who were managed surgically from August 1995 to June 2010.
Fifty-two patients were identified with MBC and 5,716 patients were identified with IDC. The clinicopathologic features, disease-free survival (DFS), and overall survival (OS) of patients with MBC were compared with those of patients with IDC. The MBC group presented at a younger age (p=0.005) and had a significant association with a higher histological grade (p=0.003) and nuclear grade (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node metastasis was rare (p<0.001). The DFS and OS did not differ significantly between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4% vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS and OS were nuclear grade, histological grade, tumor size, lymph node metastasis, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS and OS were not significantly different between IDC and MBC according to histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12-6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77, p=0.692).
Although MBC has specific clinicopathologic features, its prognosis does not differ from IDC and is determined by prognostic factors such as tumor size and lymph node metastasis. Therefore, patients with MBC also require the same intensive treatment provided for IDC.
PMCID: PMC3893344  PMID: 24454464
Breast neoplasms; Lymphatic metastasis; Medullary carcinoma; Prognosis
19.  Prognostic factors for survivals from first relapse in breast cancer patients: analysis of deceased patients 
Radiation Oncology Journal  2013;31(4):222-227.
This study was performed to evaluate prognostic factors for survival from first relapse (SFFR) in stage I-III breast cancer patients.
Materials and Methods
From June 1994 to June 2008, 3,835 patients were treated with surgery plus postoperative radiotherapy and adjuvant chemotherapy for stage I-III breast cancer at Samsung Medical Center. Among them, a total of 224 patients died by June 2009, and 175 deaths were of breast cancer. Retrospective review was performed on medical records of 165 patients who met the inclusion criteria of this study. Univariate and multivariate analysis were done on survivals according to variables, such as age, stage, hormone status of tumor, disease-free interval (DFI), sites of first failure, number of organs involved by recurrent disease (NOR), application of salvage treatments, and existence of brain or liver metastasis (visceral metastasis).
Patients' median overall survival time was 38 months (range, 8 to 123 months). Median SFFR was 17 months (range, 5 to 87 months). Ninety percent of deaths occurred within 40 months after first recurrence. The patients with SFFR ≤1 year had tendency of triple-negativity, shorter DFI (≤2 years), larger NOR (>3), visceral metastasis for first relapse than the patients with SFFR >1 year. In multivariate analysis, longer DFI (>2 vs. ≤2 years), absence of visceral metastasis, and application of salvage treatments were statistically significant prognosticators for longer SFFR.
The DFI, application of salvage treatments, and visceral metastasis were significant prognostic factors for SFFR in breast cancer patients.
PMCID: PMC3912236  PMID: 24501710
Survival; Recurrence; Prognosis; Breast neoplasms
20.  Association between BRCA Mutation Status, Pathological Findings, and Magnetic Resonance Imaging Features in Patients with Breast Cancer at Risk for the Mutation 
Journal of Breast Cancer  2013;16(3):308-314.
We investigated the relationship between BRCA mutations, pathological findings, and magnetic resonance imaging (MRI) features in patients with breast cancer at risk for the mutation.
Genetic testing for BRCA mutations was performed in 275 breast cancer patients with at least one risk factor for the mutation. Using the breast imaging reporting and data system MR lexicon, morphological and kinetic features were reviewed on MRI scans of 230 tumors in 209 patients. The relationship between BRCA mutations, pathologic findings, and MRI data was examined, and disease recurrence was estimated.
BRCA mutations were detected in 48 patients (23.0%), of which 21 (10.0%) were in BRCA1, and 25 (12.0%) in BRCA2. Additionally, two patients (1.0%) had mutations in both genes. Cancers in patients with BRCA1 mutations more frequently showed a higher nuclear grade (p=0.0041), and triple-negative (TN) phenotype (p<0.0001). On MRI scans, the cancers were seen as mass-type in 182 out of 230 lesions (79.1%), and nonmass type in 48 cases (20.9%). Among the features indentified by MRI, rim enhancement was significantly associated with molecular subtypes based on immunohistochemistry (p<0.0001), and nuclear grade (p=0.0387) in multiple logistic regression analysis. Rim enhancement on MRI, along with advanced pathologic N stage, was associated with increased disease recurrence (p=0.0023) based on multivariate analysis. However, the proportion of mass and nonmass tumors, and the distribution of morphological shape, margin, internal enhancement, and kinetic features assessed by MRI were not different according to BRCA mutation status.
BRCA1 mutations were associated with aggressive pathological characteristics, and the TN phenotype. Rim enhancement was frequently seen on MRI scans of high-grade cancers and in the TN phenotype. And it was a significant predictor of disease recurrence. However, a direct association with BRCA mutations was not observed.
PMCID: PMC3800727  PMID: 24155760
BRCA1 genes; Breast neoplasms; Magnetic resonance imaging; Recurrence
21.  Breast Metastasis from Rhabdomyosarcoma of the Anus in an Adolescent Female 
Journal of Breast Cancer  2013;16(3):345-348.
Rhabdomyosarcoma (RMS) of the breast is rare and there is scant information about the clinical behavior and treatment strategies. We report an adolescent female patient with metastatic RMS of the breast from the anus. An 18-year-old female patient was referred to our clinic due to palpable mass in the left breast. At age seven, she was diagnosed with acute lymphoblastic leukemia and treated with chemoradiation therapy. After 10 years of complete remission state, she presented with anal mass which was diagnosed as RMS and she received chemoradiation therapy. After 1 year of complete remission state, she noticed a palpable mass in her left breast. The breast mass was diagnosed as metastatic RMS based on core needle biopsy specimen. The RMS in breast was excised for the decreasing tumor burden despite of another metastatic lesion. Although rarely reported, metastasis of RMS should be considered as a cause of breast mass. Tissue biopsy is recommended when clinically suspected lesion is detected.
PMCID: PMC3800733  PMID: 24155766
Adolescent; Anus; Breast; Neoplasm metastasis; Rhabdomyosarcoma
22.  Experience of treatment of patients with granulomatous lobular mastitis 
To present the author's experience with various treatment methods of granulomatous lobular mastitis (GLM) and to determine effective treatment methods of GLM.
Fifty patients who were diagnosed with GLM were classified into five groups based on the initial treatment methods they underwent, which included observation (n = 8), antibiotics (n = 3), steroid (n = 13), drainage (n = 14), and surgical excision (n = 12). The treatment processes in each group were examined and their clinical characteristics, treatment processes, and results were analyzed respectively.
Success rates with each initial treatment were observation, 87.5%; antibiotics, 33.3%; steroids, 30.8%; drainage, 28.6%; and surgical excision, 91.7%. In most cases of observation, the lesions were small and the symptoms were mild. A total of 23 patients underwent surgical excision during treatment. Surgical excision showed particularly fast recovery, high success rate (90.3%) and low recurrence rate (8.7%).
The clinical course of GLM is complex and the outcome of each treatment type are variable. Surgery may play an important role when a lesion is determined to be mass-forming or appears localized as an abscess pocket during breast examination or imaging study.
PMCID: PMC3699681  PMID: 23833753
Breast; Granulomatous mastitis; Treatment; Excision
23.  The Role of the CDH1 Promoter Hypermethylation in the Axillary Lymph Node Metastasis and Prognosis 
Journal of Breast Cancer  2013;16(1):16-22.
Hypermethylation of the tumor suppressor genes is frequently observed in the tumor development and progression. However, the correlation between the hypermethylation of the tumor suppressor genes, CDH1 and the axillary lymph node (ALN) metastasis is not fully elucidated. To verify the role of the CDH1 promoter hypermethylation in the ALN metastasis and prognosis, we compared the methylation status of the CDH1 genes in the primary lesion and the paired metastatic ALNs.
We selected a total of 122 paraffin-embedded specimens of the primary and paired metastatic lymph node from 61 breast cancer patients and analyzed the frequency of hypermethylation in the primary and metastatic lymph node using the methylation-specific polymerase chain reaction. In addition, the methylation status of CDH1 was analyzed with the clinicopathologic characteristics, the disease-free survival and disease-specific survival.
The hypermethylation of CDH1 gene was identified in 54 (88.5%) of the 61 patients who had axillary metastasis. The hypermethylation status of the CDH1 gene was significantly increased in the metastatic ALNs compared with that in the primary tumors (60.7% vs. 45.9%, p<0.001). The hypermethylation status of the CDH1 genes in the metastatic ALNs was associated with a poor histologic grade (p=0.041) and the patients who had methylated tumor in the primary lesion showed worse disease-free survival than the patients who did not have methylated tumor (p=0.046).
This study suggests that hypermethylation of the CDH1 gene may play a pivotal role in the metastasis of the axillary lymph node and the breast cancer recurrence.
PMCID: PMC3625765  PMID: 23593077
Breast neoplasms; Lymph nodes; Methylation; Recurrence; Tumor suppressor genes
24.  Validation of a Web-Based Tool to Predict the Ipsilateral Breast Tumor Recurrence (IBTR! 2.0) after Breast-Conserving Therapy for Korean Patients 
Journal of Breast Cancer  2013;16(1):97-103.
IBTR! 2.0 is a web-based nomogram that predicts the 10-year ipsilateral breast tumor recurrence (IBTR) rate after breast-conserving therapy. We validated this nomogram in Korean patients.
The nomogram was tested for 520 Korean patients, who underwent breast-conserving surgery followed by radiation therapy. Predicted and observed 10-year outcomes were compared for the entire cohort and for each group, predefined by nomogram-predicted risks: group 1, <3%; group 2, 3% to 5%; group 3, 5% to 10%; group 4, >10%.
In overall patients, the overall 10 year predicted and observed estimates of IBTR were 5.22% and 5.70% (p=0.68). In group 1, (n=124), the predicted and observed estimates were 2.25% and 1.80% (p=0.73), in group 2 (n=177), 3.95% and 3.90% (p=0.97), in group 3 (n=181), 7.14% and 8.80% (p=0.42), and in group 4 (n=38), 11.66% and 14.90% (p=0.73), respectively.
In a previous validation of this nomogram based on American patients, nomogram-predicted IBTR rates were overestimated in the high-risk subgroup. However, our results based on Korean patients showed that the observed IBTR was higher than the predicted estimates in groups 3 and 4. This difference may arise from ethnic differences, as well as from the methods used to detect IBTR and the healthcare environment. IBTR! 2.0 may be considered as an acceptable nomogram in Korean patients with low- to moderate-risk of in-breast recurrence. Before widespread use of this nomogram, the IBTR! 2.0 needs a larger validation study and continuous modification.
PMCID: PMC3625777  PMID: 23593089
Breast neoplasms; Nomograms; Radiotherapy; Recurrence; Validation studies
25.  Methylation and Immunoexpression of p16INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16INK4a Hypermethylation in Plasma by Real-Time PCR 
Korean Journal of Pathology  2012;46(6):554-561.
The p16INK4a gene methylation has been reported to be a major tumorigenic mechanism.
We evaluated the methylation status of the p16INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay.
The frequencies of p16INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16INK4a was significantly higher in the cancer patients than the normal controls (p<0.001).
High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.
PMCID: PMC3540333  PMID: 23323106
Breast; Neoplasms; p16; Methylation; Immunohistochemistry

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