Frequency of the CHEK2 1100delC Mutation in Korean Women with Early Onset Breast Cancer / 한국유방암학회지

PURPOSE: Sequence variants in the cell cycle checkpoint kinase 2 (CHEK2 1100delC) are associated with an increased risk for breast cancer in women carrying this mutation. It is a lowpenetrance breast cancer susceptibility allele, frequently observed in patients with a family history of breast cancer and/or young age, with the frequency varying according to race or ethnicity. In this study, we evaluated the significance of CHEK2 1100delC in predisposition to breast cancer by assessing its frequency in material from 101 Korean women patients with early-onset breast cancer. METHODS: One hundred and one Korean patients with earlyonset breast cancer (40 yr old or younger) were selected for this study. All the patients had been screened for BRCA1 and BRCA2 mutations and 14 patients had deleterious mutations. Of the 101 patients entered for this study, 14 had family history of breast cancer and 7 had bilateral breast cancers. Mutation detection of CHEK2 1100delC was based on analysis of primer extension products generated from previously-amplified genomic DNA using a chip based MALDI-TOP mass spectrometry platform (Sequenom, Inc., San Diego, CA, USA). RESULTS: None of the 101 Korean patients with a family history of breast cancer and early-onset breast cancer who were candidates for the BRCA1 and BRCA2 test carried the 1100 delC mutation, which is observed in Caucasians with limited frequency. CONCLUSION: We previously observed higher or comparable prevalence of BRCA1 and BRCA2 mutations in Korean patients with breast cancer compared to Caucasians. However, the CHEK2 1100delC mutation is absent or infrequent in Korean patients with breast cancer who have a high risk of BRCA1 and BRCA2 mutations, making its screening irrelevant.

A Comparative Study of Cyclooxygenase-2 Expression in Korean and Caucasian Patients with Early-Onset Breast Cancer / 한국유방암학회지

PURPOSE: Several studies have indicated that there are a number of differences in tumor biolog associated with race or ethnicity. The median age at the time of diagnosis for Korean women with breast cancer is 45 years, and this is approximately 15 years younger than Caucasian patients in the Western countries. We previously reported that was a significant difference found in the expression of HER-2/neu between Korean and Caucasian patients with early-onset breast carcinoma. In this study, we compared cyclooxygenase-2 (COX-2) expression between the two races. METHODS: One hundred and seventy two Korean women who were diagnosed with breast carcinoma at the age of 45 years or younger and 80 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and the tumor size was evenly distributed between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical COX-2 staining. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. RESULTS: The proportion of tumors that stained positive for COX-2 in Korean and Caucasian women with early-onset breast carcinoma were 33.7% and 25%, respectively. The difference was not statistically significant (p = 0.104). Expression of COX-2 was associated with several clinicopathologic parameters, including positive lymph node status, large tumor size and negative estrogen receptor status. CONCLUSION: A significant difference was not found for the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. Further research will be needed to identify the prognostic role for patients with early-onset breast carcinoma.

Comparative Study of Cyclioxygenase-2 Expression and HER-2/neu Amplification in Korean and Caucasian Women with Early-Onset Breast Carcinoma / 대한방사선종양학회지

PURPOSE: The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in Korean patients. MATERIALS AND METHODS: Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. RESULTS: Proportion of the COX-2 expression in total patients was 27.6%. The percentage of tumors that stained positive for COX-2 in Korean and Caucasian women with early-onset breast carcinoma were 37.9% and 20.8%, respectively. The difference was statistically not significant(p=0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (p=0.046). The 5 year disease free survival rate for patients with COX-2 expression was 67.9%, compared to 81.9% of the COX-2 negative patients and the result was statistically not significant. CONCLUSIONS: A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not observed except estrogen receptor negativity. Large scaled further research including adiotherapy factors will be needed to identify COX-2 as a prognostic role in patients with early-onset breast carcinoma.

Is the BRCA Germline Mutation a Prognostic Factor in Korean Patients with Early-onset Breast Carcinomas? / 대한방사선종양학회지

PURPOSE: The purpose of this study was to determine if there were prognostic differences between BRCA related and BRCA non-related Korean patients with early-onset breast carcinomas. MATERIALS AND METHODS: Sixty women who had developed breast cancers before the age of 40, and who were treated at the Soonchunhyang University Hospital, were studied independently of their family histories. The age range was 18 to 40 with a median of 34.5 years. Lymphocyte specimens from peripheral blood were studied for the heterozygous mutations of BRCA1 and BRCA2 using direct sequencing methods. Immunohistochemistry was performed on the paraffin-embedded tissue blocks that were available. RESULTS: Eleven deleterious mutations (18.3%, 6 in BRCA1 and 5 in BRCA2) and 7 missense mutations of unknown significance (11.7%), were found among the 60 patients. More than half of the mutation were novel, and were not reported in the database. Most of the BRCA-associated patients had no history of breast cancer. No treatment related failures were observed in the BRCA carriers, with the exception of one patientthat had experienced a new primary tumor of the contralateral breast. The seven year relapse free survival rate were 50 and 79% in the BRCA carrier and BRCA negative patients, respectively. Although the expression of estrogen and progesterone receptors were less common, and histological features more aggressive, in the BRCA associated tumors, the outcome of the patients with BRCA mutations was not poorer than that of the patients without deleterious mutations. CONCLUSION: Despite the BRCA mutation carriers having adverse prognostic features, the recurrence rate was relatively lower than that in the BRCA non-carrying Korean patients with early-onset breast carcinomas. In addition, although the prevalence of the BRCA mutation in Korean patients was higher than that in white patients, the penetrance of the cancer seemed to be relatively low in Korean women carrying BRCA mutations. A large population based study of the BRCA mutation, with a long-term follow-up of the study patients will be required to confirm these results.

Characteristics of HER-2/neu Oncogene in Korean Women with Early-onset Breast Cancer by Immunohistochemistry and Fluorescence In Situ Hybridization / 한국유방암학회지

PURPOSE: The purpose of this work was to investigate the prognostic significance of of HER-2/neu (HER-2) oncogene protein overexpression in Korean women with early-onset breast cancer by immunohistochemistry. Furthermore, the results of the test were correlated with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). METHODS: HER-2 status in 60 cases of breast cancer diagnosed at the age of 45 years or younger was investigated by a rabbit polyclonal antibody (Dako) and by applying the Hercep Test, and the results were compared with FISH analysis in all Hercep Test 2+ and 3+ specimens (28 cases) and five HER-2/neu negative specimens. RESULTS: FISH revealed that HER-2 was exclusively amplified in cases with Hercep Test 3+ (20/21). Cases with Hercep Test 3+ or FISH positive tumors were significantly associated with estrogen and progesterone receptor negative tumors. No association was found between HER-2 status and axillary node status. In univariate analysis, FISH status was significantly associated with poor prognosis, but Hercep Test status was not a significant prognostic factor. CONCLUSION: The finding of higher positive tumors and poor prognostic factor of Her-2 in Korean women with early- onset breast cancer may have potential implication for local and systemic management of breast cancer. HER-2 test may be useful for selecting systemic chemotherapy in Korean patients with early onset breast cancer. And the specific anti-HER-2 therapy will be helpful to a large proportion of Korean patients who have more tumors with HER-2 overexpression than White patients.