Prevalence of BRCA1 and BRCA2 Mutations in Korean Breast Cancer Patients

The incidence of breast cancer in Korea has been increasing in recent years, such that it is now the most common female cancer. Breast cancer in Korea is characterized by an earlier age of onset than in Western countries, suggesting that it would be related with genetic background. We assayed germline mutations in the BRCA genes to evaluate their genetic pathology in Korean breast cancer patients. The study subjects consisted of 173 patients at clinically higher risk and 109 unselected patients. Germline mutations in the entire coding sequences of the BRCA1 and BRCA2 genes were analyzed by Conformation-Sensitive Gel Electrophoresis (CSGE), and any aberrantly-sized band was sequenced. BRCA mutations were present in 12.7% of the high risk patients, compared with 2.8% of the unselected patients. Among high risk patients, mutations were most prevalent in patients with a family history of breast or first-degree ovarian cancer (22.1%), followed by those with male breast cancer (20%), bilateral breast cancer (20%), multiple organ cancer including breast (13%) and younger breast cancer patients (aged<35 yr) (8.1%). Moreover, BRCA mutations were detected in 34.8% of patients having two highrisk factors. These findings suggest that BRCA gene mutation analysis should be performed on Korean patients with high-risk factors for breast cancer.

Experience of Photodynamic Therapy for Palliation of the Chest Wall and Skin Recurrence in a Patient with Breast Cancer

In patient treated by mastectomy for breast cancer, chest wall and skin recurrences are frequently encountered. Chest wall recurrence results in profound physical and psychological morbidity, and often heralds the appearance of other, more life threatening metastasis. Traditionally the two most common treatments have been site-specific radiation and resection. Photodynamic therapy (PDT) provided an alternative treatment modality using a photosensitizer and laser light to induce selective tumor necrosis. The patient was 64- years old female, had undergone breast conserving surgery for cancer of the right breast. Chest wall and skin metastasis recurred at 40 months after the adjuvant treatment of chemotherapy. The lesions were progressed despite 2nd, 3rd chemotherapy and hyperthermal therapy. The light was administered through a diode laser turned to 630 nm wave length (150 J/cm2 in light dosage, 200 mW/cm2 in intensity), 72 h after photosensitizing agent injection. There was clinical evidence of partial response, defined as granulation tissue with re-epitheliaization from the periphery of normal epithelium. PDT has demonstrated good results in other solid tumors at some hospitals, however there has been no application for breast cancer in Korea previously. Our experience suggests that PDT is non-invasive procedure that is highly tolerable, particularly when compared with other modalities, and an effective treatment method for chest wall or skin recurrence that shows no response to other treatments.

Immediate Breast Reconstruction Following Mastectomy for the Treatment of Advanced Breast Cancer Patients

PURPOSE: To elucidate whether there is a delay of adjuvant treatment or detection of recurrences, or an increasing of the recurrence of tumorsin clinically advanced breast cancer patients. METHODS: The study group included 55 patients underwent mastectomy with immediate reconstruction (IBR), and 563 patients who received the mastectomy without reconstruction (non-IBR), and who were stage IIB and IIIA breast cancer patients, at Asan Medical Center between Jun 1993 and December 2000. We retrospectively assessed the comparative outcomes through using follow-up data. RESULTS: Out of 2,057 patients who had undergone the mastectomy on during the period, 175 (8.5%) underwent immediate reconstruction. 55 of them (31.6%) were stage IIB and IIIA patients, a similar portion (29.9%) was seen in the 563 patients of same stages without reconstruction. The mean ages of these groups were 37.1 and 46.9 years, that is, the reconstruction group was about 10 years younger. All these patients voluntarily underwent immediate reconstruction. For the patients who were followed up, the local recurrence was 3.6% (2/55) for the IBR group and 5.2% (29/563) for the non-IBR group. On the other hand, the distant relapse rates were 12.7% and 13.9%. The administration of adjuvant chemotherapy was not delayed and radiotherapy was used as an adjuvant treatment after reconstruction in nine of the cases (16.4%). Chemotherapy was also conducted in 98.2% of the IBR group and 77.3% of the non-IBR group. While radiotherapy was used in the IBR group less frequently, there was no statistical difference between the two groups (P=0.63). CONCLUSION: Immediate reconstruction following mastectomy for the treatment of breast cancer is now more frequently performed. IBR can be done in clinically advanced breast cancer without increasing the risk of treatment failure or modification.

The Reliability of Histoculture Drug Response Assay (HDRA) in Chemosensitivity Tests for Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Cancers are highly individual in their response to chemotherapy, however attempts to predict tumor response to drugs using in vitro cell culture have largely failed. A new technology, the histoculture drug response assay (HDRA), appears to have solved many previous problems. The purpose of this study is to evaluate the reliability of HDRA in a chemosensitivity test for breast cancer. MATERIALS AND METHODS: Tumor specimens from breast cancer patients were evaluated by HDRA using different chemotherapeutic agents. Each specimen was tested using a blind method in order to determine the reproducibility of HDRA results for the same tissue and with a triplicated assay in order to determine reproducibility by different examiners. The evaluative power of this assay and the chemosensitivity of drugs for each specimen was determined. RESULTS: Specimens of 92.9% (65/70) were successfully cultured and evaluated for chemosensitivity. The reproducibility of HDRA for the same tissue was 75% (100% agreement) and 100% (over 70% agreement), respectively. And the reproducibility by different examiners was 78.9% (100% agreement) and 94.7% (over 70% agreement), respectively. Each specimen demonstrated a response to at least one agent. CONCLUSION: The evaluative power and reproducibility of HDRA were high, therefore it might serve as a reliable clinical method for chemosensitivity testing. However, there is a need for clinical trial in which patients are initially randomized for treatment either by HDRA direction or by clinician's choice.

Assessment of MIB1 (Ki-67) Labeling Index and Correlation with Other Well Established Prognostic Factors in Breast Cancer

PURPOSE: The MIB1 labeling index is new method utilizing a monoclonal antibody against Ki-67 antigen and useful for evaluating the proliferation rate in breast cancer due to its ease of use and reliability. We compared the MIB1 labeling index to other, well established prognostic factors and assessed the prognostic value of MIB1 in 564 breast cancers. METHODS: The MIB1 (Ki-67 equivalent monoclonal antibody) proliferation rate, MIB1 labeling index, was determined in formalin-fixed, paraffin-embedded tissue specimens of 564 primary breast cancer patients who underwent surgery between March 1998 and February 2000 at Seoul National University Hospital. The clinicopathologic characteristics of the primary tumor such as age, tumor size, histologic type, nuclear grade, histologic grade, hormone receptor status and various tumor markers (p53, c-erbB-2, bcl-2) were compared with the value of the MIB1 labeling Index. RESULTS: The mean value of MIB1 labeling index was 6.9. MIB1 labeling index was correlated to younger age (p= 0.011), histologic types, low nuclear grade (p=0.0001), high histologic grade (p=0.0001), p53 positive (IDC) (p=0.0001), c-erbB-2 positive (DCIS) (p=0.01), comedo type (DCIS) (p= 0.001) and inversely correlated to hormone receptor positivity (p=0.0001), bcl-2 positive (IDC) (p=0.001). No correlation was found in tumor size, lymph node status and c-erbB-2 positive (IDC). CONCLUSION: The MIB1 labeling index correlated well with well-established poor prognostic factors. The MIB1 labeling index may be an important prognostic determinant in breast cancer.

Sentinel Node Biopsy in Breast Cancer Using a Gamma-detection Probe

PURPOSE: Sentinel lymph node (SLN) biopsy has emerged as a substitute for a conventional axillary lymph node (ALN) dissection in early breast carcinomas. We evaluated SLN biopsy in breast carcinoma using a gamma-detection probe in order to identify its accuracy as a staging procedure for lymph node status. METHODS: Fifty-one patients with breast carcinomas who underwent a SLN biopsy followed by an ALN dissection between June 1999 and January 2001 were evaluated. Tc 99m antimony trisulfide colloid was used as a tracer and SLN biopsy using a gamma-detection probe was done following breast lymphoscintigraphy. Intraoperative imprint cytology (II C) was done for each SLN. If a SLN biopsy was free of metastasis by permanent hematoxylin and eosin (H&E) staining, immun ohistochemical (IHC) staining using pan-cytokeratin was do ne to detect micrometastasis. RESULTS: ALN metastases were identified in 21.6% of pa tients and the resection rate of SLN was 94.1%. The mean number of resected SLN was 1.8, all located at the axilla. IIC had a sensitivity of 72.7% and a spe cificity of 100%. The false-negative rate of SLN biopsy was 12.5% when SLNs were evaluated by H&E staining alone. However, the false-negative rate improved up to 0% when IHC staining was added. CONCLUSION: SLN biopsy using a gamma-detection probe proved to be a very sensitive method to detect SLN in breast carcinoma patients. Frozen biopsy should be added to im prove the outcomes of intraoperative examination of SLN. If permanent biopsy revealed that SLN was free of tumorthe by H&E staining, IHC staining should be done to improve false-negative rate of SLN biopsy.

Sentinel Node Biopsy in Breast Cancer Using a Gamma-detection Probe

PURPOSE: Sentinel lymph node (SLN) biopsy has emerged as a substitute for a conventional axillary lymph node (ALN) dissection in early breast carcinomas. We evaluated SLN biopsy in breast carcinoma using a gamma-detection probe in order to identify its accuracy as a staging procedure for lymph node status. METHODS: Fifty-one patients with breast carcinomas who underwent a SLN biopsy followed by an ALN dissection between June 1999 and January 2001 were evaluated. Tc 99m antimony trisulfide colloid was used as a tracer and SLN biopsy using a gamma-detection probe was done following breast lymphoscintigraphy. Intraoperative imprint cytology (II C) was done for each SLN. If a SLN biopsy was free of metastasis by permanent hematoxylin and eosin (H&E) staining, immun ohistochemical (IHC) staining using pan-cytokeratin was do ne to detect micrometastasis. RESULTS: ALN metastases were identified in 21.6% of pa tients and the resection rate of SLN was 94.1%. The mean number of resected SLN was 1.8, all located at the axilla. IIC had a sensitivity of 72.7% and a spe cificity of 100%. The false-negative rate of SLN biopsy was 12.5% when SLNs were evaluated by H&E staining alone. However, the false-negative rate improved up to 0% when IHC staining was added. CONCLUSION: SLN biopsy using a gamma-detection probe proved to be a very sensitive method to detect SLN in breast carcinoma patients. Frozen biopsy should be added to im prove the outcomes of intraoperative examination of SLN. If permanent biopsy revealed that SLN was free of tumorthe by H&E staining, IHC staining should be done to improve false-negative rate of SLN biopsy.