PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. 18Fluorodeoxyglucose-positron emission tomography (18F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both 18F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both 18F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.
Breast Neoplasms* ; Cohort Studies ; Drug Therapy* ; Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes ; Neoadjuvant Therapy ; Predictive Value of Tests ; Prospective Studies* ; Sentinel Lymph Node Biopsy* ; Ultrasonography

PURPOSE: Liver resection with colorectal liver metastasis widely accepted and has been considered safe and effective therapeutic option. However, the role of liver resection in breast cancer with liver metastasis is still controversial. Therefore, we reviewed the outcome of liver resection in breast cancer patients with liver metastases in a single hospital experiences. MATERIALS AND METHODS: Between January 1991 and December 2006, 2176 patients underwent breast cancer surgery in Gangnam Severance Hospital. Among these patients, 110 cases of liver metastases were observed during follow-up and 13 of these patients received liver resection with potential feasibility to achieve an R0 resection. RESULTS: The median time interval between initial breast cancer and detection of liver metastasis was 62.5 months (range, 13-121 months). The 1-year and 3-year overall survival rates of the 13 patients with liver resection were 83.1% and 49.2%, respectively. The 1-year and 3-year overall survival rates of patients without extrahepatic metastasis were 83.3% and 66.7% and those of patients with extrahepatic metastasis were 80.0% and 0.0%, respectively (p=0.001). CONCLUSION: Liver resection for metastatic breast cancer results in improved patient survival, particularly in patients with solitary liver metastasis and good general condition.
Adult ; Breast Neoplasms/*complications/mortality/*surgery ; Female ; Humans ; Liver Neoplasms/mortality/*secondary/*surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate

PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology ; *Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Republic of Korea ; Survival Analysis ; Survival Rate ; Time Factors

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Adult ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy/genetics/*secondary ; Breast Neoplasms/drug therapy/genetics/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Regression Analysis ; Retrospective Studies ; Survival Analysis

PURPOSE: Some recent trials suggest that postoperative adjuvant radiotherapy (RT) may be safely omitted after breast-conserving surgery (BCS) for some patients with ductal carcinoma in situ (DCIS). In this study, we reviewed clinical outcomes of patients with DCIS treated with partial mastectomy (PM) without adjuvant RT. MATERIALS AND METHODS: Medical records of 28 patients (29 breasts) with DCIS who were treated with PM, but without RT, between April 1991 and December 2010 were retrospectively analyzed. Based on established criteria (2.0 cm or less in size and no comedonecrosis), 18 patients were treated without RT after PM. Seven patients (8 breasts) who did not receive RT due to refusal were also included in this study. Three other patients were excluded because data concerning comedonecrosis were not available. RESULTS: For the 25 patients included in this study, the mean age of the 18 patients who met the criteria was 47.9+/-6.2 years, and 47.6+/-12.7 years for the 7 patients who did not. The mean sizes of the primary tumors were 0.6+/-0.4 cm and 0.9+/-0.3 cm, respectively, in these two groups. Among these 25 patients (26 breasts) treated without RT, we observed no ipsilateral breast tumor recurrence or mortality within a mean follow-up of 84 months. CONCLUSION: Based on this small number of cases, patients with DCIS, who were selected for tumor size less than 2 cm and absence of comedonecrosis, may be treated successfully with BCS; adjuvant RT may be omitted.
Adult ; Breast Neoplasms/*radiotherapy/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*radiotherapy/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; *Radiotherapy, Adjuvant ; Retrospective Studies ; Treatment Outcome

Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer.
Animals ; Apoptosis/drug effects ; Bone Density Conservation Agents/pharmacology ; Bone Neoplasms/prevention & control/*secondary ; Bone and Bones/drug effects/pathology ; Breast Neoplasms/*drug therapy/*pathology ; Diphosphonates/*pharmacology ; Female ; Humans ; Imidazoles/*pharmacology ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays

PURPOSE: An in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was designed to require only a limited number of cells and shorten test turnaround time with a high success rate. This study investigated the correlation between in vitro doxorubicin sensitivity of tumor cells and early systemic recurrence, defined as recurrence within 2 years after surgery. METHODS: From January 2004 to March 2007, the ATP-CRA for doxorubicin was tested in 128 patients among breast cancer patients treated at Gangnam Severance Hospital, Seoul, Korea. The American Joint Committee on Cancer stages for all patients were II and III. All patients received doxorubicin-based chemotherapy. Selected patients were divided into a chemosensitive group and a non-chemosensitive group, according to a 40% cell death rate as a cut-off value. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with breast cancer. RESULTS: The mean age of the patients investigated was 44.6-years-old, the mean follow-up period was 39.9 months, and recurrence free survival was 38.6 months. Thirteen recurrences were observed during follow-up. Among 13 patients with a recurrence, eight had a recurrence within 2 years (early recurrence). All of the early recurring patients belonged to the non-sensitive group. Doxorubicin sensitivity results measured by ATP-CRA were related with early recurrence free survival in patients with breast cancer (p=0.030). The mean cell death rate derived from the ATP-CRA for the early recurrence group tended to be lower than that of the non-early recurrence group, but the difference was not statistically significant (p=0.05). CONCLUSION: Doxorubicin sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence against doxorubicin-based adjuvant chemotherapy in patients with breast cancer.
Mortality ; Breast Neoplasms

PURPOSE: Few studies have reported ovarian cancer risks in Korean patients with the BRCA1/2 mutation. We investigated the prevalence of ovarian cancer in Korean women at high risk for hereditary breast-ovarian cancer (HBOC) syndrome and reviewed the clinicopathological factors of ovarian cancer. METHODS: Female subjects who were enrolled in the Korean Hereditary Breast Cancer study were included. The questionnaire included a personal and family history of cancer. The BRCA1/2 mutation and CA-125 level were tested at the time of enrollment. A transvaginal ultrasonogram (TVUS) was recommended for subjects with an elevated CA-125 level. RESULTS: A total of 1,689 patients were included. No ovarian cancer was newly diagnosed by CA-125 level or TVUS during the enrollment. The prevalence of ovarian cancer was 1.71% in BRCA1/2 mutation carriers and 0.39% in non-carriers. Among 11 patients with ovarian cancer, five had the BRCA1 mutation and one had the BRCA2 mutation. The most common histopathological type was serous cystadenocarcinoma. No difference in clinicopathological findings between BRCA1/2 mutation carriers and non-carriers was observed. CONCLUSION: The prevalence of ovarian cancer was 58-fold elevated in women at high-risk for HBOC syndrome and 146-fold elevated in the BRCA1 subgroup, compared with the Korean general population. Further investigation with a long-term follow-up is required to evaluate BRCA1/2 gene penetrance.
Female ; Humans ; Breast Neoplasms ; Ovarian Neoplasms

PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.
Adenosine Triphosphate ; Breast ; Breast Neoplasms ; Cell Death ; Deoxycytidine ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Paclitaxel ; Polyphosphates ; Taxoids ; Vinblastine

PURPOSE: The purpose of this study was to identify biopsychosocial predictors of the quality of life in breast cancer patients. Disease factors (disease stage, type of surgery, type of treatment, family history), personal factors (age, education level, income), and psychosocial factors (psychological symptoms, optimism, self-esteem, husband's support, cancer coping) were included in biopsychosocial predictors. METHODS: A total of 128 breast cancer patients were recruited. Subjects were assessed by the Optimism Scale, the Selfesteem Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23), the Symptom Checklist-90-Revision (SCL-90-R), and the Korean Cancer Coping Questionnaire (KCCQ). RESULTS: Disease factors and personal factors were not different between the high and low quality of life group. But the psychosocial factors were significantly different. Somatization, anxiety, depression, interpersonal sensitivity, hostility, and phobic anxiety showed significantly lower scores in the high quality of life group than the low group. Optimism, self-esteem and husband's support showed significantly higher score in the high quality of life group than the low group. In a stepwise multiple regression analysis, not disease factors and personal factors but the psychosocial factors significantly predicted the quality of life in breast cancer patients. Especially, somatization and depression significantly predicted the quality of life. CONCLUSION: Among psychosocial factors, somatization and depression were the most significant predictors of the quality of life in breast cancer patients. These results supported psychosocial intervention should be needed to breast cancer patients, in order to improve the quality of life.
Anxiety ; Breast ; Breast Neoplasms ; Depression ; Hostility ; Humans ; Quality of Life ; Somatoform Disorders ; Surveys and Questionnaires