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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.
Purpose: The extracellular domain (ECD) of the HER-2/neu oncoprotein, whose molecular weight is the range from the 95 kD to 105 kD, is shed into the blood from the cell surface via, proteolysis by a metalloprotease. A monoclonal antibody immunoassay has been developed for measuring the circulating concentrations of serum HER-2/neu ECD (following serum HER-2/neu). Serum HER-2/neu has been reported to be correlated with an increased tumor volume in those patients suffering with breast cancer. We measured the serum CA15-3 level, which is a surrogate marker of the tumor burden, we analyzed the correlation of the serum CA15-3 with the serum HER-2/neu and we analyzed the association of both markers with the clinical outcomes. Methods: The sera for the analysis of both HER-2/neu and CA15-3 were obtained from 99 healthy Korean women, 66 primary breast cancer patients and 43 metastatic breast caner patients. The serum HER-2/neu level was measured quantitatively with using an ADVIA CentaurⓇ automated immunoassay analyzer (Bayer Health Care LLC, Diagnostics Division, Tarrytown, USA) and the CA 15-3 level was measured via radioimmunoassay. Results: The serum HER-2/neu level was increased 23 metastatic cancer patients (53%). On the analysis of the correlation of serum HER-2/neu and CA15-3, the correlation coefficient (r) was 0.8072. Thus a positive serum HER-2/neu test in breast cancer patients was highly associated with the CA15-3 level for assessing whether metastasis was present or not. For the relationship between primary breast cancer and metastatic breast cancer, the former was classified as the control group and the latter as the patient group. The results of the ROC (Receiver Operation Characteristic) curve for serum HER-2/neu and CA15-3 showed no statistically significant differences (p=0.176) but the diagnostic efficacy of the serum HER-2/neu test was measured more exactly than that of CA15-3 and CA15-3 a tool for measuring a tumor marker for the diagnosis of whether metastasis was present or not. Conclusions: Serum HER-2/neu is a significant independent predictive prognostic factor for metastatic breast cancer patients. In view of the results we have achieved so far the serum HER-2/neu level in metastatic breast cancer patients may play an important roll as an independent tumor marker.
Purpose: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. Methods: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. Results: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). Conclusion: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.
Purpose: The objective of this study was to evaluate the change in the practice patterns for managing hereditary breast and ovarian cancer (HBOC) among Korean physicians after the Korean Hereditary Breast Cancer (KOHBRA) study. Methods: The first survey was performed from July to August 2007, at the initiation of the KOHBRA study, and the followup survey was conducted from July to December 2009. Members of the Korean Breast Cancer Society were invited to participate in the study by e-mail. The 2009 survey was conducted with a self-administered questionnaire concerning HBOC management and was identical to the previous questionnaire. Results: According to the 2009 survey, most physicians (60.0%) tended to draw a pedigree (48.0% in 2007 survey). The rate of genetic test recommendations for patients at risk for HBOC was higher in the 2009 survey (84.0%) than that in the 2007 survey (64.0%). Physicians tended to select a BRCA genetic testing candidate more appropriately than in the previous survey (42.4% answered right in 2007 survey; 74.4% in 2009 survey). Fifteen of 25 participants (60.0%) provided genetic counseling before their patients underwent a genetic test, which was higher than that (40.0%) in the 2007survey. According to the 2009 survey, half of the genetic counseling was being conducted by KOHBRA study research nurses; whereas most of the genetic counseling was conducted by physicians in 2007. Conclusion: The KOHBRA study has played an important role in the appropriate selection of candidates for genetic testing. However, more effort should be placed on improving the pre-test genetic counseling rate.
Purpose: Little is known about long term results of nippleareola preserving skin-sparing mastectomy (NASSM), and there are no such reports on this from South Korea. We studied 5 years follow up results of NASSM and skin sparing mastectomy (SSM) and compared clinical outcomes between NASSM and SSM. Methods: Two hundred two patients who underwent SSM (69 patients) or NASSM (133 patients) from September 1996 to December 2006 were included. Frozen section analysis of retroareolar resection margin was done to make the decision on preserving or not preserving nippleareolar complex (NAC). In the case of positive result on the frozen section, NAC was sacrificed. The local relapse (LR) rate and local relapse free survival (LFS) were analyzed for comparing between NASSM and SSM. Results: The mean age was 40.2 years (range, 24-65), the mean follow-up was 67.6 months. 52 NACs (25.7%) were involved by tumor cells. The invasion to the NAC by tumor cell was more common for invasive carcinoma with extensive intraductal component p<0.001), central located tumor (p=0.025) and invasive carcinoma with multiplicity (p=0.001). There were 12 cases (9.0%) of local relapse in NASSM group and 4 (5.8%) in SSM group, but there was no significant correlation for the LR rate (p>0.05). Regional or distant recurrence after surgical treatment for local relapse occurred in only one SSM case. Five years LFS rate of the NASSM group was 92.1% and that of the SSM group was 95.2%. There was no significant difference for the LFS (p>0.05). Conclusion: Our long term follow up study showed that NASSM and SSM are much alike for their LR rate and LFS. Even if relapse occurs in the NAC, this recurrence cannot affect the progression of relapse after adequate local treatment. Thus, NASSM is alternative method for SSM with oncological safety and better cosmetic outcome.
Purpose: Preoperative tumor size is associated with clinical stage, treatment plan and even survival rate of patient. We investigated the accuracy of tumor size estimation between magnetic resonance imaging (MRI) and ultrasonography (US) findings, comparing these with pathologic tumor size in the diagnosis of early breast carcinoma. Methods: Between 2011 and 2016, 136 patients with early breast cancer were analyzed and their tumor size on US and MRI findings were compared with their pathologic tumor size retrospectively. The background parenchymal enhancement of MRI was categorized as minimal, mild, moderate, and extreme. The patients who underwent neoadjuvant chemotherapy, had positive resection margins, underwent excisional biopsy for cancer diagnosis, and had non-mass lesions on MRI scans, were excluded. Results: In all, 83.1% of the cases showed concordance between MRI findings and pathologic tumor size within 0.5cm. MRI overestimated the findings by 10.3% and underestimated them by 6.6%; 78.7% showed concordance between US findings and pathologic tumor size within 0.5cm. US overestimated the findings by 5.9% and underestimated them by 15.4%. The tumor size on MRI (r=0.87) showed a stronger correlation to the pathologic tumor size than that on US (r=0.64) in early breast cancer patients. US had a tendency to underestimate the tumor size. The degree of breast parenchyma did not affect the accuracy of the measurement of preoperative tumor size. Conclusion: MRI is relatively more accurate than US for assessing preoperative tumor size in breast cancer patients. US tends to underestimate tumor size.
Purpose: This study aimed to evaluate the survival benefit of different adjuvant chemotherapy regimens in patients with T1-2N0 triple-negative breast cancer. Methods: Of 67,321 patients who were registered in the Korean Breast Cancer Society nationwide database between January 1999 and December 2008, 4,033 patients with T1-2N0 triple-negative breast cancer were included. The overall survival of patients who did not receive adjuvant chemotherapy was compared with those treated with adjuvant anthracycline and cyclophosphamide (AC), 5-fluorouracil, anthracycline, and cyclophosphamide (FAC), or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Results: The median follow-up was 52.5 months. Chemotherapy was used in 87.4% of patients; it was used more commonly in patients with T2 tumors, those who were younger, had a higher histologic grade, and who showed lymphovascular invasion. The 5-year cumulative overall survival rate was 95.4%. Younger age, breast-conserving surgery, and adjuvant chemotherapy were significantly associated with improved overall survival. The 5-year cumulative overall survival rate of patients who did not receive adjuvant chemotherapy and those treated with AC, FAC, and CMF were 92.5%, 95.9%, 95.3%, and 95.9%, respectively. On multivariate analysis, the administration of any adjuvant chemotherapy regimen was significantly associated with improved overall survival (p=0.038). No significant difference in survival benefit was observed among the three different treatment groups. Conclusion: A standard adjuvant chemotherapy regimen with the least drug-related toxicity might be a reasonable treatment for patients with T1-2N0 triple-negative breast cancer.
Purpose: Neoadjuvant chemotherapy (NAC) has become the standard treatment for locally advanced breast cancer. The postoperatively adjuvant systemic treatment is based on the status of the histological and biological markers of either the pre-NAC or the post-NAC. There have been several reports that have demonstrated the changes of the histological and biological markers after NAC. The aim of this study is to investigate the effects of NAC on the expression of the histological and biological markers of breast cancer. Methods: We analyzed the paired pre- and post-NAC tumor specimens from 37 patients with stage IIIA, IIIB or IIIC breast cancer. All the patients received 2 to 6 cycles of anthracycline-containing NAC. Over 6 pieces of pre-NAC tumor specimens were taken by 14 G core needle from multiple sites of a tumor, and the post-NAC specimens were taken at the time of the operation. The histologic grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), c-erbB2, p53, Ki67, CD31 and p-glycoprotein were analyzed in the paired pre- and post-NAC tumor specimens from 37 patients. Results: Twenty five patients (67.6%) revealed significant changes of more than one marker. The markers that showed changes of more than two grades were as follows; histologic grade in 1, ER in 4, PR in 9, c-erbB2 in 4, p53 in 1, Ki67 in 4, CD31 in 9 and pglycoprotein in 5 patients. In 12 patients (32.4%), significant changes were found in the markers that can influence the decision-making for adjuvant treatment (i.e. ER, PR and c-erbB2). The ER/PR status changed from positive to negative in 4 patients and c-erbB2 was changed from positive to negative in 3 patients. Among those patients, the strategy of adjuvant treatment was adjusted according to the changes. Conclusion: The specimens for the histologic and biologic markers of a tumor should be taken before NAC because NAC can have an influence on the expression of the prognostic markers of locally advanced breast cancers, and this may subsequently influence predicting the prognosis and making the decision for adjuvant systemic treatment.
Among many adverse effects of docetaxel, fluid retention is a well recognized, cumulative side effect, but severe fluid retention is rare. We report here on a case of docetaxelinduced severe fluid retention with peripheral edema, pleural effusion, severe ascites and pericardial effusion in a 41-yearold woman. She had been treated with 3 cycles of docetaxel 9 days previously and she was admitted to our hospital due to abdominal distention and mild dyspnea. Radiologic studies revealed pleural effusion, severe ascites and a small pericardial effusion. Diuretics were given for 21 days. The pleural effusion was resolved after treatment with diuretics for 2 days, but the ascites wasn’t resolved until 14 days of diuretics. After treatment with diuretics for 21 days, all the symptoms of the patient were completely resolved. Early detection is mandatory and diuretics are very effective for patient suffering with docetaxel-induced severe fluid retention.
Malignant pleural effusion in breast cancer has been associated with poor prognosis. The response rate of local treatment has been very low and in some case, complications have resulted in death. We investigated the efficacy and safety of paclitaxel, as an intrapleural chemotherapeutic agent. From January 2006 to December 2009, ten breast cancer patients who had developed malignant pleural effusion were infused with intrapleural paclitaxel through a chest tube, which was clamped for 48 hours. The chest tube was maintained until drainage was reduced to less than 50-100 mL/day. The average time spent with a chest tube attached following intrapleural chemotherapy was 9.3 days. During the follow-up period, six patients had no recurrent pleural effusion and two received a second round of intrapleural chemotherapy following which no further pleural effusion recurred. There were no severe side effects except for mild toxicity. It is suggested that intrapleural paclitaxel chemotherapy may be superior to conventional local treatment and may represent an effective treatment modality with low toxicity.