Prognostic factors for reoperation of recurrent retroperitoneal sarcoma: The role of clinicopathological factors other than histologic grade.

BACKGROUND AND OBJECTIVES: Reoperation is recommended for resectable retroperitoneal sarcoma (RS) recurrence; however, the long-term overall survival (OS) benefit varies. Although histologic grade is an important OS predictor after primary tumor resection, its prognostic value tends to diminish with subsequent reoperations. The objective of this study was to identify prognostic factors of OS after reoperation for recurrent RS. METHODS: The medical records of 95 patients who underwent resection for RS at Seoul National University Hospital between January 1999 and July 2011 were retrospectively reviewed. Of the 95 patients, 50 patients underwent second resection for recurrence, and 26 of these patients underwent third resection. Prognostic factors were analyzed at each reoperation. RESULTS: Higher histologic grade and gross residual disease were poor prognostic factors of OS after first resection. After second resection, higher histologic grade and time since previous operation of within 1 year were poor prognostic factors. After third resection, only contiguous organ resection was a significant independent prognostic factor. CONCLUSIONS: The significance of prognostic factors changes with repetitive reoperations for RS recurrence. The prognostic value of histologic grade diminishes after the third resection, whereas other clinical factors such as time since previous operation and contiguous organ resection achieve significance.

Increasing nodal ratio is a poor prognostic factor for survival in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant chemotherapy: a retrospective study.

OBJECTIVE: The aim of this study is to evaluate the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin in gastric cancer patients and to assess prognostic factors affecting relapse and survival. METHODS: We retrospectively reviewed the data of 153 patients with Stage III-IV (M0) gastric cancer. The patients were given adjuvant 5-fluorouracil/cisplatin chemotherapy after curative gastric resection with D2 dissection from November 1995 to November 2003. Chemotherapy consisted of cisplatin (60 mg/m(2) as 15 min i.v. infusion) and 5-fluorouracil (1200 mg/m(2) as 12 h continuous i.v. infusion for 4 days) in every 21 days up to six cycles. RESULTS: During a median follow-up period of 72.9 months (range: 2.0-135.0 months), a total of 105 patients relapsed (locoregional 19.0% vs. systemic 81.0%). The median disease-free survival and overall survival were 19.8 and 32.2 months, respectively. Univariate analysis revealed T stage, TNM stage and lymph node ratio as prognostic factors for survival (P = 0.002, <0.0001 and <0.0001, respectively). After stepwise selection of the factors, multivariate analysis confirmed the impact of the lymph node ratio and T stage on overall survival and disease-free survival. CONCLUSIONS: In patients with Stage III-IV (M0) gastric cancer, adjuvant 5-fluorouracil/cisplatin chemotherapy was tolerable, but did not seem to confer survival advantage. And the lymph node ratio was found as an independent prognostic factor in this population. This evidence suggests that the clinical trial using more active chemotherapeutic agents is mandatory.

Clinical characteristics of gastric cancer associated with pregnancy.

BACKGROUND/AIMS: This study was conducted to evaluate the clinical features and treatment outcome of gastric cancer associated with pregnancy. METHODS: Clinicopathologic characteristics of 15 patients who were diagnosed as having gastric cancer during pregnancy or within 1 year after delivery (the P-related group) were compared with those of 53 age-matched pregnancy-unrelated gastric cancer patients (the control group). RESULTS: Significant differences were found in tumor stage and surgical curability; the numbers of stage IV disease were 12 (80%) and 21 (40%; p = 0.006), and those of curative resection were 4 (27%) and 20 (62%; p = 0.02) in the P-related and the control group, respectively. Three-year survival rate was significantly lower in the P-related group (23.3%) than in the control group (52.8%; p = 0.007). In the P-related group, only 3 patients, including one patient diagnosed using endoscopy, survived without recurrences. In the multivariate analysis, pregnancy was not identified as an independent risk factor associated with poor outcome. CONCLUSION: Gastric cancer associated with pregnancy is discovered at its advanced stage and consequently shows a dismal prognosis. Considering that the patients who underwent curative resection have a favorable prognosis, primary efforts should be focused on early diagnosis.

Long-term results after excision of breast mass using a vacuum-assisted biopsy device.

BACKGROUND: The excision of breast lesions using an ultrasound-guided vacuum-assisted biopsy device (VABD) is a widely used technique for the diagnosis and treatment of breast disease, but the results of long-term follow-up after VABD excision of benign breast tumours have not been reported. The purpose of this study was to evaluate the results of long-term follow-up after complete excision of benign breast tumours using an ultrasound-guided VABD. METHODS: This is a retrospective clinical study. Between January 2001 and December 2004, patients who had undergone VABD excision of benign breast tumours and been followed up by clinical examination and ultrasonography for 2 years or more were included. RESULTS: One hundred eighty-four cases representing 153 patients were studied. The median follow-up period was 33 months (range, 24-67 months). All lesions were histologically benign. The mean size of the lesions was 1.09 +/- 0.57 cm (range, 0.3-3.03 cm). Within 2 years after VABD excision, residual lesions were detected in 10% of patients sonographically, but after 2 years or more, residual masses were found in 6.5% of patients. Scar changes also decreased from 36.0% to 15.8% during the period of follow-up. Finally, the benign breast tumours were completely excised without residual masses in 93.5% of the participant patients. Residual masses developed in two fibroadenoma cases (1.08%); one was re-excised and the other was followed serially. CONCLUSION: Ultrasound-guided VABD excision is a minimally invasive technique for the complete removal of benign breast tumours. The results of this long-term follow-up of VABD excisions are comparable to conventional methods.

Metastasis-associated protein S100A4 and p53 predict relapse in curatively resected stage III and IV (M0) gastric cancer.

PURPOSE: Pathologic stage is the most important predictive factor of relapse in gastric cancer after curative resection. However, patients with the same stage often have different risks of relapse. Here, we investigated whether the expressions of molecular markers can supplement the current staging system in terms of relapse prediction. PATIENTS AND METHODS: One hundred and nine stage III or IV (M0) patients who had received curative gastrectomy followed by adjuvant 5-fluorouracil and cisplatin chemotherapy were included in this study. The expressions of molecular markers including p53, p27, COX-2, HER-2, EGFR, maspin, S100A4, E-cadherin, Sp1, and p97 were analyzed by immunohistochemistry in cancer and paired normal tissues. RESULTS: The overall relapse rate was 58.7%, and pathologic stage was a significant predictive factor of relapse (42% in stage IIIA, 48% in IIIB, 76% in IV, p = 0.005). Of the 10 markers examined, p53 and S100A4 were expressed only in tumor tissues, and S100A4 expression was significantly associated with a higher relapse rate (85% vs. 53%, p = 0.008). In multivariate analysis including tumor stage, S100A4 and p53 expression were independent predictive factors of relapse (relative risk, 6.98; 95% confidence interval [CI], 1.608-30.342, 3.49; 95% CI, 1.328-9.186, respectively). On comparing patients who expressed S100A4 or p53 with those who expressed neither, relapse rates were 58% vs. 25% in stage III (p = 0.011) and 95% vs. 59% in stage IV (M0) (p = 0.003). CONCLUSION: In addition to staging system, the expressions of S100A4 and p53 were significant predictive factors of relapse in gastric cancer after curative resection and adjuvant chemotherapy.

The use of an in vitro adenosine triphosphate-based chemotherapy response assay to predict chemotherapeutic response in breast cancer.

The adenosine triphosphate-based chemotherapy response assay (ATP-CRA) has the advantages of standardization, evaluability, reproducibility, and accuracy, and can be performed on relatively small numbers of tumor cells. A total of 43 patients were enrolled in the present study, and chemosensitivity tests were successfully performed in 40 (93.0%) of these patients. Twenty of the 40 received neoadjuvant chemotherapy or chemotherapy for metastatic breast cancer. The chemotherapy regimens used were doxorubicin plus docetaxel (n=9, 45.0%) or doxorubicin plus paclitaxel (n=11, 55.0%). Mean cell death rate, as determined by ATP-CRA, was lower in non-responders than in responders to therapy (P=0.012). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for ATP-CRA were 78.6%, 100%, 100%, 66.7%, and 85.0%, respectively. Diagnostic accuracy achieved by immunohistochemistry using estrogen receptor or progesterone receptor was lower than that achieved using ATP-CRA. Expression of p53, erb-B2, Ki67, Bcl-2, Bcl-xL, and annexin I was not significantly associated with response to chemotherapy. Our results show that ATP-CRA has high specificity and positive predictive value for predicting response to chemotherapy.

Expression of Krüppel-like factor 5 in human gastric carcinomas.

PURPOSE: Krüppel-like factor 5 (KLF5) is a zinc finger transcription factor, which has recently attracted attention because of its important regulatory activities linked to diverse functions such as cell growth, proliferation, differentiation, and tumorigenesis in a number of systems. However, its expression in human gastric cancer has not been described previously. In this study, we investigated the expression profile of KLF5 and the relationship between its clinicopathologic features and expression in gastric carcinomas. METHODS: Tissues were obtained from 247 gastric carcinoma patients who underwent curative gastrectomy (R0 resection) at the Department of Surgery, Seoul National University Hospital from January 1995 to June 1995, and these tissues were arranged in tissue array blocks. KLF5 expression was analyzed by immunohistochemical staining using anti-BTEB2 mouse monoclonal antibodies (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). RESULTS: Overall KLF5 was found to be expressed in 45.7% (113/247) of tumor tissues. Moreover, its expression rate was significantly high in early-staged gastric cancer (63.2 vs. 38.0%, p < 0.001), in gastric cancer without lymph node metastasis (54.0 vs. 40.1%, p = 0.04), and in tumors <5 cm in size (53.0 vs. 38.1%, p = 0.02). The 5-year survival rate of patients with KLF5-positive tumors was higher than those of patients with KLF5-negative tumors, although this was not statistically significant (74.7 vs. 62.2%, p = 0.057). CONCLUSION: KLF5 expression rate was high in early-staged gastric cancer, in small gastric cancer tissues and in gastric cancer without lymph node metastasis. By univariate analysis, its expression was found to favor survival after surgery. Our study describes for the first time the expression profile of KLF5 in a large number of human gastric cancer tissues and suggests consistent results shown in many recent studies that reduction of KLF5 expression occurs in many types of human tumor.

Subclassification of pT2 gastric adenocarcinoma according to depth of invasion (pT2a vs pT2b) and lymph node status (pN).

BACKGROUND: We investigated prognostic differences according to nodal status in patients with pT2a and pT2b stage gastric cancers. METHODS: The clinicopathologic outcomes of 1118 patients who underwent curative resection and had 15 or more lymph nodes evaluated for pT2 stage gastric cancers between 1986 and 1996 were reviewed retrospectively. Of the study group, 442 (39.5%) patients had pT2a stage gastric cancers and 676 (60.5%) had pT2b stage gastric cancers. RESULTS: The rates of lymph node metastasis for the pTa and pT2b groups were 53.8% and 71.0%, respectively (P < .001). The disease-specific 5-year survival rate of patients with pT2a cancers was significantly longer than for those with pT2b cancers (85.5% vs 55.7%, P < .001). The prognosis of patients with pT2a gastric cancers was significantly better than that of patients with pT2b cancers on any pN stage (P < .001). Multivariate analysis identified age, pT, and pN stages as independent prognostic factors for patients with pT2 gastric cancers. Patients with pT2aN0 (stage IB) cancers showed the best survival. Patents with pT2aN1 (stage II) and pT2bN0 (stage IB) cancers had similar survival rates, as did patients with pT2aN2 (stage IIIA) and pT2bN1 (stage II) cancers. CONCLUSIONS: The subclassification of pT2 gastric cancers into pT2a or pT2b is necessary to demonstrate their different prognoses. We propose that the current stage grouping should be modified to better represent the prognosis for patients with stage pT2 gastric cancers.

The role of surgery after incomplete endoscopic mucosal resection for early gastric cancer.

PURPOSE: Endoscopic mucosal resection (EMR) is a relatively new treatment option for early gastric cancer (EGC). However, cases of incomplete EMR resulting in a positive lateral margin or submucosal invasion (positive vertical margin) have been reported. We conducted this study to evaluate the role of surgery after incomplete EMR for EGC. METHODS: We analyzed 19 patients who underwent gastrectomy as a result of an incomplete EMR. The patients were divided into three groups according to the type of incomplete EMR: a positive lateral margin (LM) group (n = 9), a positive vertical margin (VM) group (n = 4), and a positive lateral and vertical margin (LM + VM) group (n = 6). RESULTS: The positive residual tumor rate and the positive lymph node rate were 44.4% (4/9) and 0% (0/9) in the LM group, 50.0% (2/4) and 25.0% (1/4) in the VM group, and 83.3% (5/6) and 16.7% (1/6), LM + VM group, respectively. Curative resection was performed in all patients and there was no recurrence in 30.8 months of follow-up. CONCLUSION: Radical surgery is recommended for patients with a positive lateral resection margin or submucosal invasion, or both, after EMR for EGC, because of the possibility of residual tumor or lymph node metastasis.

Negative impact of heat exposure on cosmesis after conservative treatment for breast cancer.

AIM AND BACKGROUND: To identify the factors influencing cosmesis after conservative treatment in breast cancer. METHODS: Retrospective analysis was done on 424 patients who underwent postoperative radiotherapy after conservative surgery for breast cancer from February 1992 to January 2002. Most of the patients underwent quadrantectomy. Whole breast irradiation up to 50.4 Gy was delivered in 28 fractions followed by a 10 Gy boost in 5 fractions to the tumor bed. Regional lymph node irradiation was administered if indicated. Breast cosmesis was scored in 4 tiers. Breast symmetry was analyzed by the relative distance from the sternal notch to the nipple, using photos taken prior to radiotherapy and 2 years after its completion. Median follow-up was 64 months. RESULTS: Breast cosmesis was excellent in 15%, good in 63%, fair in 19%, and poor in 3% of the patients. In multivariate analysis, tumors >2 cm (P = 0.0109), lower quadrant location (P = 0.0026), lymph node irradiation (P = 0.0028), and heat exposure (P = 0.0152) were related to poor cosmesis. The cosmesis score after radiotherapy compared to the pre-radiotherapy score was deteriorated in patients who had undergone lymph node irradiation (P < 0.0001) and heat exposure (P = 0.0027). Breast symmetry was worse for patients who had tumors >2 cm (P < 0.0001), upper quadrant tumor location (P < 0.0001), chemotherapy in combination with radiotherapy (P = 0.0136), lymph node irradiation (P = 0.0006) and heat exposure (P = 0.0355). Changes in symmetry by radiotherapy were greater for lymph node-irradiated patients (P < 0.0001). CONCLUSIONS: With larger tumor size, lymph node irradiation, and chemotherapy in combination with radiotherapy, heat exposure was found to have a negative impact on cosmesis in patients undergoing conservative treatment for breast cancer. Patients should therefore be advised to avoid heat exposure after breast irradiation.

Outcome after emergency surgery in gastric cancer patients with free perforation or severe bleeding.

BACKGROUND/AIMS: This study was conducted to evaluate the clinicopathologic characteristics and surgical outcome of perforated or bleeding gastric cancer patients. METHODS: Twenty-six gastric cancer patients undergoing emergency surgery for free perforation (n = 13) or severe bleeding (n = 13) were reviewed. RESULTS: In the perforation group, tumors were mainly located in the greater curvature and anterior wall, but in the bleeding group, they were mainly in the lesser curvature. Three (23%) patients in the perforation group and 7 (54%) in the bleeding group received potentially curative resections (p = 0.11). The postoperative morbidity rate and mortality rate were 31 (8/26) and 8% (2/26), respectively. Median survival time after operation was 5.5 months. One patient in the perforation group and 3 patients in the bleeding group who underwent curative resection survived more than 30 months without recurrence. Three factors were found to be associated with improved survival after emergency surgery: potentially curative resection; TNM stage, and the absence of postoperative complications. CONCLUSION: Emergency surgery for gastric cancer patients with perforation or severe bleeding is associated with a low curative resection rate and a high postoperative complication rate. However, long-term survival can be expected in those patients who underwent curative resection with earlier stage gastric cancer.

Outcome of hepatic resection for metastatic gastric cancer.

The role of hepatic resection for metastatic gastric cancer is less well defined due to the tendency of gastric cancer to widely metastasize. The purpose of this study is to examine the beneficial effect of hepatic resection in patients with metastatic gastric cancer. The clinicopathologic features and long-term results of 11 patients who underwent hepatic resection for metastatic gastric cancer from January 1988 to December 1996 at Seoul National University Hospital were analyzed retrospectively. All resected hepatic metastases were solitary lesions. Among eight patients with synchronous hepatic metastases, one patient with early gastric cancer and lymph node metastases (T1N2M1) remained alive for 8 years 6 months after hepatic resection without recurrence. Among three patients with metachronous hepatic metastases, two patients with advanced gastric cancer and lymph node metastases (T3N2MO, T2N1MO at the initial operation, respectively) survived 8 years 6 months and 3 years after hepatic resection, respectively. Median survival times of synchronous and metachronous hepatic metastases were 13.0 and 74.3 months, respectively. In solitary hepatic metastatic lesions from gastric cancer, surgical resection should be considered as one of the treatment options.

Growth effect of gastrin on gastric cancer and its clinical implications for gastric cancer surgery.

This study was aimed at investigating the effect of gastrin on the growth of gastric cancer and evaluating postoperative hypergastrinemia in patients that had received various types of gastrectomy for gastric cancer. RT-PCR for gastrin/CCKB receptor mRNA was performed in human gastric cancer cell lines and tissue. The effect of gastrin or glycine-extended gastrin on the growth of gastric cancer cell lines was determined by MTT assay. Serum gastrin levels were compared with respect to the resection type of gastric cancer surgery. Gastrin/CCKB receptor mRNA expression was detected in all 9 gastric cancer cell lines, and in 19 of 29 (62%) gastric cancer tissue samples. Growth of gastric cancer cell lines containing the gastrin/CCKB receptor was significantly enhanced by gastrin and glycine-extended gastrin. The proximal gastrectomy group had a significantly higher mean serum gastrin level than the distal subtotal gastrectomy, total gastrectomy, or preoperative groups (p<0.05). Our study confirms that a high proportion of gastric cancer tissue samples express the gastrin/CCKB receptor, which can stimulate the growth of gastrin/CCKB receptor-positive gastric cancer cells. In addition, we confirm that hypergastrinemia can be induced in about half of patients after proximal gastrectomy. More studies are needed to clarify the relationship between hypergastrinemia and tumor recurrence after proximal gastrectomy.

The clinical use of staging bone scan in patients with breast carcinoma: reevaluation by the 2003 American Joint Committee on Cancer staging system.

BACKGROUND: Using the new 2003 American Joint Committee on Cancer (AJCC) staging system, the authors evaluated the usefulness of the staging bone scan in patients with primary breast carcinoma. METHODS: The authors examined 1939 patients with primary breast carcinoma for staging bone scan who were treated at a single institution. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging systems. RESULTS: Bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.7% (5 of 699) for patients with Stage IIA disease, 2.1% (10 of 479) for patients with Stage IIB disease, 4.5% (7 of 154) for patients with Stage IIIA disease, and 10.5% (2 of 19) for patients with Stage IIIB disease according to the 1988 AJCC staging system. The authors found a significant difference in the bone metastasis rate between patients with Stages IIA and IIB disease in the 1988 staging system (P = 0.039). Reevaluating the patients by the 2003 system resulted in significant upstaging, especially for patients with Stage II/III disease. According to the 2003 staging system, bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.6% (4 of 648) for patients with Stage IIA disease, 0.6% (2 of 310) for patients with Stage IIB disease, 4.0% (9 of 225) for patients with Stage IIIA disease, 16.7% (2 of 12) for patients with Stage IIIB disease, and 4.4% (7 of 158) for patients with Stage IIIC disease. It was noteworthy that there was a significant difference between Stages IIB and IIIA in the 2003 staging system (P = 0.010). CONCLUSIONS: Stage reclassification using the new AJCC staging system resulted in upstaging of high-risk patients, as well as a significant decrease in the bone metastasis rate in patients with Stage IIB breast carcinoma. Considering the cost-effectiveness of staging bone scan, the data suggested that it was of little value for patients with Stage I and II breast carcinoma, but was highly recommended for patients with worse than Stage III disease by the new 2003 staging system.

Expression of chemokine receptors in human gastric cancer.

The roles of chemokine receptors in cancer metastatic processes continue to draw research attention. Here we evaluated the expression profiles of the chemokine receptors CCR7 and CXCR4 in gastric cancer, and their potential use as prognostic markers. The expressions of CCR7 and CXCR4 mRNA were analyzed by RT-PCR in 10 human gastric cancer cell lines and in 43 gastric cancer tissues, and in an additional 307 gastric cancer tissues by immunohistochemistry. Clinicopathological features and the prognoses of patients were also evaluated versus the expression of these two cytokine receptors. CCR7 and CXCR4 mRNA were found to be expressed in all gastric cancer cell lines, whereas their mRNA expression rates in gastric cancer tissues were 83.7% (36/43) and 100% (43/43), respectively. Immunohistochemical staining of the 307 gastric cancer tissues showed that the expression rates of CCR7 and CXCR4 were 22.5% (69/307) and 36.5% (112/307), respectively. Multivariate analysis of the immunohistochemistry results showed that the expression rate of CCR7 was significantly higher in differentiated than in undifferentiated gastric cancertypes (35.1 vs. 15.3%, p<0.001), and that CXCR4 was expressed at a higher rate in intestinal cancer than in diffuse-type cancer (58.8 vs. 22.3%, p<0.001). However, in contrast to previous studies, the expressions of CCR7 or CXCR4 were not associated with lymph node metastasis. Moreover, the prognosis of patients with CCR7-positive tumors was better than that of patients with CCR7-negative tumors, but no such correlation was observed for CXCR4 expression. In conclusion, the expressions of the chemokine receptors CCR7 and CXCR4 were found to be high in differentiated and intestinal-type gastric cancers, respectively.

Lymph node metastasis in early gastric cancer with submucosal invasion: feasibility of minimally invasive surgery.

AIM: To explore the feasibility of performing minimally invasive surgery (MIS) on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS: A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995. Besides investigating many clinicopathological features such as tumor size, gross appearance, and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS: The rate of lymph node metastasis in cases where the depth of invasion was <500 microm, 500-2000 microm, or >2000 microm was 9% (2/23), 19% (7/36), and 33% (15/46), respectively (P<0.05). In univariate analysis, no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age, sex, tumor location, gross appearance, tumor differentiation, Lauren's classification, and lymphatic invasion. In multivariate analysis, tumor size (>4 cm vs <=2 cm, odds ratio = 4.80, P = 0.04) and depth of invasion (>2000 microm vs <=500 microm, odds ratio = 6.81, P = 0.02) were significantly correlated with lymph node metastasis. Combining the depth and size in cases where the depth of invasion was less than 500 microm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm. In cases where the tumor size was less than 2 cm, lymph node metastasis was found only where the depth of tumor invasion was more than 2000 microm. CONCLUSION: MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 microm in depth.

Determining the main risk factors and high-risk groups of breast cancer using a predictive model for breast cancer risk assessment in South Korea.

This study was aimed at developing a predictive model for assessing the breast cancer risk of Korean women under the assumption of differences in the risk factors between Westerners and Koreans. The cohort comprised 384 breast cancer patients and 2 control groups: one comprising 166 hospitalized patients and the other comprising 104 nurses and teachers. Two initial models were produced by comparing cases and the 2 control groups, and the final equations were established by selecting highly significant variables of the initial models to test the accuracy of the models in terms of disease probability and predictability. Both the initial models and the final disease-probability models were confirmed to exhibit high degrees of accuracy and predictability. Major risk factors determined by comparing the patients with hospitalized controls were a family history, menstrual regularity, total menstrual duration, age at first full-term pregnancy, and duration of breastfeeding. Major risk factors determined by comparing patients with nurse/teacher controls were age, education level, menstrual regularity, drinking status, and smoking status. The predictive model developed here shows that risk factors for breast cancer differ between Korean and Western subjects in the aspect of breastfeeding behavior. However, identifying the relationship between genetic susceptibility and breast cancer will require further studies with larger samples. In a model with nurse/teacher controls, drinking and higher education were found to be protective variables, whereas smoking was a risk factor. Hence the predictive model in this group could not be generalized to the Korean population; instead, breast cancer incidence needs to be compared among nurses and teachers in a nurse-and-teacher cohort.

Combined effect of GSTM1, GSTT1, and COMT genotypes in individual breast cancer risk.

Our previous studies suggested that both catechol O-methyl transferase (COMT) and glutathione S-transferase (GST) M1 and T1 genotypes are associated with breast cancer risk. Here we extended the studies to evaluate the potential combined effect of these genotypes in individual breast cancer risk. Incident breast cancer cases (n = 202) and controls (n = 299) with no previous cancer were recruited from three teaching hospitals in Seoul in 1996-1999. Information on putative risk factors was collected by interviewed questionnaire. PCR-based methods were used for the genotyping analyses. Odds ratios (ORs) and 95% confidence (CIs) intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Among pre-menopausal women the low activity associated (COMT *L) allele containing genotypes and the GSTM1 null genotype posed increased risks of breast cancer with ORs of 1.7 (95% CI = 1.0 - 2.8) and 1.7 (95% CI = 1.0-2.8), respectively. A marginally significant effect of GSTT1 null genotype was also observed when the total study population was considered (OR = 1.3, 95% CI = 1.0-2.1). When the combined genotype effects were examined, the concurrent lack of GSTM1 and GSTT1 genes posed a more than 2-fold risk of breast cancer (OR = 2.2, 95% CI = 1.2-3.9); this effect was mainly attributable in pre-menopausal women (OR = 3.2, 95% CI = 1.5-7.2). Moreover, the breast cancer risk increased in parallel with the number of COMT , GSTM1 , and GSTT1 at-risk genotypes (p for trend = 0.003). This association was particularly clear in pre-menopausal women among whom combination of all three high-risk genotypes posed a 4.1-fold breast cancer risk (95% CI = 1.4-12.7) compared with pre-menopausal women without at-risk genotypes (p for trend = 0.001). The trend was more pronounced in women with BMI greater than 22 kg/m2 (p for trend < 0.001) and high-risk status of parity factor (nulliparous or women with the first full term pregnancy at age of over 25-year-old) (p for trend = 0.013). These results suggest the combined effect between reproductive factors and GSTM1, GSTT1 and COMT genotypes in human breast carcinogenesis.

Young age: an independent risk factor for disease-free survival in women with operable breast cancer.

BACKGROUND: The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients. METHODS: We retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups. RESULTS: A total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010). CONCLUSION: Young age (<35) is an independent risk factor for relapse in operable breast cancer patients.

A combination of HER-2 status and the St. Gallen classification provides useful information on prognosis in lymph node-negative breast carcinoma.

BACKGROUND: Adjuvant chemotherapy for patients with lymph node-negative breast carcinoma is being recommended currently based on the St. Gallen classification. The prognostic importance of HER-2 status in patients with lymph node-negative breast carcinoma has been investigated extensively, with contradictory results. The authors investigated the clinical relevance of HER-2 overexpression when combined with the St. Gallen classification in lymph node-negative breast carcinoma. METHODS: The medical records of patients with breast carcinoma negative for lymph node involvement who underwent surgery between January 1995 and December 2000 at the Seoul National University College of Medicine (Seoul, Korea) were reviewed retrospectively. Risk groups based on the St. Gallen classification were categorized as average or minimal risk. The prognostic values of HER-2 in combination with the St. Gallen classification were analyzed with respect to disease-free survival (DFS) rates. RESULTS: A total of 906 patients were eligible for analysis. The overall 7-year DFS rate was 87.5%. The 7-year DFS rates for patients with HER-2-positive and HER-2-negative tumors were, respectively, 77.9% and 91.2% (P = 0.002). The 7-year DFS rates for patients with average and minimal risk group were 85.0% and 97.9%, respectively. The authors found that HER-2 overexpression significantly predicted the risk of disease recurrence (odds ratio = 3.03 [95% confidence interval, 1.63-5.63]). Furthermore, when HER-2 status was combined with the St. Gallen classification, the DFS rate of the HER-2-positive average risk group was 73.3% compared with 88.4% for the HER-2-negative average risk group (P = 0.007). CONCLUSIONS: The combination of HER-2 overexpression and the St. Gallen classification was more useful than either alone to predict the risk of disease recurrence in patients with lymph node-negative breast carcinoma.