Research progress on recurrence and metastasis factors for node negative breast cancer and its impact on treatment decisions / 实用肿瘤学杂志

Node negative breast cancer is a prevalent form of breast cancer .With the improvement of breast cancer screening and disease awareness ,the rates of node negative breast cancer are gradually increasing . Although node negative breast cancer patients have much lower recurrence rates as compared with node positive patients,node-negative breast cancer is unequal to a low risk disease .Thus,it is important for oncologist to esti-mate the risk factors of node negative disease ,to carry out risk assessment and to guide the best regimen for these patients.In current review ,we discuss the value of traditional prognostic factors and new prognostic factors ,such as the urokinase -type plasminogen activator/plasminogen activator inhibitor 1,oncotype DX,MammaPrint and tumor associated macrophages ,on the predictive and treatment decisions in node negative breast cancer .

Prognostic Factors Influence on the Systemic Recurrence in Axillary Lymph Node Negative Breast Cancer

PURPOSE: Axillary lymph node metastasis is one of the most important prognostic factors in breast cancer. Previous reports show differences that clinicopathologic factors influence the systemic recurrence and survival in axillary lymph node negative breast cancer. Thus, we have attempted to determine the prognostic factors influence on the systemic recurrence and survival in axillary lymph node negative breast cancer. METHODS: We retrospectively reviewed the data of 1,351 node negative breast cancer patients who underwent curative surgery to determine the prognostic factors such as age, sex, body mass index (BMI), family history, bilateral breast cancer, operation method, tumor size, stage, histologic grade, number of resected lymph nodes, hormone receptor status, overexpression of p53 and c-erbB2, and adjuvant therapy that influence the systemic recurrence and 10-year-distant relapse-free survival. RESULTS: Systemic recurrence occurred in 58 patients (4.3%) during 53.3 months median follow up period. The tumor size (P=0.001), stage (P=0.005), histologic grade (P=0.049). ER (P=0.028), PR (P=0.002), overexpression of p53 (P=0.001) and bilateral breast cancer (P=0.043) were statistically significant factors that influenced the systemic recurrence. In multivariate analysis, only tumor size was associated with the systemic recurrence (P=0.003). Tumor size (P=0.004), histologic grade (P=0.035), ER (P=0.046), PR (P=0.001) and bilateral cancer (P=0.003) were statistically significant factors that influenced 10-year-distant relapse-free survival. CONCLUSION: The larger tumor size was determined to be an independent prognostic value in axillary lymph node negative breast cancer.

Usefulness of Ki-67 as a prognostic factor in lymph node-negative breast cancer / 한국유방암학회지

PURPOSE: To evaluate the independent prognostic value of Ki-67 in lymph node-negative breast cancer and the usefulness of Ki-67 when it combined with St. Gallen classification as a guidance of adjuvant chemotherapy for node-negative cancer. METHODS: We retrospectively reviewed the data of 534 patients with lymph node-negative breast cancer who underwent curative surgery between 1998 and 2001 at our institution. Patients were classified according to the guideline of risk groups of St. Gallen consensus and the level of Ki-67 expression. Distant metastasis-free survival (DFS) rates were compared between groups. RESULTS: With a median follow-up of 55 months, the overall 5-year DFS rate was 91.5%. The 5-year DFS rates for patients with high and low Ki-67 tumors (cut-off value: > or = 10%) were 84.6% and 93.7%, respectively (p < 0.001). In a Cox regression model involving potential prognostic factors, high Ki-67 expression could independently predict the risk of distant recurrence (odds ratio = 2.0 [95% confidence interval, 1.03-3.93]). The 5-year DFS rates for patients with average and minimal risk group of St. Gallen classification were 89.3% and 97.5%, respectively. The average risk group was further divided into two subgroups with significantly different prognosis according to the Ki-67 expression (DFS rate: 84.2% vs. 91.5%; p = 0.007). CONCLUSIONS: Ki-67 was an independent prognostic factor in lymph node-negative breast cancer and the combination of Ki-67 expression and the St. Gallen classification could provide a more useful therapeutic guideline for lymph node-negative breast cancer patients.

Usefulness of Ki-67 as a prognostic factor in lymph node-negative breast cancer / 한국유방암학회지

PURPOSE: To evaluate the independent prognostic value of Ki-67 in lymph node-negative breast cancer and the usefulness of Ki-67 when it combined with St. Gallen classification as a guidance of adjuvant chemotherapy for node-negative cancer. METHODS: We retrospectively reviewed the data of 534 patients with lymph node-negative breast cancer who underwent curative surgery between 1998 and 2001 at our institution. Patients were classified according to the guideline of risk groups of St. Gallen consensus and the level of Ki-67 expression. Distant metastasis-free survival (DFS) rates were compared between groups. RESULTS: With a median follow-up of 55 months, the overall 5-year DFS rate was 91.5%. The 5-year DFS rates for patients with high and low Ki-67 tumors (cut-off value: > or = 10%) were 84.6% and 93.7%, respectively (p < 0.001). In a Cox regression model involving potential prognostic factors, high Ki-67 expression could independently predict the risk of distant recurrence (odds ratio = 2.0 [95% confidence interval, 1.03-3.93]). The 5-year DFS rates for patients with average and minimal risk group of St. Gallen classification were 89.3% and 97.5%, respectively. The average risk group was further divided into two subgroups with significantly different prognosis according to the Ki-67 expression (DFS rate: 84.2% vs. 91.5%; p = 0.007). CONCLUSIONS: Ki-67 was an independent prognostic factor in lymph node-negative breast cancer and the combination of Ki-67 expression and the St. Gallen classification could provide a more useful therapeutic guideline for lymph node-negative breast cancer patients.

Prognostic Factors in Axillary Lymph Node Negative Breast Cancer / 한국유방암학회지

PURPOSE: With the increase of early breast cancer patients, the number of node negative breast cancer patients is also on the rise. However, reports show that there is a 20~30% recurrence in node negative breast cancer. Thus, we have attempted to determine the prognostic factors that may affect recurrence and relapse free survival. METHODS: From January, 1980, to June, 1999, 1110 node negative breast cancer patients who underwent curative surgery at the Severance Hospital, Yonsei University College of Medicine, were selected. A retrospective study was done to determine the effects of factors, such as operation method, age, size, type, histologic grade, intraductal components, ER, PR, c-erbB-2, number of lymph nodes removed, adjuvant chemotherapy, hormonal therapy and radiation therapy. RESULTS: The mean age was 47.2 years. The median follow- up period was 88 months. Recurrence occurred in 161 patients. Locoregional recurrence occurred in 64 patients, and systemic recurrence in 129 patients, while 32 patients had both. The 5 years overall survival rate was 93.3%. The rate of locoregional recurrence for a 10 year-period was significantly lower in the mastectomy group compared with that in the breast conservation therapy group (94.7% vs 79.6%, P=0.000). No other prognostic factors except the age affected in locoregional recurrence. There was less systemic recurrence in patients with the age greater than 35, with the histologic grade I, and with the intraductal components greater than 20%. Thus, 10-years distant relapse free survival rates were 87.4% vs 79.8% (P=0.039), 93.5% vs 85.5% (P=0.024), and 94.4% vs 82.0% (P=0.007), respectively. There was no statistical significance in the other prognostic factors that influence systemic recurrence. CONCLUSION: The patients' age was determined to be an independent prognostic value in the lymph node negative breast cancer. The histologic grade and intraductal components showed to have significance as prognostic factors for systemic recurrence.

Significance of Akt Expression in Node-negative Breast Cancer

BACKGROUND: Patients with lymph node-negative breast cancer show a 10-year recurrence rate of approximately 20%. In node-negative breast cancer, the prognostic factors are age, menopause, tumor size, hormone receptors, p53, DNA ploidy, Ki-67 index (Ki-67) and c-erbB2. Of these, ErbB2 (the protein of the c-erbB2 gene) is a member of the receptor tyrosine kinase family. Overexpression of ErbB2 is known to regulate cell proliferation, differentiation, growth and apoptosis via the ErbB2/Phosphoinositol 3-Kinase (PI 3-K)/Akt signaling pathway. Therefore, it is important to identify high- risk patients that would benefit from adjuvant therapies related with ErB2. For this purpose, the prognostic relevance of the ErbB2/PI 3-K/Akt pathway was examined in node-negative breast cancer. METHODS: A retrospective analysis was performed on the hospital records of all 72 patients diagnosed with breast cancer, and who underwent surgical treatment between January 1996 and December 2003. Clinicopathological data were compared with the results of immunohistochemical staining using the phospho-specific antibody for the expression of Akt. RESULTS: The mean age of the patient's was 48.6 years. Phospho-Akt (pAkt) was expressed in 24 cases (33.3%), but there was no statistical relationship between pAkt expression and the known prognostic factors of breast cancer. There was no statistical significance in the survival rates between the pAkt positive and negative expression groups (P=0.123). In the ErbB2 positive patients, the expression of pAkt was associated with a shorter disease-free survival (P=0.045), and the disease-free survival was shorter in patients whose tumors expressed pAkt and had a high level of Ki-67 (P=0.040). CONCLUSION: The co-expression of ErbB2 and pAkt positivity implied a poor prognosis in node-negative breast cancer patients, and the co-expression of high Ki-67 and pAkt positivity also revealed a poor prognosis in these patients. These results show that the expression of pAkt could be considered a prognostic marker of node-negative breast cancer with ErbB2 positive expression and high levels of Ki-67.

Overexpression of p53 as a Prognostic Marker in Breast Cancer

BACKGROUND: The treatment plan for breast cancer depends on the axillary lymph-node status. Because of improved screening methods, the number and the proportion of node-negative patients are increasing, leading to a need to search for a reliable prognostic marker. Assessment of prognostic markers, is of major concern for the application of adjuvant treatment regimens, independenent of the axillary lymph-node status. METHODS: The study samples consisting of 96 primary breast cancer tissues were analyzed immunohistochemically for the presence of p53 protein in a paraffin-embedded material. The reaction to monoclonal mouse anti-human p53 protein (DAKO-p53, DO-7) (DAKO, Denmark) produced our experimental data. RESULTS: Nuclear accumulation of the p53 protein suspected to be an independent marker of dedifferentiation, regardless of the lymph-node status. In our study the p53 positivity was 56.25% (54/96), and statistically p53 positivity was not affected by menopausal status, lymph-node metastasis, tumor size, age, presence of the estrogen receptor and the progesterone receptor, and pathologic grading. CONCLUSION: We weren't able to prove statistically that overexpression of p53 is an independent prognostic factor in breast cancer. With more cases of breast cancer involving the monoclonal antibody, a study of the correlation of overall survival and disease-free survival with lymph-node metastasis, pathologic grade, and p53 overexpression is necessary to decide on an early breast-cander treatment modality by using a prognostic marker such as p53.

Analysis of indications for adjuvant treatment in node-negative breast cancer / 中国癌症杂志

Purpose:In order to determine the indications for adjuvant treatment in node-negative breast cancer.Methods:We analyzed 233 cases of node-negative breast cancer. Results:The recurrence ratio of node-negative breast cancer was 7.3 percent. The prognosis was connected with age,menstrual history , position, diameter of tumor and pathology. Among invasive lobule cancer, GradeⅢ and lymphocyte-negative cancer, the recurrence ratio was 28 percent in patients with three factors, 16 percent in patient with two factors, 7 percent in patients with one factor.Conclusions:Node-negative breast cancer cases with high recurrence factors need adjuvant treatment.