Maspin is a unique serine proteinase inhibitor that has tumor suppressor activity. It has been reported that maspin is expressed in normal human mammary epithelial cells and it is down-regulated during the progression of cancer. However, to date, there is very limited data on the clinical significance of maspin expression in human breast cancer. In this study, maspin expression was assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens of the breast. Also, maspin expression was compared with the clinicopathological factors (age, grade, tumor size and lymph node status), the expression of estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the overall survival in an attempt to assess its prognostic value. The maspin expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was significantly correlated with a higher histologic grade, a larger tumor size, a positive p53 status and shorter survival. There was an inverse association with maspin expression and the PR status. These findings suggest that maspin expression is not down-regulated with the progression of cancer and maspin expression may be associated with a poor prognosis. The immunohistochemical detection of maspin in breast cancers may be helpful for predicting an aggressive phenotype.
Tumor Suppressor Protein p53/metabolism ; Survival Rate ; Serpins/*metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Prognosis ; Ploidies ; Middle Aged ; Humans ; Genes, Tumor Suppressor ; Female ; DNA, Neoplasm/analysis/genetics ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/pathology ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Aged ; Adult

BACKGROUND: Breast cancer is the most common type of cancer in females. Aberrant expression of microRNA-21 (miR-21) has previously been reported in breast cancer tissue. The aim of this study was to investigate expression levels of serum miR-21 in breast cancer patients and evaluate its prognostic value in Chinese females. METHODS: Real-time quantitative (RQ)-PCR was used to analyze miR-21 expression in archived serum, tumor tissue, and adjacent normal tissue from 549 participants (326 with breast cancer, 223 without breast cancer). We also analyzed associations between serum miR-21 expression and breast cancer subtypes and patient prognosis. Recurrence and survival were analyzed by using the multivariate Cox proportional hazards model. RESULTS: Expression of miR-21 was significantly higher in breast cancer tissues compared with normal adjacent breast tissues (P<0.001). The 2(-DeltaDeltaCt) values for serum miR-21 in breast cancer patients versus healthy controls were 9.12+/-3.43 and 2.96+/-0.73, respectively. Multivariate Cox proportional hazards model suggested that serum miR-21 expression was an independent poor prognostic factor for both recurrence (hazard ratio [HR]= 2.942; 95% confidence interval [CI]=1.420-8.325; P=0.008) and disease-free survival (HR=2.732; 95% CI=1.038-7.273, P=0.003) in breast cancer. CONCLUSIONS: Increased serum miR-21 expression level was correlated with poor prognosis of breast cancer patients, indicating that serum miR-21 may be a novel prognostic marker for recurrence and survival of breast cancer patients before resection.
Biomarkers, Tumor/genetics ; Breast/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; MicroRNAs/*blood ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Real-Time Polymerase Chain Reaction

Traditional Chinese medicine (TCM) Xiaoaiping shows a pharmacological activity in treatment of breast cancer. Although neoadjuvant chemotherapy has been more and more widely used in treatment of breast cancer in recent years, no report has been made about the clinical efficacy and mechanism of the combined application of neoadjuvant chemotherapy and Xiaoaiping in treatment of breast cancer. In this study, 66 patients with breast cancer were selected and divided into the control group and the treatment group evenly with the random number table method. All patients received TEC neoadjuvant chemotherapy. On that basis, the treatment group also received the adjuvant therapy of Xiaoaiping injection (60 mL, i. v. , qd). The short-term response rate and the follow-up survival rate of the two groups were observed and compared. Surgical specimens of the patient were collected to observe and compare their expressions of estrogen receptor ER-α36 in breast cancer tissues with the immunohistochemical method. According to the findings, the overall response rate of the treatment group was 78.79%, which was significantly higher than that of the control group (57.58% , χ2 = 5.48, P < 0.05). Compared with the control group, the treatment group showed significant increases in the disease-free survival (DFS) rate and the total survival rate at the 3rd year and 5th year (all P < 0.05) , and a notable reduction in ER-α36 expression in breast cancer tissues (P < 0.05). Based on the our results, Xiaoaiping can significantly enhance short-term ad long-term efficacies of neoadjuvant chemotherapy for breast cancer. Its mechanism may be correlated with the inhibition of ER-α 36 expression in breast cancer tissues.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; mortality ; Combined Modality Therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Treatment Outcome

OBJECTIVE: To evaluate the relationship between response categories assessed by magnetic resonance imaging (MRI) or pathology and survival outcomes, and to determine whether there are prognostic differences among molecular subtypes. MATERIALS AND METHODS: We evaluated 174 patients with biopsy-confirmed invasive breast cancer who had undergone MRI before and after neoadjuvant chemotherapy, but before surgery. Pathology findings were classified as a pathologic complete response (pCR) or a non-pCR, and MRI findings were designated as a radiologic CR (rCR) or a non-rCR. We evaluated overall and subtype-specific associations between clinicopathological factors including the assessment categories and recurrence, using the Cox proportional hazards model. RESULTS: There were 41 recurrences (9 locoregional and 32 distant recurrences). There were statistically significant differences in recurrence outcomes between patients who achieved a radiologic or a pCR and patients who did not achieve a radiologic or a pCR (recurrence hazard ratio, 11.02; p = 0.018 and recurrence hazard ratio, 3.93; p = 0.022, respectively). Kaplan-Meier curves for recurrence-free survival showed that triple-negative breast cancer was the only subtype that showed significantly better outcomes in patients who achieved a CR compared to patients who did not achieve a CR by both radiologic and pathologic assessments (p = 0.004 and 0.001, respectively). A multivariate analysis found that patients who achieved a rCR and a pCR did not display significantly different recurrence outcomes (recurrence hazard ratio, 2.02; p = 0.505 and recurrence hazard ratio, 1.12; p = 0.869, respectively). CONCLUSION: Outcomes of patients who achieved a rCR were similar to those of patients who achieved a pCR. To evaluate survival difference according to molecular subtypes, a larger study is needed.
Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Female ; Humans ; Kaplan-Meier Estimate ; *Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Remission Induction

Determining of HER-2/neu oncogene amplification has become clinically important for managing breast cancer. Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) are currently regarded as the standard methods. Chromogenic in situ hybridization (CISH) was investigated as a new modification with an accurate, sensitive technique. From 1998 to 2002, using CISH and IHC, the amplification and protein expression of the HER-2/neu oncogene were examined using paraffin sections in 130 breast carcinomas and to determine the prognostic role of HER-2/neu for outcome after a follow-up of 24- 64 months. Amplifications by CISH and overexpression by IHC were observed in 28 (22%) and 27 cases (20.8%), respectively. Of the 104 patients, 20 patients (19.2%) with amplification had a shorter disease-free interval (34.9 months vs. 38.0 months in controls) (p=0.372). 15 patients (14.4%) had a disease recurrence, but there is no significant difference between 3 patients amplifying the oncogene and 12 patients without oncogene (20.6 months vs. 19.6 months) (p=0.862). 6 patients (5.8%) of these died. CISH is a useful alternative, particularly for confirming the IHC results. There is no relationship between the early recurrence and the HER-2/neu positive group, but lymph node status was statistically significant.
Adult ; Aged ; Breast Neoplasms/*genetics/metabolism/mortality ; Disease-Free Survival ; Female ; Follow-Up Studies ; Genes, erbB-2/*genetics ; Human ; Immunohistochemistry ; In Situ Hybridization ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; *Oligonucleotide Array Sequence Analysis ; Prognosis ; Protein Array Analysis ; Receptor, erbB-2/biosynthesis ; Sensitivity and Specificity ; Support, Non-U.S. Gov't ; Treatment Outcome

We evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab as firs-tline chemotherapy in women with HER2-overexpressing metastatic breast cancer (MBC), and we investigated the prognostic factors including magnitude of HER2/neu amplification in this population. We analyzed 54 patients with HER2-overexpressing MBC that were treated with weekly paclitaxel plus trastuzumab as first-line chemotherapy from February 2004 to December 2006. At a median follow-up of 28 months, median time to progression (TTP) was 16.6 months (95% CI, 9.4 to 23.7 months) and median overall survival was 25.6 months (95% CI, 21.8 to 27.3 months). Therapy was generally well tolerated, although three patients (5.5%) experienced reversible, symptomatic heart failure. Of the 27 patients evaluable for the HER2 FISH, patients with a HER2/CEP17 ratio of < or =4.0 had significantly shorter TTP than those with a HER2/CEP17 ratio of >4.0 (10.8 vs. 23.2 months, P=0.034). A HER2/CEP17 ratio of >4.0 was identified as significant predictive factor of TTP by multivariate analysis (P=0.032). The combination of weekly paclitaxel plus trastuzumab as first-line chemotherapy is an effective regimen in patients with HER2-FISH-positive MBC. Furthermore, the magnitude of HER2 amplification is an independent predictive factor of TTP.
Adult ; Aged ; Antibodies, Monoclonal/*administration & dosage/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/therapeutic use ; Breast Neoplasms/*drug therapy/mortality/pathology ; Disease Progression ; Drug Administration Schedule ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Paclitaxel/*administration & dosage/therapeutic use ; Predictive Value of Tests ; Receptor, erbB-2/*genetics/metabolism ; Survival Analysis