[show abstract][hide abstract] ABSTRACT: Neo-adjuvant chemotherapy for breast cancer substantially benefits patients who achieve pathological response. However, clinical
or pathological response information can only be obtained a period of time after chemotherapy. The identification of novel
bio-markers or the application of new technique that can be used to predict treatment response before chemotherapy would allow
therapy to be tailored on an individual patient basis. The purpose of this study is to identify the chemo-sensitivity and
chemo-resistance related proteins using antibody microarray profiling, and to develop a multi-protein predictive model for
breast cancer. Total protein was extracted from core needle biopsy samples obtained from 15 patients before treatment with
neo-adjuvant TA (combination of taxanes and anthracycline) chemotherapy. Protein profiling was analyzed by antibody microarray.
10 patients were used as training set to develop the predictive model using the software PAM(prediction analysis of microarray).
Another 5 patients were used as a validation set to test the model. In cross-validation, the molecular predictive model showed
an accuracy of 90%, in independent validation, the model classified the cases with an accuracy of 80%. In conclusion, the
proteomic predictive model has the potential to predict pathological response to neo-adjuvant TA chemotherapy.
KeywordsBreast cancer–Proteomic profiling–Antibody microarray–Neo-adjuvant chemotherapy–Predictive model
[show abstract][hide abstract] ABSTRACT: Nodal staging in breast cancer is a key predictor of prognosis. This paper presents the results of potential clinicopathological predictors of axillary lymph node involvement and develops an efficient prediction model to assist in predicting axillary lymph node metastases. Seventy patients with primary early breast cancer who underwent axillary dissection were evaluated. Univariate and multivariate logistic regression were performed to evaluate the association between clinicopathological factors and lymph node metastatic status. A logistic regression predictive model was built from 50 randomly selected patients; the model was also applied to the remaining 20 patients to assess its validity. Univariate analysis showed a significant relationship between lymph node involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression. Absence of Kiss-1 remained significantly associated with positive axillary node status in the multivariate analysis (p = 0.018). Seven clinicopathological factors were involved in the multivariate logistic regression model: menopausal status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.702 when applied to the validation group. Moreover, there is a need discover more specific candidate proteins and molecular biology tools to select more variables which should improve predictive accuracy.
[show abstract][hide abstract] ABSTRACT: Triple negative breast cancer(TNBC)is characterized by estrogen receptor (ER) negative, progesterone receptor (PgR)negative and human epidermal growth factor receptor 2 (HER-2) negative. It is a high risk breast cancer that lacks the benefit of specific therapy targeting these proteins. In this study, we compared the response to neoadjuvant chemotherapy and disease free survival between patients with TNBC and non-TNBC.
151 patients were included in this study, who received neoadjuvant taxane and anthracycline-based chemotherapy at Peking University People's Hospital from 2002 to 2007. TNBC is defined by the lack of ER, PgR, and HER-2 expression by immunohistochemistry. Clinical and pathologic parameters, pathologic complete response(pCR)rates and survival measurements were compared between patients with TNBC and non-TNBC.
21 of 151 patients (14%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates(38% v 12%; p=0.002), but decreased disease-free survival rates(p=0.004). If pCR was achieved, patients with TNBC and non-TNBC had similar survival (p=0.497).
Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR achieved excellent disease free survival. However, patients who did not get pCR have significantly worse survival if they have TNBC compared with non-TNBC.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2009; 36(2):255-8.
[show abstract][hide abstract] ABSTRACT: Neoadjuvant chemotherapy of epirubicin plus paclitaxel was administered to 75 patients (including a 2-cycle group of 39 patients and a 4-cycle group of 36 patients) with locally advanced breast cancer (35 cases of stage IIb, 28 of stage IIIa, 12 of stage IIIb) to compare efficacy and toxicity of 2 cycle and 4 cycle regimens. All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v., followed by paclitaxel 150 mg/m2, by 3 hour continuous infusion on day 2 repeated every 3 weeks. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteritic and allergic reactions before chemotherapy. Thirty-nine patients were given 2 cycles and thirty-six were given 4 cycles of this regimen. One of 39 patients had complete response, 28 had partial response and 10 had no change in the 2-cycle group. In addition, 21 of 36 patients had complete response (including 9 who had pathologic complete response), 13 had partial response and 2 had no change. The response rates were 74% (29/39) in the 2-cycle group and 94% (34/36) in the 4-cycle group. There were no progressive disease in these 2 groups. However a higher proportion of PR was observed in stage II patients than in stage III patients. Twelve of 36 patients underwent breast conserving surgery, as tumor size had become smaller and down-staging was realized after neoadjuvant chemotherapy. In addition, axillary lymph nodes were palpable in all 75 patients before neoadjuvant chemotherapy with the ET regimen. But 46% (18/39) in the 2-cycle group and 75% (27/36) in the 4-cycle group became impalpable. Conversely, major toxicities (including leukopenia and gastroenteric reactions) were similar in both groups, but myalgia, arthralgia, neurotoxicity and alopecia were more severe in the 4-cycle group than in the 2-cycle group. In the present study, neoadjuvant chemotherapy with a 4-cycle ET regimen was more effective than with a 2-cycle regimen in down staging locally advanced breast cancer. Although major toxicities were more severe in the 4-cycle group than in the 2-cycle group, the regimen was tolerable and safe.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2004; 31(2):205-8.
[show abstract][hide abstract] ABSTRACT: To investigate the effect of mitogen-activated protein kinase (MAPK) signal cascade in the non-estrogen antagonistic mechanism of tamoxifen (TAM).
Human breast cancer cells MCF-7 were cultured. TAM, PD98075, inhibitor of MAPK kinase (MEK), or TAM + PD98075 was added into the culture media, followed by methyl thiazolyl tetrazolium (MTT) and DMSO. Then the 542nm absorption value was measured and the growth curve was drawn. Western blot was used to measure the expression of p-extracellular signal-regulated kinase (ERK) in MCF-7 cells. Flow cytometry was applied to analyze the cell cycle and apoptosis.
The optical density representing the relative expression of p-ERK was lower successively in the control, TAM, PD09875, and TAM + PD09875 groups. The apoptotic rate of MCF-7 cells was 6.44%, 8.3%, 36.5% and 53.5% in the control, PD98075, TAM, and TAM + PG98075 groups respectively The rate of cells in G(0)G(1) phase was 74.25%, 79.76%, 84.02%, and 95.82% in those groups respectively. Ther rate o cells in S phase was 21.03%, 15.22%, 11.43%, and 2.22% respectively in those groups. The rate of cells in G(2)M phase was 4.71%, 5.02%, 4.52%, and 1.96% respectively in those groups.
MAPK signal transduction pathway plays a certain role in the non-estrogen antagonistic mechanism of tamoxifen.
[show abstract][hide abstract] ABSTRACT: Neo-adjuvant chemotherapy of epirubicin plus paclitaxel was administered to 23 patients with locally advanced breast cancer (including 13 cases of stage IIb, 6 of stage IIIa, and 4 of stage IIIb). All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v. followed paclitaxel 150 mg/m2 by 3 hours continuous infusion on day 2 and every 3 weeks repeatedly. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Two to 4 cycles were used. Ten out of 23 patients had a complete response, 10 had partial response, and 3 had no change. The response rate was 87% (20/23). Six out of 23 patients underwent breast conserving surgery as tumor size had become smaller and downstaging was realized after neo-adjuvant chemotherapy. The major toxicities included neutropenia, myalgia, arthralgia, nephrotoxicity, gastroenteric reactions, alopecia and flushing to the face. However, these were well tolerated in these patients.
Gan to kagaku ryoho. Cancer & chemotherapy 08/2002; 29(7):1147-52.
[show abstract][hide abstract] ABSTRACT: To compare the efficacy and toxicity of two different regimens as neoadjuvant chemotherapy for breast cancer.
Forty-eight patients with stage II, III breast cancer as proved by cytology biopsy, were treated with either 5-Fu, epirubicin, cyclophosphamide (FEC) or epirubicin, paclitaxel (ET) regimens for 2 cycles every 3 - 4 weeks. Clinical responses in the breast and lymph nodes were assessed after 2 cycles of neoadjuvant chemotherapy. Patients in FEC arm received combination of 5-fluorouracil (5-Fu) 500 mg/m(2) by 4-hour continuous infusion on D1 and D8, epirubicin (EPI) 50 mg/m(2) by intravenous injection on D1, and cyclophosphamide (CTX) 500 mg/m(2) by intravenous injection on D1 and D8. Patients assigned to the ET arm received EPI 60 mg/m(2) by intravenous injection on D1, paclitaxel (TAX) 150 mg/m(2) by 3-hour continuous infusion on D2. All patients were treated by operation 2 weeks later and radiotherapy was added to some.
For primary tumor in the breast, the overall response rate (RR) was 50.0% (12/24) in FEC arm and 79.2% (19/24) in ET arm. One patient showed clinical complete response (cCR), 11 partial response (PR), 12 no change (NC) after the FEC therapy, while 1 patient showed CR, 18 PR, 5 NC after ET therapy. There was no pathologic complete response or progressive disease, though a higher proportion of RR was observed in stage II than stage III patients in these two groups. Clinically palpable axillary lymph nodes which had been found in all 48 patients before 2 cycles of treatment, 50.0% (12/24) in the FEC patients and 66.7% (16/24) in the ET patients became in-palpable. The major toxicity, including leukopenia, gastroenteric reactions, were similar in both groups, but alopecia was more severe and arthralgia, myalgia, neurotoxicity and flushing of face were the unique features of the ET regimen.
Neoadjuvant chemotherapy with two different regimens were effective to the primary tumor and axillary metastatic lymph nodes of breast cancer, and the side effects were tolerable. Higher efficacy and more side effects are observed in ET than in FEC regimen.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2002; 24(3):303-5.