p53 Mutation and c-erbB2 Over-expression in Predicting Factor of Responsibility to Neoadjuvant Chemotherapy in Patients with Breast Cancer

PURPOSE: The predictive value of c-erbB2 over-expression, and p53 mutation, to the response rate to neoadjuvant chemotherapy, were assessed in patients with breast cancer. METHODS: Between January 2000 and June 2002, 185 patients, with breast cancer, were put forward for two commonly used chemotherapy regimens prior to surgery. The first 135 received the CMF (cyclophosphamide 600 mg/m2, methotraxate 40 mg/m2, 5-FU 500 mg/m2) regimen, and the remaining 50 the CAF (cyclophosphamide 600 mg/m2, adriamycin 50 mg/m2, 5-FU 500 mg/m2) regimen. The expressions of the estrogen receptor (ER), progesterone receptor (PR), p53 mutation and c-erbB2, were evaluated by immunohistochemistry of needle biopsy samples prior to neoadjuvant chemotherapy. Tumor response was categorized according to the WHO criteria, using the largest diameter in ultrasonography or magnetic resonance imaging. RESULTS: The mean age of the patients in the CMF and CAF groups were 48.8 and 47.4 years. Forty eight (35.6%) and 24 (48.0%) of the patients, in the CMF and CAF groups, respectively, had pathologically partial or complete responses. The tumor size, axillary lymph nodes, lymphatic and vascular invasions, as clinicopathological factors, were significantly correlated with the response to chemotherapy in the CAF group. The absences of ER or PR were also significantly associated with a remission in both the CMF and CAF groups. p53 mutation was not correlated to the response rate of either chemotherapy regimen. There was no significant relationship between the expression of c-erbB2 and the response rate in the CMF group, but a higher percentage of patients with c-erbB2 positive tumors had a response to the CAF regimens. CONCLUSION: p53 mutation is not significantly associated with tumor response, but the over-expression of c-erbB2 can predict the response to the different chemotherapies used in breast cancer.

The Expression of Thymidylate Synthase in Breast Cancer / 한국유방암학회지

Fluorouracil is well known as a standard chemotherapeutic drug in breast cancer and other cancers that is converted to flurodeoxyuridine monophosphate (FdUMP) and leads to the inhibition of thymidylate synthase (TS) in tumor tissue. The role of this enzyme is the catalysis of the methylation from deoxyuridine monophosphate (dUMP) to deozythymidine monophosphate (dUMP), which is a very important process for DNA synthesis in tumor tissues. Increased level of TS protein correlates inversely with sensitivity and response to 5 FU in human cancer cell lines. Authurs evaluated the TS expression level using the immunohistochmical staining and analysed their relationship with other prognostic factors and clinical outcome of breast cancer patients. The results were as follows; 1) TS level was not related histopathologic stage, involvement of axillary lymph nodes, estrogen receptor, progesterone receptor, recurrent type, primary tmor and recurrent tumors, disease free survival rate. 2) TS level was associated with e-erbB2 overexpression. 3) c-erbB2 overexpression was related with recurrence rate. 4) TS level appeared to be related with recurrence rate. So w conclude the TS level can be used as an independant prognostic predictor on breast cancer patients.

Overexpression of c-erbB2 and Its Relationship with Chemotherapy in Breast Cancer / 대한암학회지

PURPOSE: c-erbB2 encodes 185 kDa oncoprotein with tyrosine kinase activity and has homology to the epidermal growth factor receptor. c-erbB2 proto-oncogene is found to be overexpressed in approximately 20 to 30% of primary breast cancer and has been associated with poor prognosis and lower response to conventional chemotherapy. MATERIALS AND METHODS: We perfonned a study on 40 infiltrating ductal breast cancers treated with primary surgery and adjuvant chemotherapy. We investigated c-erbB2 expression by immunohistochemistry in paraffin-embedded tissue using polyclonal antipeptide antibody(DAKO). We evaluated the relationships between its expression and the results after over 6 cycles of adjuvant chemotherapy including cyclophosphamide, methotrexate and 5-FU. RESULTS: The median age at diagnosis was 43 years and the median follow-up time was 47.3 months. Thirteen(32.1%) of 40 patients showed the c-erbB2 overexpression in the external domains of protein. There were no correlations among c-erbB2 amplification and other prognostic factors such as hormonal receptors, histologic grade and tumor size. Estrogen receptor and progesterone receptor showed tendency of inverse correlation with c-erbB2 overexpression but it was not statistically significant(p>0.05). c-erbB2 positive patients showed shorter disease free survival compared to c-erbB2 negative patients in univariate analysis(p0.05). CONCLUSION: These findings suggest that overexpression of c-erbB2 may be a marker of poor response to adjuvant chemotherapy with CMF regimen and may be an indicator of more aggressive therapy.