Jing Song Lu

p21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis.

p21/waf1/cip1 and mdm‐2 are downstream effectors of p53. p21 plays a major role in negatively regulating cell‐cycle progression, while mdm‐2 inhibits p53 effects, and its role has been implicated in oncogenesis. In this study, we investigated the expression profiles of p21, mdm‐2 and p53 in human breast‐carcinoma tissues. The aim was to determine whether a correlation exists between the expression profiles of these markers and tumor differentiation, ER status and prognosis. We studied tumor specimens obtained from 106 patients and found a highly significant association among low histology grade, p53 over‐expression, high mdm‐2 expression and lack of p21 expression. Our studies also demonstrate that, in human breast cancer, low levels of p21 and higher mdm‐2 levels directly correlate with the onset of lymph‐node metastases and shortened patient survival. Furthermore, the expression profiles of p21, mdm‐2 and p53 were independently correlated with patient survival. Int. J. Cancer 74:529–534, 1997.

Significance of Apoptosis and Apoptotic-Related Proteins, Bcl-2, and Bax in Primary Breast Cancer

Abstract: Apoptosis and expression of apoptosis‐regulating proteins, Bcl‐2 and Bax, have been observed in human breast carcinomas. The authors investigated whether expression of Bcl‐2 and Bax proteins and apoptotic index (AI) had significance in cases of primary breast cancer. The authors evaluated Bcl‐2 and Bax immunoreactivity and AI in primary breast cancers with the ApopTag method in 91 breast cancer patients retrospectively with long‐term follow‐up (median 60 months). Bcl‐2 expression was seen in 60 (65.9%) cases and Bax expression was observed in 59 (64.8%) cases. Increased Bcl‐2 and absence or low Bax immunoreactivity were significantly associated with low AI, high tumor grade, axillary lymph node involvement, postoperative recurrence, and metastasis. Thirty‐five (38.5%) samples expressed high AI, which correlated with low tumor grade, absent axillary lymph node metastasis, and low levels of Bcl‐2 with Bax overexpression. In univariate analysis, the variables associated with short relapse‐free survival (RFS) and overall survival (OS) were large tumor size, axillary lymph node involvement, high histologic grade, low AI, high Bcl‐2 expression, and absence or low Bax expression. In multivariate analysis, only Bcl‐2 expression, lymph node status, and histologic grade were of independent prognostic value with respect to RFS and OS. Because the vast majority of the patients in this study received chemotherapy, it can be concluded that these apoptotic markers were also predictive of response to chemotherapy. Immunostaining of apoptosis‐related genes, Bcl‐2 and Bax, together with AI, may stratify high‐ versus low‐risk breast cancer patients.

Adjuvant Therapy of Breast Cancer with Pirarubicin Versus Epirubicin in Combination with Cyclophosphamide and 5-fluorouracil

Abstract:  We performed a retrospective study of 856 breast cancer patients in our hospital, to compare the therapeutic effect of pirarubicin with cyclophosphamide and 5‐fluorouracil (CPF) with the standard epirubicin‐based regimen (CEF) in adjuvant treatment of breast cancer. Patients were given cyclophosphamide and 5‐fluorouracil 500 mg/m2 each, and either pirarubicin 40 mg/m2 or epirubicin 75–100 mg/m2, every 3 weeks, six cycles. A total of 233 patients used CPF and 623 patients used CEF regimen. The clinical and pathologic characteristics were well balanced between the two groups. The median follow‐up time was 41 months, relapse‐free survival (RFS) and overall survival (OS) were similar in both groups, p = 0.561 and p = 0.783, respectively. No treatment‐related congestive heart failure or death was observed in either group. Regardless of chemotherapy regimens, only tumor size, lymph node status, and ER status were predictive factors in multivariate survival analysis. In stratified analysis, the total hazard ratio estimate for RFS was 0.876 (95% CI 0.561–1.369; p = 0.562), not in favor of either regimen, and no significant difference was observed in any subgroups between the two treatment arms. Our study verified that 3 weekly CPF gives the same efficacy and safety as the standard CEF; both CPF and CEF are the effective regimens that can be used in adjuvant chemotherapy of breast cancer.

Retrospective analysis of 119 Chinese noninflammatory locally advanced breast cancer cases treated with intravenous combination of vinorelbine and epirubicin as a neoadjuvant chemotherapy: a median follow-up of 63.4 months

BackgroundThis study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC).MethodsOne-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67).ResultsPatients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively).ConclusionThis study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.

Addition of Adjuvant Tamoxifen to Cyclophosphamide, Methotrexate and 5-Fluorouracil for Premenopausal Women with Oestrogen Receptor-Positive Breast Cancer

OBJECTIVE To study the value of adjuvant tamoxifen (TAM) in premenopausal women with oestrogen receptor (ER)-positive breast cancer who received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) polychemotherapy. METHODS Four hundred and two premenopausal ER-positive breast cancer patients who received CMF chemotherapy between January 1990 and December 1999 were retrospectively studied. Disease-free survival (DFS) and overall survival (OS) were used to evaluate the clinical value of TAM therapy. The relationships between nodal status and TAM were also analysed. RESULTS After a mean of 41 months of follow-up, 43 (13.7%) patients died of breast cancer and 68 (19.9%) patients suffered recurrence. There was a significant difference between TAM and non-TAM treatment groups for DFS (p=0.0058), but no significant difference for OS. For node-negative patients, there was no significant difference between the TAM and non-TAM treatment groups for either DFS or OS. For node-positive patients, the difference between TAM and non-TAM treatment groups was significant for both DFS and OS (p=0.0497 and p=0.0285, respectively). CONCLUSION TAM resulted in additional benefit to premenopausal patients with node-positive ER-positive breast cancer who received the CMF polychemotherapy regimen.