Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer.

PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes. METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase. RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%. CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

Human papilloma viruses (HPVs) no co-existence in breast cancer and cervical cells in the same patient.

High-risk HPVs were detected in both breast cancer tissues and cervical cells from 56 breast cancer patients. The results suggested that HPV infection did not coexist in breast and cervical tissues. HPV infection of the breast cancer tissue is more likely to happen in patients without cervical infection.

Clinicopathological significance of CEACAM1 gene expression in breast cancer.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell adhesion molecule expressed in a variety of cell types. The role of CEACAM1 in breast cancer development and progression is largely unknown. Immunohistochemical analysis was used to examine CEACAM1 expression in breast cancer with long-term follow-up. CEACAM1 expression level in primary breast cancer was low or undetectable. In 65% of the cases, CEACAM1 expression within tumor tissue was lower than that in adjacent tissues. In 20% of the cases, CEACAM1 was negative. In 28.3% of cases, equivalent CEACAM1 expression level was detected in tumor and adjacent tissues. The expression level of CEACAM1 in tumor tissue was negatively correlated with patient mortality, while positively correlated with the expression level of ER+/PR+. CEACAM1 expression was not related with patients' age, pathological classification, lymphatic involvement and the size of tumor. The down-regulation of CEACAM1 was correlated with negative ER-/PR- and might be attributed to the malignant process of breast cancer. The prognosis of the patients with low CEACAM1 expression and high tumor pathological grade were poorer than those patients with high expression and low pathological grade, P < 0.05. Clinically, it is possible to predict the prognosis among the patients of breast cancer by measuring CEACAM1 gene expression in the tumor tissues.

Paclitaxel-doxorubicin sequence is more effective in breast cancer cells with heat shock protein 27 overexpression.

BACKGROUND: Cancer cells with overexpression of heat shock protein 27 (HSP27) are resistant to chemotherapeutic drug doxorubicin (Dox). Paclitaxel (Pacl) was reported to suppress HSP27 expression in ovarian and uterine cancer cells. The purposes of this study were to investigate whether Pacl inhibits the expression of HSP27 in breast cancer cells, whether Pacl can sensitize breast cancer cells with HSP27 overexpression to Dox, and to define a more effective schedule for the combination of Dox with Pacl. METHODS: The HSP27 high-expressing human breast cancer cell lines, MCF-7 and MDA-MB-435, and the HSP27 low-expressing cell line, MDA-MB-231, were used in this study. The level of HSP27, topoisomerase (Topo) IIalpha and beta expression were assessed by Western blotting. The cytotoxic activities of Dox, Pacl and combination of these two drugs were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometric assays. RESULTS: Pacl (0.1 micromol/L) inhibited HSP27 expression by approximately 2-fold in MCF-7 and MDA-MB-435 cells, while up-regulating the level of topo IIalpha and beta. In contrast, expression of HSP27 in MDA-MB-231 did not change significantly following Pacl treatment. There were synergistic effects in both treatment sequences (Pacl-Dox and Dox-Pacl) when Pacl was combined with Dox. Compared with those treated with the Dox-Pacl sequence, the Pacl-Dox sequence had a stronger effect in cancer cells with HSP27 overexpression, as MCF-7 and MDA-MB-435 treated with the Pacl-Dox sequence had lower viabilities and a higher apoptotic rate. CONCLUSIONS: Paclitaxel significantly decreases the level of HSP27 in breast cancer cells overexpressing HSP27. In combination therapies, the Pacl-Dox sequence is more effective in clearing breast cancer cells with high HSP27 expression compared with the Dox-Pacl sequence.

Preservation of the continence function after intersphincteric resection using a prolapsing technique in the patients with low rectal cancer and its clinical prognosis.

BACKGROUND: The technique of intersphincteric resection of tumors combined with coloanal anastomosis has been used to avoid permanent colostomy for patients with a rectal cancer located < 5 cm from the anal verge. This study aimed at assessing the preservation of continence function of the residual rectum and the clinical prognosis of patients with lower rectal cancer after intersphincteric resection using a prolapsing technique. METHODS: This study included patients with the following inclusion criteria: (1) pathological evidence of rectal cancer and the tumors within distal margins located 5 cm or less from the anus by preoperative endoscopic examination; (2) no evidence by MRI of infiltration of either the external sphincter, puborectalis or the levator muscle; (3) the patients are eligible for intersphincteric resection and lower coloanal anastomosis with a preoperative biopsy showing the tumors with well-to-moderate differentiation. From January 2000 to June 2004, 23 patients with low rectal cancer were included in this study. We used the standard abdominoperineal approach to perform radical resection of tumors with excision of the mesorectum and total or part of the internal sphincters. The patients were followed for assessment of the function of the residual rectum and of cancer recurrence after the operations. RESULTS: The median tumor distance from the anal margin was 4.5 (range 3.5 - 5.0) cm and the mean distal surgical margin 1.6 (range 1.0 - 2.0) cm. Cancer was classified into Stage I (30.4%), Stage II (47.8%), and Stage III (21.7%) according to the TNM classification. Two patients developed anastomotic fistula after the surgical resection and 2 patients (8.7%) developed later stages of anastomotic stricture at the site of coloanal anastomosis. The median follow-up period was 31.5 months (range 12 - 54) and 2 patients (8.7%) developed local recurrence. Three deaths were associated with distal organ metastasis. Twenty patients (87.0%) have maintained competence to control solid or liquid stool and the capacity of flatus continence after the surgery. Among these patients, 2 patients were able to control solid stool and occasionally lose continence of liquid stool. And only 1 patient (4.4%) has retained partial rectum function with good continence of solid stool but not liquid after the operations. Average times of defecation per day of 3, 6, 12, 24 and 36 months after the surgery were 13.1, 4.7, 3.1, 2.9, and 3.2 times/day. Anal manometer measurements showed a decrease of pressure during the resting time after intersphincteric resection and this change remained during the period of follow-up. The maximum squeeze pressure was improved after an initial decrease after the surgery. CONCLUSIONS: More residual rectum function after the surgery may be preserved by intersphincteric resection of low rectum cancer. At the same time this technique is safe with few postoperative complication and low tumor recurrence after the surgery.

[Inhibitive effects of mifepristone on growth of breast cancer: experiment with animal model].

OBJECTIVE: To investigate the effects of mifepristone (MIF) on the growth of breast cancer. METHODS: Forty female athymic BALB/c-nude mice underwent subcutaneous injection of breast cancer cells of the line MCF-7, ER +/PR +. Ten days later when tumor nodules were formed, the mice were randomly divided into 4 equal groups to be administered with MIF of the concentrations of 25 mg, 50 mg, 100 mg, and 200 mg/kg x d respectively by gastric perfusion. The tumor size was observed every 3 day till 3 weeks later. Ten mice were used as normal control group, undergoing gastric perfusion of vegetable oil. Parts of the animals were killed 2 weeks later, and the remaining mice were all killed 3 weeks later. The tumors were taken out and underwent immunochemistry to measure the protein expression of CD34, estrogen receptor (ER), progesterone receptor (PR), vascular endothelial growth factor (VEGF), bcl-2, Ki67, p53, and CerbB-2. Microscopy was used to measure the microvessel density (MVD). RESULTS: The growth velocity of tumor of the mice of MIF groups were all slower than that of the control group (all P <0.01). The MVD levels of the MIF groups all decreased time- and dose-dependently. Microscopy showed that in the tumor tissues heteromorphism was significant, pathological caryomitosis was more remarkable, karyoplasmic ratio was greater, endochylema was deep blue, mesenchyma was sparse, and zone of neoplasm necrosis became lager in comparison with the control group. The expression levels of VEGF, bcl-2, Ki67, p53, and CerbB-2 of the MIF groups were all significantly lower, time and dose-dependently, than those of the control group (all P <0.05). CONCLUSION: MIF inhibits the growth of breast cancer by the mechanisms related to apoptosis promotion and inhibition of angiogenesis, so it can be used in breast cancer endocrine therapy.

[Relationships among the expression of thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase and the prognosis of breast cancer].

OBJECTIVE: To investigate the relationships among the expression of thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) and the prognosis of breast cancer. METHODS: Immunochemistry (ABC method) was used to detect the expression of TS, TP, and DPD in the samples of breast cancer resected during operation from 28 female patients. The microvessel density (MVD) in the cancer tissue was measured by immunochemistry (LSAB method). RESULTS: The TS positive rate was 30.26% and the TP positive rate was 21%, and the DPD positive rate was 30.03%. The expression levels of TS and TP were both correlated with the tumor size, lymph node status, histological grading of tumor, and microvessel count (MVC) (all P < 0.01), and was not correlated with age, status of estrogen receptors, status of prasterone receptors (all P > 0.05). The DPD expression was not correlated with the age, tumor size, lymph node status, histological grading of tumor, status of estrogen receptors, status of prasterone receptors, and MVC. The ten-year disease-free survival rate of the TS-positive patients was 0, significantly lower than that of the TS-negative patients (25%, P < 0.01). The ten-year overall survival rate of the TS-positive patients was 3.9%, significantly lower than that of the TS-negative patients (58.8%, P < 0.01). The ten-year disease-free survival rate of the TP-positive patients was 0, significantly lower than the TP-negative patients (25.4%, P < 0.01). The ten-year overall survival rate of the TP-positive patients was 0.9%, significantly lower than that of the TP-negative patients (61.8%, P < 0.01). The ten-year disease-free survival rate and ten-year overall survival rate of the DPD positive patients were not significantly different from those of the DPD negative patients (both P > 0.05). MCV and TS expression were strong protective factors of disease-free survival rate and overall survival rate. CONCLUSION: The levels of TS and TP are both prognostic indicis of breast cancer.

[Accuracy of preoperative magnetic resonance imaging in prediction of pathological stage and circumferential resection margin in rectal cancer].

OBJECTIVE: To evaluate the accuracy of preoperative magnetic resonance imaging (MRI) in prediction of pathological staging and involvement of circumferential resection margin (CRM) in rectal cancer. METHODS: Fifty-three patients undergoing total mesorectal excision for biopsy-proven rectal cancer were assessed prospectively using high-resolution MRI for tumour (T) and mesorectal nodal (N) staging as well as CRM status using the depth of tumour spread, tumour node metastasis and CRM involvement. Preoperative MRI assessment of these prognostic factors was compared with the histopathological findings in carefully matched whole-mount sections of the specimen. RESULTS: MRI correctly staged the tumor in 41 patients, understaged in 8, and overstaged in 4. The accuracy of T stage was 77.4% (41/53). There was ageneric correlation between pathologic and MRI tumor staging (Kappa = 0.602, P < 0.001). Node status was correctly staged in 37 patients, overstaged in 10, and understaged in 6. The accuracy of node staging was 69.8% (37/53), sensitivity was 75% (18/24), and specificity was 65.5% (19/29). The correlation between pathologic and MRI node staging was poor (Kappa = 0.399, P = 0.003). The CRM status was correctly reported in 51 patients, overstaged in 1, and understaged in 1. The accuracy of CRM status was 96.2% (51/53), sensitivity was 80% (1/5), and specificity was 97.9% (47/48). There was a good correlation between pathologic and MRI CRM involvement (Kappa = 0.779, P < 0.001). CONCLUSION: Preoperative MRI provides poor predictive data as to subsequent pathologic tumor and mesorectal node stage, but does produce reliable prediction of clear CRM.

[Relationship between expression of thymidylate synthase and colorectal carcinoma].

OBJECTIVE: To study the relationship between the expression of thymidylate synthase (TS) gene and the prognosis of colorectal carcinoma and between the TS expression and the effect of 5-fluorouracil (5-Fu) on advanced colorectal carcinoma. METHODS: 134 formalin-fixed and paraffin-embedded specimens of colorectal carcinoma obtained during operation from 134 patients, 65 males and 69 females, aged 34 approximately 76 with an average age of 51 +/- 11, 16 with differentiated carcinoma and 118 with undifferentiated carcinoma, 4 with infiltration into mucous layer, 21 into submucous layer, 100 into muscular layer, and 5 into serous layer, 25 without lymphatic metastasis and 109 with lymphatic metastasis, 4 in stage IB, 15 in stage II, 90 in stage IIIA, and 27 in stage IIIB by Dukes staging, underwent immunohistochemistry (ABC methods) to determine the expression of TS. After operation all patients received chemotherapy with leucovorin and 5-Fu for 4 approximately 6 periods and were followed up for 9 approximately 72 months. RESULTS: Eighty-two specimens showed high TS expression and 52 showed low TS expression. The grade of TS expression was significantly correlated with four clinicopathologic variables: histological type, depth of invasion, lymphatic metastasis, and Dukes' stage (all P < 0.001). The 5-year survival rate for the low TS group was 57.69%, significantly lower than that of the high TS group (21.95%, P < 0.001). Multivariate analysis revealed that three variables (histological type, depth of infiltration, and TS grade) independently contributed to the survival rate (all P < 0.05), especially the TS grade (all P < 0.0001). The relative hazard ratio of TS grade was 1.241. CONCLUSION: The expression of TS is one of the important prognosis indicators of colorectal carcinoma. It is also a relatively reliable indicator of whether 5-Fu should be used in the treatment of patients with colorectal carcinoma.

[Status of estrogen receptor affects the drug sensitivity of drug-resistant MCF-7/Adr human breast cancer cells to droloxifene and Adriamycin].

BACKGROUND & OBJECTIVE: Loss or decreased expression of estrogen receptor (ER) and decreased growth rate regularly occur in drug-resistant breast cancer cells. This study was designed to investigate the effect of estrogen receptor status on the drug resistance to droloxifene (Dro) and Adriamycin (Adr) of drug-resistant MCF-7/Adr human breast cancer cells. METHODS: The expression of ER in MCF-7 and MCF-7/Adr cells was determined using Western blot analysis. ER expression plasmid was constructed and introduced into MCF-7/Adr cells using LipofectAMINE. After G418 screening, the positive clone (MTER/Adr) was obtained. The integration and expression of ER gene were analyzed by polymerase chain reaction (PCR) and Western blot. The cell cycle distribution was investigated by flow cytometry. The effects of droloxifene and Adriamycin on the growth of cells were investigated by MTT assay. RESULTS: Western blot analysis showed that ER was positive in MCF-7 cells, but was negative in MCF-7/Adr cells. The ER expression plasmid was constructed and introduced into MCF-7/Adr cells. The integration and expression of ER gene were successful in positive clone -MTER/Adr cells. Droloxifene inhibited the growth of MCF-7 at the concentration of 10-20 micromol/L and the MCF-7/Adr only at concentration of 20 micromol/L. Droloxifene inhibited the growth of MTER/Adr at the concentration of 15 micromol/L, and the percentage of MTER/Adr cells increased in G0/G1 phase. The sensitivity of MTER/Adr cells to Adriamycin increased. CONCLUSION: The insensitivity of MCF-7/Adr human breast cancer cells to droloxifene was associated with the loss of ER. MTER/Adr cells partially restore the sensitivity to droloxifene and Adriamycin.