Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties.

Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.

STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression.

Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.

MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis.

Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5ß1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5ß1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.

Distant metastasis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) relapses more frequently than hormone receptor-positive subtypes and is often associated with poor outcomes. This retrospective study reviewed the pattern of distant metastasis with regard to survival in patients with TNBC. A total of 205 TNBC patients were analyzed. TNBC patients with lung metastases had the longest median post-metastatic OS (with 95% confidence interval) of 16.6 (10.3-22.9) months, followed by the bone, 16.3 (11.7-20.8) months, the liver, 8.9 (3.5-14.4) months, the pleura, 7.5 (2.8-12.3) months, and the brain, 4.3 (0.6-8.0) months. Kaplan-Meier plots indicated that TNBC patients with metastatic spread to brain, liver, and pleural had poorer post-metastatic OS rate than patients with lung metastases (p = 0.001, 0.004, and 0.029, respectively). Moreover, brain and liver metastases correlated significantly with poorer post-metastatic OS as compared to bone metastasis (p = 0.004 and 0.011, respectively). Route of first metastasis correlated significantly with survival of TNBC patients with brain metastases being the poorest survival indicator, followed by metastases to liver, pleura, bone, and lung.

Breast tumor-associated osteoblast-derived CXCL5 increases cancer progression by ERK/MSK1/Elk-1/snail signaling pathway.

The skeleton is the most common metastatic site for breast cancer, with bone metastasis causing pain as well as risk of pathological fractures. Interaction between tumors and the bone microenvironment creates a vicious cycle that accelerates both bone destruction and cancer progression. This study is the first to analyze the soluble factors secreted by breast tumor-associated osteoblasts (TAOBs), which are responsible for promoting cancer progression. The addition of CXCL5 (chemokine (C-X-C motif) ligand 5), present in large amounts in TAOB-condition medium (TAOB-CM), mimicked the inductive effect of TAOB-CM on breast cancer epithelial-mesenchymal transition, migration and invasion. In contrast, inhibition of CXCL5 in OBs decreased TAOB-mediated cancer progression. Inducement of MCF-7 and MDA-MB-231 cancer progression by TAOB-derived CXCL5 is associated with increased Raf/MEK/ERK activation, and mitogen- and stress-activated protein kinase 1 (MSK1) and Elk-1 phosphorylation, as well as Snail upregulation. Activation of Elk-1 facilitates recruitment of phosphorylated MSK1, which in turn enhances histone H3 acetylation and phosphorylation (serine 10) of Snail promoter, resulting in Snail enhancement and E-cadherin downregulation. Moreover, mice treated with anti-CXCL5 antibodies showed decreased metastasis of 4T1 breast cancer cells. Our study suggests that inhibition of CXCL5-mediated ERK/Snail signaling is an attractive therapeutic target for treating metastases in breast cancer patients.

Prospective analysis of KRAS wild-type patients with metastatic colorectal cancer using cetuximab plus FOLFIRI or FOLFOX4 treatment regimens.

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has proven to be efficient in the treatment of metastatic colorectal cancer. We made a prospective study of the efficacy and toxicities of cetuximab-combination first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had been identified by direct sequencing. Associations between clinical response/progression-free survival/overall survival/toxicities and cetuximab-combination chemotherapy timing were evaluated. The overall response rate was significantly higher for first-line treatment than for second/third-line treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both progression-free survival and overall survival indicated significantly longer survival of first-line treatment than second/third-line treatment patients. This study is a validation of a molecular analysis of KRAS wild-type status for the prediction of response to cetuximab-combination chemotherapy for metastatic colorectal cancer patients; its predictive role was less prominent in the second/third-line than in the first-line treatment patients.

Two-year quality of life after breast cancer surgery: a comparison of three surgical procedures.

PURPOSE: To analyze longitudinal changes in each subscale of a quality of life (QOL) measure and to explore their relationships to effective QOL predictors in breast cancer surgery patients. PATIENTS AND METHODS: This prospective study analyzed 172 patients at two tertiary academic hospitals. All patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its supplementary breast cancer measure (QLQ-BR23) at baseline and at 1 and 2 years postoperatively. The 95% confidence intervals for differences in responsiveness estimates were derived by bootstrap estimation. Scores derived by these instruments were interpreted by generalized estimating equation (GEE) before and after surgery. RESULTS: A 2-year follow-up survey of the examined population revealed significant (P < 0.05) improvement in each QOL subscale. In both postoperative surveys, effect size was largest in the QLQ subscales for patients who had received mastectomy with reconstruction and lowest in those who had received modified radical mastectomy. After adjusting for time effects and baseline predictors, GEE approaches revealed the following explanatory variables for QOL: time, type of surgical procedure, age, chemotherapy, radiotherapy, hormone therapy, and preoperative functional status. CONCLUSIONS: When evaluating QOL after breast cancer surgery, several factors other than the surgery itself should be considered. Patients should also be advised that their postoperative QOL might depend not only on the success of their operations, but also on their preoperative functional status.

Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: prognostic significance of detection for early relapse.

BACKGROUND: The purpose of this study was to detect postoperative persistent circulating tumour cells (CTCs) in stages II and III colon cancer patients undergoing curative resection and so identify a subgroup of patients who are at high risk for early relapse. METHODS: Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in 141 stages II and III colon cancer patients undergoing curative resection to determine the significance of CTCs in postoperative early relapse. RESULTS: Out of 141 patients, postoperative early relapse and non-early relapse/no relapse was found in 48 (34.0%) patients and 93 (66.0%) patients, respectively. Univariately, postoperative early relapse was significantly correlated with lymph node metastasis (P=0.025), vascular invasion (P=0.002), perineural invasion (P=0.001), laparoscopic surgery (P=0.019), high postoperative serum CEA levels (P=0.001), and presence of persistent postoperative CTCs (P<0.001). Using a multivariate proportional hazards regression analysis, the presence of perineural invasion (P=0.034; HR, 1.974; 95% CI: 1.290-3.861), high postoperative serum CEA levels (P=0.020; HR, 2.377; 95% CI: 1.273-4.255), and the presence of persistent postoperative CTCs (P<0.001; HR, 11.035; 95% CI: 4.396-32.190), were demonstrated to be independent predictors for postoperative early relapse. Furthermore, the presence of persistent postoperative CTCs was strongly correlated with a poorer disease-free and overall survival (both P<0.001). CONCLUSIONS: This study suggests that molecular detection of persistent postoperative CTCs is a prognostic predictor of early relapse in UICC stage II/III colon cancer patients, and thus could help to define patients with this tumour entity for an enhanced follow-up and therapeutic program.

Uterine leiomyosarcoma metastasis to the breast.

BACKGROUND: Uterine leiomyosarcoma is a rare female neoplasm with a high recurrent and metastatic rate. However, only a few cases have been reported on metastasis to the breast. The purpose of this work is to stress the role of follow-up and to increase physicians' awareness of such lesion. case: A 62-year-old female suffered from a breast nodule and multiple metastases six years after resection for uterine leiomyosarcoma. Pathology revealed a rare condition of uterine leiomyosarcoma with breast metastasis. CONCLUSION: The case highlights the important role of long-term follow-up in uterine leiomyosarcoma and implies the necessity of tissue proof in patients with the disease.

Altered p-JAK1 expression is associated with estrogen receptor status in breast infiltrating ductal carcinoma.

The mammalian Janus kinase (JAK) family consists of four members, namely JAK1, JAK2, JAK3 and TYK2, which play a critical role in cytokine/growth factor signaling and is increasingly associated with human cancers. Aberrant activation of these non-receptor tyrosine kinases may contribute to carcinogenesis. Herein, we focused on exploring the potential role of p-JAK1 in breast cancer. The expression profiles of p-JAK1 were analyzed in 68 pairs of cancer and non-cancer breast tissues from the same infiltrating ductal carcinoma case by using immunoblotting technique. The results obtained were further correlated with clinicopathological characteristics. Intriguingly, p-JAK1 expression was decreased in 55.9% of breast cancer tissues as compared to the matched non-cancer tissues. Further immunohistochemistry study showed an intense p-JAK1 staining predominantly in adjacent normal breast tissues but not the matched cancer lesions. Decreased p-JAK1 expression in breast cancer tissues was significantly correlated with positive estrogen receptor (ER) status and increased tumor size (p=0.010 and 0.009). We also found that p-JAK1 expression was high in ERalpha-negative breast cancer cell lines but was low in ERalpha-positive breast cell lines. Transfection of ERalpha-positive MCF-7 cells with an ERalpha-specific siRNA upregulated the expression of p-JAK1. In summary, our results indicated that an altered p-JAK1 expression might be involved in the development of breast infiltrating ductal carcinoma in an ERalpha-related manner.

Expression of CXCR4 is associated with axillary lymph node status in patients with early breast cancer.

Recent studies have discovered that CXCR4 is associated with tumor metastasis. It is worth understanding the association between CXCR4 expression and axillary lymph node involvement in early breast cancer. Eighty-five patients with early breast cancers were divided into three groups based on their axillary lymph node status. CXCR4 expression was assessed by immunohistochemistry in all cases and its correlation with axillary lymph node involvement was evaluated. There was a significant difference in nuclear CXCR4 expression among these three groups and high nuclear expression of CXCR4 was associated with cases with no lymph node involvement. However, high cytoplasmic expression of CXCR4 was associated with patients who developed high-level axillary lymph node involvement. In conclusion, the different staining locations of CXCR4 have varying biological significance for the metastatic potential of axillary lymph nodes. In particular, it provided information that high cytoplasmic expression of CXCR4 was related to axillary internodal metastasis, and adjuvant radio-chemotherapy was suggested.

Enhanced photocatalytic degradation of VOCs using Ln3+-TiO2 catalysts for indoor air purification.

Two types of lanthanide ion-doped titanium dioxide (Ln3+-TiO2) catalysts including La3+-TiO2 and Nd3+-TiO2 were prepared by a sol-gel method. The effects of the lanthanide ion doping on the crystal structure, surface area, adsorption properties, pore size distribution, and surface chemical state of the catalysts were investigated by means of XRD, BET, and XPS. As results, the crystal size decreased significantly, while the specific surface area, t-plot total surface area, micropore volume, and the total pore volume increased owing to the lanthanide ion doping. The nitrogen adsorption-desorption isotherms of the catalysts showed that the N2 adsorption ability of the Ln3+-TiO2 catalysts was better than the TiO2 catalyst. Among them, the 0.7% Ln3+-TiO2 catalysts demonstrated the highest adsorption ability. The photocatalytic activity of the catalysts was investigated in the experiments of the photocatalytic degradation of benzene, toluene, ethylbenzene and o-xylene (BTEX) in a gaseous phase. The photocatalytic efficiency of the TiO2 catalysts with the lanthanide ion doping was remarkably enhanced by BTEX removal. The 1.2% Ln3+-TiO2 catalysts achieved the highest photocatalytic activity. The enhanced photodegradation of BTEX is possibly due to the improved adsorption ability and the enhanced electron-hole pairs separation due to the presence of Ti3+ on the surface of Ln3+-TiO2 catalysts and the electron transfer between the conduction band/defect level and lanthanide crystal field state.

Arsenite-induced nitric oxide generation is cell cycle-dependent and aberrant in NBS cells.

Exposure to arsenic has been reported to cause DNA damage and eventually the occurrence of bladder, lung and skin cancers. A previous report has demonstrated that arsenite-induced phosphorylation of Mre11, a protein involved in the repair of DNA double strand breaks (DSBs), is M phase-dependent and requires the Nijmegen breakage syndrome (NBS) protein, NBS1 [DNA Repair 1 (2002) 137]. Furthermore, arsenite treatment arrests cells at the M phase and the cells eventually go through apoptosis [Biochemical Pharmacology 60 (2000) 771]. Here we demonstrate that arsenite treatment enhances the generation of nitric oxide (NO), and that the enhanced NO generation is dominant at the G2/M phase. Arsenite-induced NO generation is impaired in DSB repair-defective NBS cells, but not in NBS1-reconstituted NBS cells, suggesting NBS1 is required for effective NO generation. In summary, our study showed, for the first time, that arsenite-induced NO generation is cell-cycle- and NBS1-dependent.

Primary abscess of the omentum: report of a case and review of the literature.

Primary abscess of the omentum is an infrequent disease entity. We report a case of 60-year-old male patient who suffered from left lower quadrant abdominal pain with localized abdominal wall tenderness, nausea and high-grade fever for the previous few days. Computerized tomography scan revealed a heterogeneous lesion that adhered to the abdominal wall. A pre-operative diagnosis of colonic diverticulitis complicated with intra-abdominal abscess was made and a laparotomy was done. At surgical exploration, an indurate mass consisting of abscess within the omentum was identified. The surgical procedure consisted of resection of the omental abscess with abdominal wall debridement, and subsequent antimicrobial therapy was administered. Postoperatively, the patient recovered uneventfully. Clinicians who treated such patients should be aware of this problem because of the difficulty of preoperative diagnosis.

The diagnostic value of galactography in patients with nipple discharge.

To evaluate preoperative galactographic findings in the differentiation between the benign and malignant lesions in patients presenting spontaneous nipple discharge without mass. Of the 215 patients who have undergone the galactography, 181 cases with abnormal galactography had surgery performed. All galactrograms were reviewed and galactographic findings were correlated to the pathological results to determine diagnostic differentiation. Of the 181 cases we operated on, 112 cases were macroscopically bloody, with 30 cases having cancers (26.8%). Fifty-four cases with serous discharge had seven cancer cases (13.0%). No cancer cases with other color discharge were found. Of the 37 cancer cases, 11 cases had lesions located in the main mammary ducts (lactiferous duct and the segmental duct) (29.7%) and 26 cases had lesions in the peripheral ducts (the subsegmental duct and its branches) (70.3%) (P<.05). Of 113 cases with benign proliferative ductal lesions, 88 cases were located in the main mammary duct (77.9%) and 25 cases in the peripheral mammary duct (22.1%) (P<.05). Otherwise, 29 cancer cases (82.9%) had ductal obstructions and 28 cancer cases (75.7%) had irregular intraductal defects that appeared in the galactograms, which is different from the 113 benign proliferative ductal lesion cases that had 88 cases (71.7%) with ductal dilatation and 90 cases (79.6%) with lobular or smooth intraductal defects (P<.05). These results showed that the cancer cases had a higher rate of locating in the peripheral duct, irregular intraductal duct defects, and ductal obstruction, and a lower rate associated with ductal dilatation or torsion. The galactographic findings were evaluated using the tumor location, types of intraductal defects, ductal obstruction, and dilatation. Preoperative diagnostic galactography is useful in differentiating between the benign or malignant lesions in patients with spontaneous nipple discharge.

Expression of HER-2/NEU oncoprotein in familial and non-familial breast cancer.

The HER-2/neu proto-oncogene amplification or oncoprotein overexpression is an important prognostic factor and a predictive factor for resistance to endocrine therapy and adjuvant chemotherapy in breast cancers. Moreover, it is an entry criterion in the assessment of patients for whom Herceptin (Trastuzumab) treatment is considered. The overexpression rate of HER-2/neu oncoprotein has been identified in 10% to 40% of human breast cancers. In Taiwan, a higher grade of pathobiologic characteristics of familial breast cancer was also noted than that found in the non-familial group. It is worthwhile to evaluate whether the overexpression is more frequent in familial breast cancers. Fifty-six familial and 111 non-familial breast cancers were studied between 1990 and 1999 to assess both the overexpression of HER-2/neu oncoprotein immunohistochemically and the correlation with the histological type, grade and stage of breast carcinoma. The overexpression rate is higher in the familial breast cancer group (50.0%) when compared with non-familial breast cancer group (36.9%), which did not prove to be statistically significant (P = 0.1068). However, when the infiltrating ductal carcinomas of both groups are compared, it is statistically significant (52.3% vs. 33.7%, P = 0.0429). Overexpression correlated with node status and histological grade of infiltrating ductal carcinomas in non-familial and overall breast cancers. It also correlated with nuclear pleomorphism and mitotic counts, but not tubule formation or tumor size. All 3 cases of Paget's disease revealed overexpression, whereas all 12 cases of mucinous and one case of metaplastic carcinoma and one case of medullary carcinoma were negative. The overexpression rate was higher both in familial and non-familial intraductal carcinomas (57.1% vs. 73.3%, P = 0.4716). No statistical difference was identified between the 2 subsets. A case of infiltrating ductal carcinoma combined with intraductal carcinoma revealed heterogeneous staining in the component of ductal carcinoma in situ, while the invasive component did not. This suggests that overexpression decreases within individual tumors as they evolve from in situ to invasive lesioins. The HER-2/neu may imply a different role in intraductal carcinoma, Paget's disease and invasive duct carcinoma. Although the overexpression rate of HER-2/neu oncoprotein of familial breast cancer was not significantly higher than that of the non-familial group, it is appropriate to evaluate the rate of HER-2/neu overexpression according to the histological type of breast cancers from familial breast cancer and non-familial breast cancer. The prognoses will be needed for future evaluation.

Measurement of the volume of the pedicled TRAM flap in immediate breast reconstruction.

The transverse rectus abdominis musculocutaneous (TRAM) flap is now accepted as the standard for breast reconstruction, but achieving symmetrical breast reconstruction is still a challenge. A precise estimate of the volume of the flap is necessary to reconstruct a symmetrical and aesthetically pleasing breast. Many methods have been developed to overcome this problem, but they have not been suitable for the pedicled TRAM flap. By using a self-made device based on the Archimedes' principle, the authors can calculate accurately the volume of the pedicled TRAM flap and predict reliably the breast volume intraoperatively. The "procedure" is based on a self-made box into which the pedicled TRAM flap is placed. Warm saline is added to the box and the flap is then removed. Flap volume is calculated easily by determining the difference between the preestimated volume of the box and the volume of the residual water. From February to May 2000, this method was used on 28 patients to predict breast volume for breast reconstruction. This study revealed that the difference of the maximal chest circumferences (the index of the breast volume) demonstrates a positive correlation with the difference of the volumes and weights between the mastectomy specimen and the net TRAM flap. However, a more closely positive correlation exists between the differences of maximal chest circumference volume (r = 0.677) than maximal chest circumference weight (r = 0.618). These data reveal that the reconstructed breast's volume has a closer relationship with the volume of the net pedicled TRAM flap, rather than with its weight.

Familial breast cancer in southern Taiwan.

The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non-familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease-free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed.

Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

Biochemical markers for assessment of bone metastases in patients with breast cancer.

Breast cancer commonly metastasizes to bones, producing both osteolytic and osteoblastic deposits. Different markers for quantitative determination of bone turnover have been developed to evaluate bone metastases of breast cancer. The urinary deoxypyridinoline (Dpd), a crosslink product of collagen molecules found in bone and excreted in urine during bone degradation, and bone specific alkaline phosphatase (B-ALP), an isoenzyme localized in the membrane of osteoblasts and released in circulation during bone formation, were recently described as a group of markers of bone turnover in metastatic cancer. The urinary Dpd/creatinine (Cre) ratios and the serum B-ALP activity were determined in the samples from 148 patients who suffered from breast cancer (BC patients) with or without bone metastases, and 42 healthy women. For comparison, other biochemical markers, e.g. carcinoembryonic antigen (CEA), CA15-3, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPSA), and total alkaline phosphatase (T-ALP) in these samples were also evaluated. The results showed that there was a significant difference in urinary Dpd/Cre ratio between the control group and the patients with breast cancer (BC group) (mean +/- S.D., 5.69 +/- 1.26 vs. 8.19 +/- 3.95 nM/mM, P < 0.05). However, there was no significant difference between their B-ALP activities in the two groups. In addition, the BC patients with bone metastases showed elevated urinary Dpd/Cre ratios and B-ALP activities and ratios of (Dpd/Cre)/B-ALP in compare with BC patients without bone metastases (P < 0.05). Meanwhile, the urinary Dpd/Cre ratios (10.50 +/- 5.04 nmol/mmol) in the advanced stage of BC patients were higher than those in an early stage (7.45 +/- 3.23 nmol/mmol) (P < 0.05), but their serum B-ALP activities increased only in stage IV (P < 0.05). The urinary Dpd/Cre ratios also increased progressively according to the degree of bone metastases (P < 0.05), but their serum B-ALP activities only increased in severe bone metastases (P < 0.05). The results showed that the increase of a bone osteolytic activity took place earlier than that of a bone osteoblastic activity in the metastatic BC patients. In compare with other conventional markers, the best diagnostic efficiency of biochemical markers, analyzed by step wise discriminate analysis, was provided by CEA followed by Dpd/Cre ratio, CA15-3, TPA, TPSA, B-ALP and T-ALP. We conclude that showed the urinary Dpd/Cre ratio was a useful tumor marker to evaluate breast cancer with bone metastases.