Serum tumor markers in breast cancer: are they of clinical value?

BACKGROUND: Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA. METHODS: The literature relevant to serum tumor markers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. RESULTS: Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associated with adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot be evaluated by use of conventional criteria. CONCLUSIONS: CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer that is not assessable by existing clinical or radiologic procedures.     

Following breast cancer surgery, which treatments are necessary?

This essay received first prize in the Third Nursing Conferences organized by the Sanitary Consortium of the Alt Penedés County in Catalonia. In a very clear, simple way, this essay deals with those questions which most concern women who have undergone an axillary extirpation. The authors describe their everyday experiences in health education for women who have undergone this surgery.     

Biomarkers of sepsis: clinically useful?

PURPOSE OF REVIEW: The purpose of this review is to indicate recent developments in biomarkers of sepsis and to evaluate their impact on clinical use. According to the 'surviving sepsis campaign,' diagnosis of sepsis and infection is urgent; early and specific treatment is most effective to reduce complications and to decrease mortality. RECENT FINDINGS: A variety of biomarkers of sepsis is presently available. The diagnostic spectrum of the various markers, however, is different. Some primarily indicate severity of inflammation (e.g. interleukin-6), others respond to infection, but do not indicate the host response well (endotoxin, lipoprotein binding protein, triggering receptor on myeloid cells). There are new markers with limited clinical experience, for example triggering receptor on myeloid cells or mid-pro atrial natriuretic peptide (Seristra, Brahms AG, Hennigsdorf, Germany). Procalcitonin is a well-established biomarker of sepsis that fulfills several criteria of clinical needs: it responds both to infection and severity of inflammation and thus has an impact on therapy. Recent studies indicate that antibiotic treatment can also be guided by procalcitonin. Further indications, including diagnosis of invasive bacterial infections and diagnosis of sepsis in neonates and children have been reported recently. SUMMARY: Recent data and cumulative analyses indicate that biomarkers of sepsis improve diagnosis of sepsis. However, only a few markers have impact on therapy and fulfill the clinical requirements. Procalcitonin is a well-established marker, indicating infection, sepsis, and progression to the more severe stages of the disease. Today, this biomarker should be in the diagnostic portfolio of an intensive care unit or emergency ward.     

Differentiation of nonalcoholic from alcoholic steatohepatitis: are routine laboratory markers useful?

BACKGROUND/AIMS: Specific markers for differentiation of nonalcoholic (NASH) from alcoholic steatohepatitis (ASH) are lacking. We investigated the role of routine laboratory parameters in distinguishing NASH from ASH. METHODS: Liver biopsies performed at our hospital over a 10-year period were reviewed, 95 patients with steatohepatitis identified and their data prior to biopsy reevaluated. The diagnosis NASH or ASH was assigned (other liver diseases excluded) on the basis of the biopsy and history of alcohol consumption (< 140 g/week). Logistic regression models were used for analysis. RESULTS: NASH was diagnosed in 58 patients (61%; 30 f) and ASH in 37 (39%; 9 f). High-grade fibrosis (59% vs. 19%, P < 0.0001) and an AST/ALT ratio > 1 (54.1% vs 20.7%, P = 0.0008) were more common in ASH. The MCV was elevated in 53% of ASH patients and normal in all NASH patients (P < 0.0001). Multivariate analysis identified the MCV (P = 0.0013), the AST/ALT ratio (P = 0.011) and sex (P = 0.0029) as relevant regressors (aROC = 0.92). The AST/ALT ratio (P < 0.0001) and age (P = 0.00049) were independent predictors of high-grade fibrosis. Differences in MCV were more marked in high-grade fibrosis. CONCLUSIONS: Higher MCVs and AST/ALT ratios in ASH reflect the severity of underlying liver disease and do not differentiate NASH from ASH. Instead, these biomarkers might prove useful in guiding selection of patients for liver biopsy and in targeting therapy.     

Soy isoflavones: are they useful in menopause?

In October 1999, the US Food and Drug Administration authorized the use on food labels of health claims associated with soy protein and the reduced risk of coronary heart disease. Several studies have indicated that a total daily intake of 25 g of soy protein paired with a low-fat diet resulted in clinically important reductions of total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Soybeans are a rich source of isoflavones, a class of phytoestrogens found predominantly in legumes and beans. Soy isoflavones are heterocyclic phenols with structural similarity to estradiol-17beta and selective estrogen receptor modulators. Actions at the cellular level depend on the target tissue, receptor status of the tissue, and the level of endogenous estrogen. Studies of soy-based diets evaluating the relation between soy consumption and serum lipid concentrations revealed that soy consumption significantly decreased total cholesterol, LDL cholesterol, and triglyceride levels. However, the soy isoflavones do not increase high-density lipoprotein cholesterol or triglyceride levels. The effects of soy protein on other target tissues reflect estrogenlike agonist and antagonist effects. Epidemiological studies suggest a protective effect of soy protein on breast tissue as evidenced by the lower rates of breast cancer in East Asian countries where soy is a predominant part of the diet. Data available from human studies on the effect of isoflavones on osteoporosis are limited, and additional studies are needed to support a role in osteoporosis prevention. Thus far, there is no evidence for a stimulatory effect of isoflavones on the endometrium. A few studies reveal a minimal effect of soy on hot flashes, with soy reducing hot flashes 45% and placebo causing a 30% reduction compared with an approximate 70% reduction in hot flashes with estrogen replacement therapy. Evidence from laboratory studies reveals neither a positive nor a negative effect of soy isoflavones on cognition. To date, no adverse effects of short- or long-term use of soy proteins are known in humans. The only adverse effects known are those reported in animals (infertility in sheep and quails grazing on phytoestrogen-rich pastures). In conclusion, soy isoflavones are biologically active compounds. Current data are insufficient to draw definitive conclusions regarding the use of isoflavones as an alternative to estrogen for hormone replacement in postmenopausal women. Although epidemiological and basic laboratory studies allude to the possible protective effects of soy isoflavones at specific target tissues, randomized, placebo-controlled clinical trials are necessary to address these important issues.     

Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers worldwide. Its main application is mostly in gastrointestinal cancers, especially in colorectal malignancy. Although in use for almost 30 years, the clinical value of CEA in colorectal cancer is still not clear. METHODS: The literature relevant to the clinical value of CEA in colorectal cancer was reviewed. Particular attention was paid to studies involving metaanalyses and guidelines issued by Expert Panels. RESULTS: Although of little use in detecting early colorectal cancer, high preoperative concentrations of CEA correlate with adverse prognosis. Serial CEA measurements can detect recurrent colorectal cancer with a sensitivity of approximately 80%, a specificity of approximately 70%, and can provide a lead time of approximately 5 months. CEA is the most frequent indicator of recurrence in asymptomatic patients and currently is the most cost-effective test for the preclinical detection of resectable disease. CEA is most useful for the early detection of liver metastasis in patients with diagnosed colorectal cancer. Overall, however, little evidence is available that monitoring of all patients with diagnosed colorectal cancer leads to enhanced patient outcome or quality of life. CONCLUSIONS: Currently, the most useful application of CEA is in the detection of liver metastasis from colorectal cancers. Because of the relative success of surgery in resecting hepatic metastases, serial determinations of the marker are recommended for detecting cancer spread to the liver. In the future, preoperative concentrations of CEA may be included with the standard staging procedures for assessing prognosis.     

Precursors to pre-eclampsia: are there markers in the fetal circulation?

One of the fundamental issues in pre-eclampsia (hypertension in pregnancy) research is to find serum proteins that can act as markers of disease predisposition, remote disease onset, imminent disease onset or disease activity at the height of its destructive powers. We make assumptions, not infrequently, that positive findings at the time of delivery reflect early changes in the maternal and fetal circulations. Very little has been defined in terms of fetal circulation, as it is, by and large, deemed to be harder to access and less likely to lend itself to useful non-invasive diagnostic tests in early pregnancy. The study published in this issue of Clinical Science by Prickett et al. shows that there is a differential expression of the precursor molecule of CNP (C-type natriuretic peptide), N-terminal proCNP, in pre-eclampsia. At term, pre-eclamptic umbilical cord plasma concentrations are decreased relative to normal pregnancy, possibly reflecting a decrease in placental production. At the same time maternal levels are increased relative to normal pregnancies and this possibly reflects an increase in myometrial/endovascular production. There is no doubt that the predominant actions of these hormones are local and whether plasma levels are a true reflection of dynamic changes in local production and effect is yet to be seen. This study represents a promising start in identifying large stable molecules which could be markers for pre-eclampsia. This study has relatively small numbers of patients and work still needs to be done to determine the utility of umbilical cord levels in early phases of the disease. Whether serum levels of N-terminal proCNP can provide an accurate reflection of normal or pathological maternal uterine adaptation to pregnancy remains a question worth evaluating.     

Adjuvant therapy for HER2 positive breast cancer: are anthracyclines still necessary?

Anthracyclines are integral components of most adjuvant chemotherapy regimens for surgically removed early breast cancer and are central to the accepted treatment standards. Recently the standard anthracycline regimen of doxorubicin plus cyclophosphamide was found to be inferior in preventing recurrence of breast cancer when compared to cyclophosphamide and docetaxel, questioning the necessity to expose patients to the potential cardiotoxicity of anthracycline in the adjuvant setting. Trastuzumab, a humanized monoclonal antibody against the extracellular domain of the human epidermal growth factor receptor 2 (HER2) has become the cornerstone of treatment of breast cancers that overexpress HER2 in the neo-adjuvant and metastatic setting. Unfortunately, the combination of anthracyclines and trastuzumab produces a high incidence of cardiotoxicity as seen in early trials of metastatic breast cancer. Five adjuvant trials combining trastuzumab with different anthracycline-based regimens have been reported, all of them revealing similar efficacy in reducing recurrence of breast cancer. The trastuzumab adjuvant trial 006 from the Breast Cancer International Research Group shows for the first time that a nonanthracycline-containing regimen with trastuzumab has equivalent efficacy in decreasing the recurrence of breast cancer, with less incidence of cardiotoxicity when compared to anthracycline-containing trastuzumab adjuvant regimens. Further trials are needed to determine the optimal length of adjuvant therapy with trastuzumab, as well as long-term side effects with special attention to cardiotoxicity.     

Is meta-analysis clinically useful for perianesthesia nurses?

Meta-analyses can provide clinicians with the evidence-based information necessary to effect change in patient care delivery. Meta-analysis, the application of statistical techniques to condense data from a group of individual studies, is the most sophisticated summary of research evidence. An example meta-analysis study of inadvertent surgical hypothermia is used in this article to describe how nurses can locate, evaluate, and apply synthesized research data for perianesthesia clinical practice. Without data to support decisions, nurses will increasingly be faced with decisions made by others based on cost-cutting measures alone. Although meta-analysis may resolve a controversy or solve a clinical problem, it will not provide simple statistical answers for complex problems or obviate the need for sound and compassionate clinical judgment.