The prognostic and predictive impact of low estrogen receptor expression in early breast cancer: a systematic review and meta-analysis.

INTRODUCTION: Traditionally, estrogen receptor (ER)-positive breast cancer has been defined as tumors with ≥1% positive for ER. The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines recommend that tumors with ER expression of 1%-10% should be classified as ER-low-positive, recognizing the limited clinical evidence on the prognostic and predictive role of low ER expression. We aimed to investigate the predictive role of ER-low expression to neoadjuvant chemotherapy (NeoCT) and the prognostic significance of ER-low expressing breast tumors compared with ER-positive or ER-negative breast tumors. METHODS: A meta-analysis was conducted using the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines and eligible articles were identified on PubMed and ISI Web of Science databases. The primary outcome was pathologic complete response and secondary outcomes were disease-free survival (DFS) and overall survival (OS). Twelve retrospective cohort studies were included in the meta-analysis. NeoCT resulted in higher pathologic complete response among patients with ER-low expression compared with ER-positive and comparable to ER-negative. Patients with ER-low breast cancer had a statistically significant worse DFS and OS compared with patients with ER-positive breast cancer, whereas no difference in DFS or OS was observed between ER-low and ER-negative subgroups. DISCUSSION: The current evidence suggests that ER-low breast cancer has a more similar outcome to ER-negative than to ER-positive breast cancer in terms of DFS and OS. ER-low expression seems also to have a predictive role regarding NeoCT. Considering the certainty of current evidence categorized as low to moderate, our results urge the need for well-designed prospective studies investigating the molecular background and the most appropriate treatment strategy for ER-low expressing breast cancer.

Risk of chemotherapy-induced amenorrhea in patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: The aim of the study was to calculate the rate of chemotherapy-induced amenorrhea (CIA) after treatment with different adjuvant therapies in patients with breast cancer and to evaluate the risk factors for CIA based on the quality of evidence. PATIENT AND METHODS: A search of PubMed and ISI Web of Science was performed. All published trials with female breast cancer patients who received adjuvant chemotherapy and presented data on the rate of CIA were considered eligible. The pooled rates of CIA were calculated by random effects model. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each potential risk factor for CIA by using the generic inverse weighted method. RESULTS: We identified 580 potentially relevant studies, of which 75 were included in the analysis. Among 75 eligible studies, 19 different definitions of CIA have been used. The pooled rate of CIA was 55% (95% CI 50-60%) including 23 673 patients from 74 studies. The rate of CIA was increased by age with an estimate of 26% (95% CI 12-43%), 39% (95% CI 31-58%), and 77% (95% CI 71-83%) for women <35, 35-40, and >40 years old, respectively. Two risk factors were associated with the occurrence of CIA and were supported by strong level of evidence: older age (>40 years old), and the use of tamoxifen. CONCLUSIONS: This meta-analysis summarized the updated evidence on the impact of different adjuvant treatment regimens for breast cancer in menstruation and could serve as a helpful guide for oncologists during the discussion with their patients on fertility issues before decision on adjuvant therapy is made. A uniform definition of CIA is essential in future studies to make the interpretation of results more reliable.

Sentinel lymph node biopsy in patients with microinvasive breast cancer: a systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer. METHODS: We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity. FINDINGS: A total of 24 studies including 968 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.2% (95% Confidence Interval (CI): 2.1%-4.6%), 4.0% (95% CI 2.7%-5.5%), and 2.9% (95% CI: 1.6%-4.6%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate. INTERPRETATION: The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized.

Misoprostol prior to hysteroscopy in premenopausal and post-menopausal women. A systematic review and meta-analysis.

BACKGROUND: Although several randomized controlled trials (RCTs) have examined the effect of misoprostol prior to hysteroscopy for cervical dilatation, no solid conclusion has been reached. We therefore set out to perform a meta-analysis of RCTs. METHODS: We searched MEDLINE, the ISI Web of Science and the Cochrane Library to identify RCTs comparing misoprostol versus placebo or control prior to hysteroscopy. No restrictions on language or time were applied. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for all dichotomous outcomes, whereas mean differences (MDs) and 95% CIs were calculated for continuous outcomes using the Mantel-Haenszel or DerSimonian-Laird model according to the heterogeneity. RESULTS: Of the initial 141 potentially relevant articles that were retrieved, 21 RCTs involving 1786 patients were included in the meta-analysis. Subgroup analyses were performed according to menopausal status and according to whether diagnostic or operative hysteroscopy was performed. Premenopausal women treated with misoprostol had a significantly lower risk for further cervical dilatation in the diagnostic setting [RR (95% CI): 0.56 (0.34-0.92)] and a significantly lower risk for cervical laceration in the operative setting [RR (95% CI): 0.22 (0.09-0.54)], compared with placebo. In contrast, post-menopausal patients did not experience any clear benefit from misoprostol compared with placebo regarding the need for further cervical dilatation [RR (95% CI): 0.99 (0.76-1.30)] and the cervical laceration rate [RR (95% CI): 1.15 (0.40-3.29)]. In addition, the mean cervical width prior to hysteroscopy was significantly higher in premenopausal women treated with misoprostol compared with placebo [MD (95% CI): 2.47 mm (1.81-3.13)] but did not differ among post-menopausal patients [MD (95% CI): 0.39 mm (-0.42 to 1.21)]. CONCLUSIONS: Misoprostol prior to hysteroscopy appears to facilitate an easier and uncomplicated procedure only in premenopausal women.

Local complications of erysipelas: a study of associated risk factors.

BACKGROUND: Local complications of erysipelas include haemorrhagic, bullous, abscessing and necrotic lesions. The risk factors predisposing patients to local complications are not fully known. AIM: To examine local complications of erysipelas and to identify possible risk factors predisposing to their appearance. METHODS: Medical records from all patients hospitalized with complications of erysipelas (purpura, bullae, abscesses and necrosis), admitted to the University Hospital of Heraklion between 1994 and 2002, were retrospectively studied. Clinical and laboratory data were compared with those from patients with erysipelas without local complications. RESULTS: In total, 145 patients were analysed, of whom 46 had local disease complications. Using bivariate analysis, the factors significantly associated with disease complications were found to be age ≥ 51 years, obesity, longer duration of local symptoms, and fever on admission. During hospitalization, increased C-reactive protein level, isolation of pathogens, longer duration of fever and/or presence of leucocytosis, absence of response to initial antibiotic therapy, and longer length of hospitalization were also associated with complications in the bivariate analysis. However, in the multivariate analysis, obesity (OR 4.489, 95% CI 1.719-11.725, P = 0.002) was the only independent factor associated with complicated erysipelas. CONCLUSIONS: This study found obesity to be an independent risk factor for local complications, of erysipelas. Hence, obese patients with erysipelas are prone to complications, and should be carefully evaluated because of the potential severity of disease and the increased risk of failure of empirical antimicrobial therapy.

Evaluating the strength of potential misplaced priorities in opportunistic cancer screening practice in Greece.

PURPOSE: Screening is a significant method for cancer control, nevertheless the implementation of non cost-effective screening tests at national level may constitute a major burden to health economics. The purpose of this study was to determine the cancer screening activities of a large sample of the Hellenic population, in a country with opportunistic screening practice. METHODS: A large survey on cancer screening in Greece was organized and conducted by the Panhellenic Association for Continual Medical Research (PACMeR). Screening performance of evidence-based (EB), non-evidence-based (non EB) and of undefined benefit tests was analysed. RESULTS: 7001 individuals were analysed. Eighty-eight percent of males and 93% of females stated that they were interested in cancer screening practices. Gynecological cancer screening was performed in the range of 23-38%. Colorectal cancer screening was rarely performed in both genders (1- 2%), while non-evidence-based tests were regularly performed (urinalysis 50% and chest radiography 15-18%). Full blood count and PSA measurement were widely accepted (over 45% in both genders and 19.5% in males, respectively). Sociodemographic characteristics did not influence the performance of EB tests in males while females' activities were highly influenced by such parameters. CONCLUSION: Opportunistic cancer screening in a primary health care system where national guidelines are missing may cause ambiguous results. Reconsideration of health policy in such cases is mandatory.

Bevacizumab in metastatic breast cancer: a meta-analysis of randomized controlled trials.

Numerous studies have demonstrated that angiogenesis and in particular VEGF over-expression play an essential role in the progression and metastatic potential of breast cancer. Bevacizumab is a humanized recombinant monoclonal antibody that specifically blocks the binding of VEGF to high-affinity receptors and it has been recently used for the treatment of metastatic breast cancer. We conducted a meta-analysis to synthesize available evidence for use of bevacizumab in metastatic breast cancer patients. Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, progression free survival (PFS) and objective response rate (ORR). Five trials were identified with 3,163 eligible patients. Combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in PFS (HR = 0.70, 95% CI 0.60-0.82, P = 9.3 x 10(-6)) and ORR (RR = 1.26, 95% CI 1.17-1.37, P = 9.96 x 10(-9)) compared with chemotherapy alone. Differences in objective response rates were substantial independently by the type of chemotherapy used, while PFS advantages were observed only for taxanes. The pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (HR = 0.90, 95% CI 0.80-1.03, P = 0.119). This meta-analysis shows that the addition of bevacizumab to chemotherapy offers meaningful improvement in PFS and ORR in patients with metastatic breast cancer. Bevacizumab treatment might be suggested for treatment of 1st line metastatic breast cancer, but more data are needed until statistical overall survival differences will be documented and firm guideline recommendation could be given.

Screening practice and misplaced priorities

PURPOSE: To estimate cancer screening coverage among a large sample of Greek individuals. METHODS: 7012 adults from 30 Hellenic areas were surveyed. Tests included: faecal occult blood test, sigmoidoscopy,chest X-ray, urine test, testicular examination,trans-rectal ultrasound, full blood count, skin examination,digital rectal examination, PSA, Pap test, mammography,clinical breast examination (CBE), self breast examination and breast ultrasound. RESULTS: Eighty-eight percent of males and 93% of females declared being interested in cancer screening; 37.8% of men and 37.9% of women had had a medical consultation for screening purpose in the previous 2 years. Less than 2%reported having received screening for colorectal cancer or skin malignancies. Screening for cervical cancer, mammography and CBE was reported by 39.6%, 22.8% and 27.9% of females respectively. Twenty percent of males reported screening for prostate cancer. CONCLUSION: The actual opportunistic screening approach presents important deficiencies with displaced priorities in test performance and a low proportion of individuals undergoing recommended tests (AU)

Tyrosine kinase inhibitors in treatment of fibrous histiocytoma.

AIM: To describe potential beneficial effects of tyrosine kinase inhibitor in the treatment of unresectable/metastatic fibrous histiocytoma. METHODS: We report a case of advanced stage fibrous histiocytoma with locally recurrent disease plus lung and bone metastatic deposits. Patient was treated with the tyrosine kinase inhibitor sunitinib. RESULTS: Treatment with Sunitinib resulted in disease stabilization in the regional lesion and in good partial response for metastatic foci (reduction in number and size). After 13 months of treatment the patient is doing well with no tumor progression. CONCLUSIONS: This case appears to be one of the first documentations of beneficial effect and potential long-term benefit of TKIs in the treatment of fibrous histiocytoma.

Responsibilities in cancer preventive care in Greece. A physicians' survey

BACKGROUND: Colorectal cancer is the second leading cause of cancer death in European countries. Differences in screening implementation may explain USA vs. European survival differences. The proportion of European primary care physicians advising colorectal screening has been reported to be inconsistent. We therefore hypothesised the presence of a belief-related bias among European physicians regarding who is responsible for cancer screening delivery. OBJECTIVES: To index beliefs in cancer screening implementation among a wide sample of Greek physicians. Study design Cross-sectional survey. METHODS: Three hundred and sixty-six physicians involved in primary care activities in 15 provinces answered a questionnaire about responsibility in cancer screening delivery. Results 22.4% and 7.6% of physicians declared that the health system and the patients, respectively, have the main responsibility for cancer screening implementation, while 70 % advocated patient-health system co-responsibility. Beliefs were statistically correlated to age (p=0.039) and specialisation category (p=0.002). Patients' will was mainly indicated by internists, trainee internists and physicians older than 30, while GPs, trainee GPs and house officers were mainly health system-oriented. Worryingly, when physicians were asked about which specialty should inform the population, 81% indicated family doctor (for-fee-service) while the involvement of free-from-fee specialities was inconsistent. CONCLUSION: A considerable disorientation about responsibilities in cancer screening delivery was observed in our study sample. Continual medical education and clear redefinition of primary care physicians' activities are required (AU)

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