Search

Abstract Background To investigate the diagnostic reliability of selective microdochectomy after direct ductoscopic wire marking of suspect lesions in patients with pathological nipple discharge. Methods Selective microdochectomy due to pathological discharge was performed in 33 patients with mean age of 51.7 years. Ductoscopes of 0.9 and 1.1 mm in diameter with a channel for wire marking were used. Only patients without sonographic or mammographic correlation for the discharge were included. The pathologic mammary duct was wire marked and extirpated under direct visual guidance via the ductoscope. The histological results were compared with cytology, galactography and ductoscopy. Results In 24 out of 33 cases (72%) an intraductal, epithelial proliferation was found histologically. The following sensitivities for intraductal, epithelial proliferations could be determined: cytology 4%, galactography 74%, and ductoscopy 78%. Conclusion The method allows selective microdochectomy of the pathological duct and the intraductal proliferation under visual guidance. The resection volume can be reduced in contrast to the unselective ductectomy after injection of methylene blue.

Background: Population-based estimates of the long-term risk of loco-regional recurrence and distant metastases of breast cancer (BRC) patients are scant, as most published studies used hospital-based cohorts or participants of clinical trials. This work aims to extend available knowledge by providing population-based long-term estimates of the cumulative risk of BRC recurrence up to 10 years after diagnosis., Methods: Data from the population-based Saarland Cancer Registry were used and included 9359 female patients with primary invasive BRC diagnosed between 1999 and 2009. Estimates of the cumulative incidence (CI) of BRC recurrence were derived for patients who had received local surgery with free resection margins by type of recurrence and stratified by age, tumor characteristics and major treatment options, taking into account mortality from any cause as a competing risk., Results: The 10-year CI of BRC recurrence was 16%. For loco-regional recurrence and distant metastases alone it was 8 and 11%, respectively. The estimates showed substantial variation and were particularly increased if tumors were advanced (T1/2N+ 23%, T3/4N0 24%, T3/4N+ 34%), of high grade (23%), or of 'HER2/neu positive' (28%) or 'triple negative' subtype (23%), respectively., Conclusions: The derived estimates reflect the risk of 'real world' patients and may therefore extend available knowledge. These data are thus of great relevance for clinicians, their patients and researchers. The study likewise demonstrated the usefulness of cancer registries for a population-based monitoring of the effectiveness of cancer care in terms of disease recurrence as a major treatment related outcome measure.

Background: An important component of the RAS signalling pathway, the RAS p21 oncogene, is frequently hyperactivated in breast cancer. Its expression in tumor tissue has been linked to poor clinical outcome. This study was designed to evaluate the clinical relevance of RAS p21 levels in peripheral blood in a large cohort of metastatic breast cancer patients., Methods: Two hundred fifty-one patients with metastatic breast cancer were enrolled in this prospective, multicentre, open-label, non-randomized study. Blood samples were collected before start of first-line or later-line treatment. RAS p21 was determined using a sandwich-type ELISA immunoassay. For the determination of the cutoff, blood samples from age-matched healthy controls were analyzed. A value above 452 pg/ml was regarded as elevated (mean + 2 x SD). In the univariate survival analysis, two other cutoffs were considered as well (50th and 75th percentile of patients, i.e. 229 pg/ml and 320 pg/ml). Circulating tumor cells (CTCs) were detected using the CellSearch system., Results: 29 of 251 (12%) patients had RAS p21 levels above the cut-off level of 452 pg/ml. Clinical-pathological parameters, such as hormone receptor and HER2 status, line of therapy and CTC status, did not correlate with RAS p21 levels. Elevated RAS p21 was significantly associated with shorter progression-free and overall survival in the univariate analysis (median PFS: 3.9 months [95%-CI: 1.8-6.0] for patients with elevated RAS p21 levels versus 8.5 months [95%-CI: 7.4-9.5] with non-elevated levels [p = 0.01]; median OS: 7.1 months [95%-CI: 0.3-14.2] versus not reached [p = 0.002], respectively). When RAS p21 cutoffs other than 452 pg/ml were considered, elevated RAS p21 was significantly associated with OS but not with PFS. Classical clinical-pathological factors were included into a multivariate Cox regression analysis. In addition, factors previously shown to influence survival in a univariate analysis, such as serum HER2, CAIX and TIMP1, were included as well. In the multivariate analysis, RAS p21, presence of ≥5 CTCs per 7.5 ml blood, higher grading and higher line of therapy remained independent predictors of shorter OS., Conclusions: Metastatic breast cancer patients with elevated levels of circulating RAS p21 have significantly worse clinical outcome. Hypothetically, these patients might benefit from therapeutic strategies targeting RAS pathway., Trial Registration: Current Controlled Trials ISRCTN59722891 (DETECT); trial registration date: April, 17th 2010; the trial was registered retrospectively.

Background: Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology., Methods: Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers., Results: FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure., Conclusions: Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions.

Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068)., Methods: Patients with primary breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n = 46) between 03/2002 and 12/2004. DTC were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. The change in DTC numbers at 12 months and 24 months versus baseline, as well as patient outcomes were evaluated., Results: 86 patients could be included into survival analysis (median follow-up: 88 months, range: 8-108 mths). Patients in the control group were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%, p = 0.106). 15% of patients in the control group presented with relapse whereas only 8% of ZOL group patients developed metastatic or recurrent disease during follow-up (p = 0.205). At 24 months, 16% of patients from the control group were still DTC positive, whereas all patients treated with ZOL became DTC negative (p = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had significantly shorter overall survival (p = 0.011)., Conclusions: Bisphosphonate therapy contributes to eradication of disseminated tumor cells. The positive influence of bisphosphonates on survival in the adjuvant setting may be due to their effects on DTC., Trial Registration: ClinicalTrials.gov Identifier: NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal Residual Disease in the Bone Marrow (MRD-1)].

Background: The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk., Methods: Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables., Results: The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016)., Conclusions: This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population.