Maximilian Klar

The MSKCC nomogram for prediction the likelihood of non-sentinel node involvement in a German breast cancer population.

Objective To assess whether the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for prediction of NSLN metastasis is useful in a German breast cancer population and whether the characteristics of the breast tumor and the sentinel lymph node (SLN) are able to predict the likelihood of non-sentinel lymph node (NSLN) metastasis. Methods A total of 545 patients with primary breast cancer and SLN examination were evaluated. The MSKCC nomogram was applied to 98 patients with a positive SLN who subsequently had completion axillary lymph node dissection (ALND). Predictive accuracy was assessed by calculating the area under the receiver-operator characteristic (ROC) curve. The collective was evaluated by correlating the prevalence of NSLN and SLN metastasis to pathological features. Results The MSKCC nomogram achieved a ROC of 0.58 indicating a bad accuracy of the nomogram. Tumor size, histology, lymphovascular infiltration, multifocality, Her-2-neu positivity, and nuclear grade correlated with the probability of SLN metastasis. Histology and primary tumor localization correlated significantly with the probability of NSLN metastasis. Conclusions The MSKCC nomogram did not provide a reliable predictive model in our study population. However, the likelihood of SLN metastasis correlated with the presumed risk factors and no obvious differences between the MSKCC population and our population could be seen. In order to achieve interinstitutional reproducibility, standardization of surgical procedure and of the pathological assessment of the SLN is desirable.

Good Prediction of the Likelihood for Sentinel Lymph Node Metastasis by Using the MSKCC Nomogram in a German Breast Cancer Population

BackgroundThe sentinel lymph node (SLN) procedure could be omitted in cases of accurate prediction of very high or very low probability of SLN metastasis in early breast cancer patients. We evaluated a breast cancer nomogram, an online tool provided by the Memorial Sloan–Kettering Cancer Center (MSKCC), that predicts the likelihood of a positive lymph node.MethodsData from 545 patients with successful SLN biopsy were collected, including 118 patients with a positive sentinel lymph node. Histopathological assessment of the SLN included hematoxylin and eosin staining and/or immunohistochemistry. Predictive accuracy was assessed by calculating the area under the receiver–operator characteristic (ROC) curve.ResultsIn our collective tumor size, histology, lymphovascular infiltration, multifocality, Her-2-neu positivity, and nuclear grade correlated with the probability of SLN metastasis. The ROC of the validated nomogram in our breast cancer population revealed a value of 0.78 compared with 0.75 in the original publication.ConclusionThe MSKCC nomogram is a useful tool in our population of breast cancer patients. However, variations in the pathological assessment of the SLN between breast cancer centers worldwide might be an impediment to widespread application of the nomogram.

Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies

The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors.

Comparison of a reusable with a disposable vessel-sealing device in a sheep model: efficacy and costs

OBJECTIVE To compare the efficacy of the new reusable vessel-sealing device MarSeal (KLS Martin, Tuttlingen, Germany) with the conventional standard disposable LigaSure device (Covidien-Valleylab, Boulder, CO) in an in vivo animal model. DESIGN Prospective animal study. SETTING Center of Experimental Surgery at a university hospital. ANIMALS Thirteen sheep. INTERVENTION(S) The carotid and femoral arteries were dissected bilaterally and sealed randomly with MarSeal unilaterally and consecutively with LigaSure contralaterally in vivo. Afterward the burst pressure was determined for each artery. MAIN OUTCOME MEASURE(S) Sealing time, failure rate, and burst pressure. RESULT(S) The mean diameter of all arteries sealed did not differ significantly between the two groups (MarSeal 5.40 mm vs. LigaSure 5.35 mm). The mean sealing time was significantly shorter with use of the reusable device (MarSeal 5.2 seconds vs. LigaSure 9.1 seconds). We did not find a significant difference in sealing failure rates between the groups (MarSeal 7.0% vs. LigaSure 9.1%). In addition, analysis of mean burst pressure did not reveal a significant difference between the different devices (MarSeal 429 mm Hg vs. LigaSure 484 mm Hg). There was no significant difference with respect to lateral thermal damage (MarSeal 0.91 cm vs. LigaSure 0.93 cm). CONCLUSION(S) In our in vivo animal study, the new reusable MarSeal device appears to be equivalently effective for vessel sealing when compared with the conventional disposable LigaSure device.

Estimates of global research productivity in gynecologic oncology.

Background: Societies worldwide invest considerably in research on oncological diseases of women. However, current literature lacks estimating this research production. We therefore evaluated quality and quantity of publications in gynecologic oncology. Methods: Revisit of 6119 peer-reviewed articles published in Gynecologic Oncology and the International Journal of Gynecological Cancer from January 1996 to December 2006. Descriptive data on disease origin, main topic, and country of origin were collected and analyzed separately. Research productivity was adjusted to the national population and nominal gross domestic product per capita. Results: Research production and international cooperative teamwork in the 2 main journals of gynecologic oncology increased within the 10 last years; 65.3% of all published articles dealt either with epithelial ovarian cancer, cervical cancer, or endometrial cancer. Endometrial cancer had the worst ratio number of publications to estimated national incidence (United States, 2007). The United States (41.15%) and Europe (29.72%) make up a striking 70.87% of the worlds research production in the field of gynecologic oncology. However, the highest rate of increase shows in Turkey (22.5), the Peoples Republic of China (6.87), and South Korea (5.83). Adjusted to the national GDP per capita and population for the year 2006, research productivity seems best in Israel, Austria, and Turkey. Conclusion: Quantitatively, most publications come from the presumed countries. Within the limits of the methodology used in this study, adjustment to population and GDP per capita provides information on research output. The scientific output on endometrial cancer is comparably low.

[Psychological consequences of perinatal loss in subsequent pregnancies--a comparative study].

PURPOSE Pregnancies after perinatal loss occur often. However, little is known about the need of secondary psychological prevention in these instances. Therefore we investigated psychological disorder and distress during the subsequent pregnancy after perinatal loss. METHODS We compared psychological symptoms in pregnant women with and without previous perinatal loss. RESULTS Pregnant women in the PL-group did not suffer more from depression, anxiety and other psychological distress than women without perinatal loss. Nearly a third of the women in the PL-group were classified as unresolved with regard to their mental representation of attachment indicating that their mourning process was still not completed. CONCLUSION Women who have suffered from perinatal loss do not score higher on depression, anxiety or general psychopathology during subsequent pregnancies than women without loss experience. Only a minority of women, who have suffered from loss show ongoing signs of unresolved mourning. However, in order to detect criteria for the identification of those who might be at risk during subsequent pregnancies studies with larger samples size are necessary.

A low-frequency haplotype spanning SLX4/FANCP constitutes a new risk locus for early-onset breast cancer (<60 years) and is associated with reduced DNA repair capacity

Only a fraction of breast cancer (BC) cases can be yet explained by mutations in genes or genomic variants discovered in linkage, genome‐wide association and sequencing studies. The known genes entailing medium or high risk for BC are strongly enriched for a function in DNA double strand repair. Thus, aiming at identifying low frequency variants conferring an intermediate risk, we here investigated 17 variants (MAF: 0.01–0.1) in 10 candidate genes involved in DNA repair or cell cycle control. In an exploration cohort of 437 cases and 1189 controls, we show the variant rs3810813 in the SLX4/FANCP gene to be significantly associated with both BC (≤60 years; OR = 2.6(1.6–3.9), p = 1.6E‐05) and decreased DNA repair capacity (≤60 years; beta = 37.8(17.9–57.8), p = 5.3E‐4). BC association was confirmed in a verification cohort (N = 2441). Both associations were absent from cases diagnosed >60 years and stronger the earlier the diagnosis. By imputation we show that rs3810813 tags a haplotype with 5 additional variants with the same allele frequency (R2 > 0.9), and a pattern of association very similar for both phenotypes (cases <60 years, p < 0.001, the Bonferroni threshold derived from unlinked variants in the region). In young cases (≤60 years) carrying the risk haplotype, micronucleus test results are predictive for BC (AUC > 0.9). Our findings propose a risk variant with high penetrance on the haplotype spanning SLX4/FANCP to be functionally associated to BC predisposition via decreased repair capacity and suggest this variant is carried by a fraction of these haplotypes that is enriched in early onset BC cases.

Abstract PD07-06: Basal-Like Molecular Subtype Predicts Response to Neoadjuvant Chemotherapy with Epirubicine, Cyclophosphamide, and Docetaxel in Patients with Primary Breast Cancer

Background: Gene expression profiling provides an opportunity to predict response to specific regimens of neo-adjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: In a prospective cohort study of 32 women with primary invasive breast cancer with a measurable lesion, we obtained a tumor specimen by high speed core biopsy before and after 4 cycles of NAC with epirubicine 90mg/m2 and cyclophosphamide 600mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100mg/m2. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Agilent9s 44K single color microarray interrogating 44000 unique human genes. Tumor lesions were ultrasonographically measured to assess response using Sinn criteria. Data analysis was performed by GeneSpring v11 and IBM SPSS v18. Results: Using three single sample predictors, 10 tumors were classified as basal-like and 22 tumors were classified as non basal-like. We found that gene expression-based molecular subtype (basal-like vs. non basal-like) (p=0.003), but not tumor grade (p=0.07), estrogen receptor (p=0.1), progesterone receptor (p=0.6), and HER2 status (p=0.4) predicted response to NAC. Specifically, 7/10 basal-like tumors responded to NAC, whereas 19/22 non basal-like tumors did not respond. Comparing gene expression signatures before and after 4 cycles of NAC, we found that all patients with an initial non basal-like tumor retained this tumor type, whereas 5/7 basal-like tumors, including all responders, lost this molecular subtype. Using regression models based on centroid predicition gene sets, complete prediction of response to NAC based on the initial tumor biopsy as well as on the change of gene expression between two tumor biopsies was achieved with a 21 gene list (p=0.000008) and a 23 gene list (p=0.000007), respectively. Of note, both the expression and upregulation of a single gene, ie HER4, predicted response to NAC in 26/32 (81%; p=0.002) and in 23/25 (92%; P Conclusions: Basal-like molecular subtype and therapy-induced HER4 gene upregulation predict response to NAC with epirubicine, cyclophosphamide, and docetaxel. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-06.