Publications by authors named "Ella Asseryanis"

8 Publications

  • Page 1 of 1

Tissue Sodium Concentration Quantification at 7.0-T MRI as an Early Marker for Chemotherapy Response in Breast Cancer: A Feasibility Study.

Radiology 2021 04 16;299(1):63-72. Epub 2021 Feb 16.

From the Institute for Clinical Molecular MRI in Musculoskeletal System, Karl Landsteiner Society, Vienna, Austria (O.Z., S.T.); Breast Health Center, Department of Obstetrics and Gynecology (A.F., E.A., C.F.S.), and High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy (L.M., M.W., S.T.), Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (S.L., A.M.N.); and Christian Doppler Laboratory for Clinical Molecular MRI, Christian Doppler Forschungsgesellschaft, Vienna, Austria (S.T.).

Background Tissue sodium concentration (TSC) is elevated in breast cancer and can determine chemotherapy response. Purpose To test the feasibility of using a sodium 23 (Na) MRI protocol at 7.0 T for TSC quantification to predict early treatment outcomes of neoadjuvant chemotherapy in breast cancer and to determine whether those quantitative values provide additional information about efficacy. Materials and Methods Women with primary breast cancer were included in this prospective study. From July 2017 to June 2018, participants underwent 7.0-T Na MRI. Multichannel data sets were acquired with a density-adapted, three-dimensional radial projection reconstruction pulse sequence. Two-dimensional tumor size and TSC were evaluated before and after the first and second chemotherapy cycle, and statistical tests were performed based on the presence or absence of a pathologic complete response (pCR). Results Fifteen women with breast cancer and six healthy women were enrolled. The mean baseline tumor size in women with a pCR was 7.0 cm ± 5.0 (standard deviation), and the mean baseline tumor size in women without a pCR was 19.0 cm ± 12.0. After the first chemotherapy cycle, women with a pCR showed a reduced tumor size of 32.9% (2.3 cm/7.0 cm), compared with 15.3% (2.9 cm/19.0 cm) in those without a pCR. The areas under the receiver operating characteristic curve for tumor size reduction after the first and second chemotherapy cycle were 0.73 (95% CI: 0.09, 0.50; = .12) and 0.93 (95% CI: 0.04, 0.60; < .001), respectively. Women with a pCR had a mean baseline TSC of 69.4 mmol/L ± 6.1, with a reduction of 12.0% (8.3 mmol/L), whereas those without a pCR had a mean baseline TSC of 71.7 mmol/L ± 5.7, with a reduction of 4.7% (3.4 mmol/L) after the first cycle. The areas under the receiver operating characteristic curve for TSC after the first and second cycles were 0.96 (95% CI: 0.86, 1.00; < .001) and 1.000 (95% CI: 1.00, < .001), respectively. Conclusion Using 7.0-T MRI for tissue sodium concentration quantification to predict early treatment outcomes of neoadjuvant chemotherapy in breast cancer is feasible, with reduced tissue sodium concentration indicative of cancer response. © RSNA, 2021
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April 2021

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Genet Epidemiol 2020 07 1;44(5):442-468. Epub 2020 Mar 1.

Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
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July 2020

The :p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

NPJ Breast Cancer 2019 1;5:38. Epub 2019 Nov 1.

25University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, TX USA.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes , , , , and are associated with breast cancer risk. , which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants :p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of or . These three variants were also studied functionally by measuring survival and chromosome fragility in patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that :p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44,  = 0.034 and OR = 3.79;  = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for :p.Arg658* and found that also :p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96;  = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with :p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat -associated tumors.
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November 2019

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Nat Commun 2019 04 15;10(1):1741. Epub 2019 Apr 15.

Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), 28040, Madrid, Spain.

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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April 2019

7T CEST MRI: A potential imaging tool for the assessment of tumor grade and cell proliferation in breast cancer.

Magn Reson Imaging 2019 06 14;59:77-87. Epub 2019 Mar 14.

High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Clinical Molecular MRI, Christian Doppler Forschungsgesellschaft, Vienna, Austria.

Objectives: To investigate the feasibility of chemical exchange saturation transfer (CEST) MRI in patients with breast carcinomas and possible correlations between magnetization transfer asymmetry (MTR) values and histological features, such as tumor grade and the Ki-67 proliferation index.

Materials And Methods: Nine healthy subjects and 18 female patients were enrolled for this study. The imaging protocol for the patients consisted of diffusion-weighted imaging (DWI), CEST imaging, and T1-weighted, contrast-enhanced (CE)-MRI. CEST was performed using a 3D gradient echo (GRE) sequence, employing eight pre-saturation pulses of a duration of 50 ms and a duty cycle (DC) of 80%, with a mean amplitude of the saturation pulse train of 1 μT. The Z-spectrum was plotted and MTR values calculated for the frequency of the maximum of MTR curve, were correlated with the Ki-67 proliferation index and apparent diffusion coefficient (ADC). Patient data were statistically assessed using the Games-Howell post-hoc and Pearson's correlation test.

Results: Different tumor types had asymmetry peaks at different positions of Z-spectrum. MTR (mean ± SD) (%) calculated for G1 (3.0 ± 0.3; range: 2.70-3.50) was not significantly lower than for G2 (4.50 ± 1.30; range: 3.20-6.50; p = 0.066). In contrast, the increase in MTR between G1 and G3 (6.40 ± 1.70; range: 4.80-9.80) lesions was significant (p = 0.007). No significant difference was observed between G2 and G3 with regard to MTR (p = 0.089). There was a strong positive correlation between the MTR, and Ki-67 proliferation index (r = 0.890; p = 0.001), while there was a moderate negative correlation between MTR and ADC values (r = -0.506; p = 0.027).

Conclusions: Calculated MTR demonstrates a strong positive correlation with tumor proliferation and has the potential to become a valuable biomarker for breast tumor characterization.
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June 2019

Improving comprehension of genetic counseling for hereditary breast and ovarian cancer clients with a visual tool.

PLoS One 2018 12;13(7):e0200559. Epub 2018 Jul 12.

Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Objective: Genetic counseling and testing can be offered to individuals who are at high risk of carrying a breast cancer (BRCA) gene mutation. However, the content of genetic counseling could be difficult to understand due to complex medical information. The aim of this study was to investigate if comprehension can be improved with a new genetic counseling tool (NGCT hereafter; a tool that combines complex medical information with pictures, diagrams and tables) as compared to conventional oral-only genetic counseling (CGC).

Methods: 207 clients attended genetic counseling for hereditary breast and ovarian cancer at the Medical University of Vienna between February 2015 and February 2016. Seventy clients participated in this study and were allocated into two groups: the first 36 participants received conventional (oral only) genetic counseling (CGC) and the following 34 participants received genetic counseling using a new genetic counseling tool (NGCT), which combines complex information with pictures, diagrams and tables. After genetic counseling, all consenting participants were invited to complete a questionnaire with seven questions evaluating their comprehension of the medical information provided.

Results: Socio-demographic backgrounds were comparable in both groups. Correct responses were significantly higher in the NGCT group compared to the CGC group (p = 0.012). NGCT also statistically improves correct response of Q1 (p = 0.03) and Q7 (p = 0.004).

Conclusion: The NGCT leads to an overall better understanding of the content of a genetic counseling session than CGC alone.
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January 2019

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Hum Mutat 2018 05 12;39(5):593-620. Epub 2018 Mar 12.

Lunenfeld-Tanenbaum Research Institute, Toronto, Canada.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
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May 2018

Surgical breast lesions in adolescent females.

Pediatr Surg Int 2009 Jan 5;25(1):73-5. Epub 2008 Nov 5.

Division of Senology, Department of OB/GYN, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Purpose: Breast diseases in teenage girls are fortunately uncommon, with most presenting masses being benign. The aim of this study was to evaluate the histopathological results of breast lesions excised from adolescent females less than 19 years of age.

Methods: The authors reviewed the medical and pathology records at the University Hospital of Vienna, Department of Obstetrics and Gynaecology, between 1993 and 2006, retrospectively. All data included the patient age, age of menarche, pregnancy, hormonal contraception, family history of breast cancer, size of the breast lesion and its histopathology following surgery.

Results: Thirty-seven female patients with an average age of 16 years (ranging 12-18 years) were operated on for breast tumor and/or discharge. All tumors were palpable. Six patients had bilateral breast masses; thus, 43 breast lesions were evaluated following surgical excision. Surprisingly, breast cancer was found in two cases. Both patients were diagnosed with a noninvasive ductal carcinoma in situ (DCIS) within a fibroadenoma at the age of 16. These are the first reported cases of DCIS found in this young age group. As breast neoplasm was found in two cases, a malignancy rate of 4.7% was observed. The most common histologies were fibroadenoma (n=27) and fibrocystic disease (n=4).

Conclusion: The incidence of primary breast cancer in adolescent women is low. However, our experience shows the need for compulsory excision of all breast masses and highlighting the importance of histopathological evaluation of all breast tumors including adolescents.
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January 2009