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4. Prognostic Impact of Acute and Chronic Inflammatory Interleukin Signatures in the Tumor Microenvironment of Early Breast Cancer.

Author

Heimes, Anne-Sophie, Shehaj, Ina, Almstedt, Katrin, Krajnak, Slavomir, Schwab, Roxana, Stewen, Kathrin, Lebrecht, Antje, Brenner, Walburgis, Hasenburg, Annette, and Schmidt, Marcus

Subjects
BIOMARKERS, BRCA genes, IMMUNE checkpoint proteins, GENE expression, BREAST cancer prognosis, PROPORTIONAL hazards models
Abstract

Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan–Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman–Rho correlation coefficient. Kaplan–Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290–0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune–inflammatory axis. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Efficacy of pembrolizumab in advanced cancer of the vulva: a systematic review and single-arm meta-analysis

Author

Schwab, Roxana, primary, Schiestl, Lina Judit, additional, Cascant Ortolano, Lorena, additional, Klecker, Philip Herbert, additional, Schmidt, Mona Wanda, additional, Almstedt, Katrin, additional, Heimes, Anne-Sophie, additional, Brenner, Walburgis, additional, Stewen, Kathrin, additional, Schmidt, Marcus, additional, and Hasenburg, Annette, additional

Published
2024
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9. BRCA1 , BRCA2 and PALB2 mRNA Expression as Prognostic Markers in Patients with Early Breast Cancer.

Author

Shehaj, Ina, Krajnak, Slavomir, Almstedt, Katrin, Degirmenci, Yaman, Herzog, Sophia, Lebrecht, Antje, Linz, Valerie Catherine, Schwab, Roxana, Stewen, Kathrin, Brenner, Walburgis, Hasenburg, Annette, Schmidt, Marcus, and Heimes, Anne-Sophie

Subjects
GENE expression, BRCA genes, BREAST cancer, PROGNOSIS, METASTATIC breast cancer, BIOMARKERS
Abstract

Breast cancer (BC) poses a challenge in establishing new treatment strategies and identifying new prognostic and predictive markers due to the extensive genetic heterogeneity of BC. Very few studies have investigated the impact of mRNA expression of these genes on the survival of BC patients. Methods: We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis. Results: The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050). Conclusions: According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Prognostic Impact of CD38- and IgκC-Positive Tumor-Infiltrating Plasma Cells in Triple-Negative Breast Cancer

Author

Heimes, Anne-Sophie, primary, Riedel, Natali, additional, Almstedt, Katrin, additional, Krajnak, Slavomir, additional, Schwab, Roxana, additional, Stewen, Kathrin, additional, Lebrecht, Antje, additional, Battista, Marco Johannes, additional, Brenner, Walburgis, additional, Hasenburg, Annette, additional, and Schmidt, Marcus, additional

Published
2023
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11. Supplementary Data from Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

Author

Edlund, Karolina, primary, Madjar, Katrin, primary, Lebrecht, Antje, primary, Aktas, Bahriye, primary, Pilch, Henryk, primary, Hoffmann, Gerald, primary, Hofmann, Manfred, primary, Kolberg, Hans-Christian, primary, Boehm, Daniel, primary, Battista, Marco, primary, Seehase, Martina, primary, Stewen, Kathrin, primary, Gebhard, Susanne, primary, Cadenas, Cristina, primary, Marchan, Rosemarie, primary, Brenner, Walburgis, primary, Hasenburg, Annette, primary, Koelbl, Heinz, primary, Solbach, Christine, primary, Gehrmann, Mathias, primary, Tanner, Berno, primary, Weber, Karsten E., primary, Loibl, Sibylle, primary, Sachinidis, Agapios, primary, Rahnenführer, Jörg, primary, Schmidt, Marcus, primary, and Hengstler, Jan G., primary

Published
2023
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12. Current Approaches to the Management of Sentinel Node Procedures in Early Vulvar Cancer in Germany: A Web-Based Nationwide Analysis of Practices

Author

Schwab, Roxana, primary, Stewen, Kathrin, additional, Bührer, Theresa-Louise, additional, Schmidt, Mona W., additional, van der Ven, Josche, additional, Anic, Katharina, additional, Linz, Valerie C., additional, Hamoud, Bashar Haj, additional, Brenner, Walburgis, additional, Peters, Katharina, additional, Heimes, Anne-Sophie, additional, Almstedt, Katrin, additional, Krajnak, Slavomir, additional, Weikel, Wolfgang, additional, Battista, Marco J., additional, Dannecker, Christian, additional, and Hasenburg, Annette, additional

Published
2023
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13. Discordance of HER2-Low between Primary Tumors and Matched Distant Metastases in Breast Cancer

Author

Almstedt, Katrin, primary, Krauthauser, Lisa, additional, Kappenberg, Franziska, additional, Wagner, Daniel-Christoph, additional, Heimes, Anne-Sophie, additional, Battista, Marco J., additional, Anic, Katharina, additional, Krajnak, Slavomir, additional, Lebrecht, Antje, additional, Schwab, Roxana, additional, Brenner, Walburgis, additional, Weikel, Wolfgang, additional, Rahnenführer, Jörg, additional, Hengstler, Jan G., additional, Roth, Wilfried, additional, Hasenburg, Annette, additional, Stewen, Kathrin, additional, and Schmidt, Marcus, additional

Published
2023
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14. Prognostic Impact of LAG-3 mRNA Expression in Early Breast Cancer

Author

Heimes, Anne-Sophie, primary, Almstedt, Katrin, additional, Krajnak, Slavomir, additional, Runkel, Anne, additional, Droste, Annika, additional, Schwab, Roxana, additional, Stewen, Kathrin, additional, Lebrecht, Antje, additional, Battista, Marco J., additional, Brenner, Walburgis, additional, Hasenburg, Annette, additional, Gehrmann, Mathias, additional, Hengstler, Jan G., additional, and Schmidt, Marcus, additional

Published
2022
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16. Prognostic Impact of LAG-3 Expression in Early Breast Cancer

Author

Heimes, Anne-Sophie, primary, Almstedt, Katrin, additional, Krajnak, Slavomir, additional, Runkel, Anne, additional, Droste, Annika, additional, Schwab, Roxana, additional, Stewen, Kathrin, additional, Lebrecht, Antje, additional, Battista, Marco J., additional, Brenner, Walburgis, additional, Hasenburg, Annette, additional, Gehrmann, Mathias, additional, Hengstler, Jan G., additional, and Schmidt, Marcus, additional

Published
2022
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20. Resilience as a Source of Easement to Health-Related Worries in Women at Increased Risk for Breast or Ovarian Cancer During the COVID-19 Pandemic

Author

Schwab,Roxana, Droste,Annika, Stewen,Kathrin, Elger,Tania, Theis,Susanne, Heimes,Anne-Sophie, Peters,Katharina, Schmidt,Marcus, Brenner,Walburgis, Hasenburg,Annette, Schwab,Roxana, Droste,Annika, Stewen,Kathrin, Elger,Tania, Theis,Susanne, Heimes,Anne-Sophie, Peters,Katharina, Schmidt,Marcus, Brenner,Walburgis, and Hasenburg,Annette

Abstract

Roxana Schwab, Annika Droste, Kathrin Stewen, Tania Elger, Susanne Theis, Anne-Sophie Heimes, Katharina Peters, Marcus Schmidt, Walburgis Brenner, Annette Hasenburg Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55131, GermanyCorrespondence: Roxana Schwab, Department of Obstetrics and Gynecology, University Medical Center of the Johannes, Gutenberg University Mainz, Mainz, 55131, Germany, Tel +49-6131-17-0, Fax +49-6131-17-5692, Email roxana.schwab@unimedizin-mainz.dePurpose: The COVID-19 pandemic has affected individuals’ and society’s physical and psychological well-being. The study was conducted in order to assess the predictors for health-related worries during the COVID-19 pandemic in vulnerable populations.Patients and Methods: A cross-sectional web-based survey of women who had a higher risk of developing breast cancer (BC) or ovarian cancer (OC) was conducted, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire was designed for this study to assess health-related worries. The PHQ-4 questionnaire was used to evaluate mental health, and the Brief Resilience Scale (BRS) questionnaire was employed to investigate resilience.Results: History of BC or OC was recognized as an independent significant risk factor for worries regarding being more susceptible to a more severe course of COVID-19 disease (OR 3.593; 95% CI 1.030– 12.536; p = 0.045). High scores in the BRS questionnaire were negatively correlated with health-related worries, such as an increased risk for occurrence of BC or OC (OR 0.332; 95% CI 0.118– 0.933; p = 0.37) or worsening of oncological outcome as a result of an infection with the SARS-CoV-2 virus (OR 0.330; 95% I 0.114– 0.956; p = 0.041).Conclusion: The obtained findings determined resilience as an independent and potent protective parameter in terms of health-related concerns in women at high risk

Published
2022

23. Long-Term Prognostic Significance of HER2-Low and HER2-Zero in Node-Negative Breast Cancer

Author

Almstedt, Katrin, primary, Heimes, Anne-Sophie, additional, Kappenberg, Franziska, additional, Battista, Marco J., additional, Lehr, Hans-Anton, additional, Krajnak, Slavomir, additional, Lebrecht, Antje, additional, Gehrmann, Mathias, additional, Stewen, Kathrin, additional, Brenner, Walburgis, additional, Weikel, Wolfgang, additional, Rahnenführer, Jörg, additional, Hengstler, Jan G., additional, Hasenburg, Annette, additional, and Schmidt, Marcus, additional

Published
2022
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24. Pain experience and social support of endometriosis patients during the COVID-19 pandemic in Germany – results of a web-based cross-sectional survey

Author

Schwab, Roxana, primary, Anić, Katharina, additional, Stewen, Kathrin, additional, Schmidt, Mona W., additional, Kalb, Stefanie R., additional, Kottmann, Tanja, additional, Brenner, Walburgis, additional, Domidian, Jana-Sophie, additional, Krajnak, Slavomir, additional, Battista, Marco J., additional, and Hasenburg, Annette, additional

Published
2021
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25. Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

Author

Edlund, Karolina, Madjar, Katrin, Lebrecht, Antje, Aktas, Bahriye, Pilch, Henryk, Hoffmann, Gerald, Hofmann, Manfred, Kolberg, Hans-Christian, Boehm, Daniel, Battista, Marco, Seehase, Martina, Stewen, Kathrin, Gebhard, Susanne, Cadenas, Cristina, Marchan, Rosemarie, Brenner, Walburgis, Hasenburg, Annette, Koelbl, Heinz, Solbach, Christine, Gehrmann, Mathias, Tanner, Berno, Weber, Karsten E., Loibl, Sibylle, Sachinidis, Agapios, Rahnenfuehrer, Joerg, Schmidt, Marcus, Hengstler, Jan G., Edlund, Karolina, Madjar, Katrin, Lebrecht, Antje, Aktas, Bahriye, Pilch, Henryk, Hoffmann, Gerald, Hofmann, Manfred, Kolberg, Hans-Christian, Boehm, Daniel, Battista, Marco, Seehase, Martina, Stewen, Kathrin, Gebhard, Susanne, Cadenas, Cristina, Marchan, Rosemarie, Brenner, Walburgis, Hasenburg, Annette, Koelbl, Heinz, Solbach, Christine, Gehrmann, Mathias, Tanner, Berno, Weber, Karsten E., Loibl, Sibylle, Sachinidis, Agapios, Rahnenfuehrer, Joerg, Schmidt, Marcus, and Hengstler, Jan G.

Abstract

Purpose: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. Patients and Methods: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). Results: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. Conclusions: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.

Published
2021

26. Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

Author

Edlund, Karolina, primary, Madjar, Katrin, additional, Lebrecht, Antje, additional, Aktas, Bahriye, additional, Pilch, Henryk, additional, Hoffmann, Gerald, additional, Hofmann, Manfred, additional, Kolberg, Hans-Christian, additional, Boehm, Daniel, additional, Battista, Marco, additional, Seehase, Martina, additional, Stewen, Kathrin, additional, Gebhard, Susanne, additional, Cadenas, Cristina, additional, Marchan, Rosemarie, additional, Brenner, Walburgis, additional, Hasenburg, Annette, additional, Koelbl, Heinz, additional, Solbach, Christine, additional, Gehrmann, Mathias, additional, Tanner, Berno, additional, Weber, Karsten E., additional, Loibl, Sibylle, additional, Sachinidis, Agapios, additional, Rahnenführer, Jörg, additional, Schmidt, Marcus, additional, and Hengstler, Jan G., additional

Published
2021
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