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2. High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial

Author

Vliek, Sonja, Hilbers, Florentine S., van Werkhoven, Erik, Mandjes, Ingrid, Kessels, Rob, Kleiterp, Sieta, Lips, Esther H., Mulder, Lennart, Kayembe, Mutamba T., Loo, Claudette E., Russell, Nicola S., Vrancken Peeters, Marie-Jeanne T. F. D., Holtkamp, Marjo J., Schot, Margaret, Baars, Joke W., Honkoop, Aafke H., Vulink, Annelie J. E., Imholz, Alex L. T., Vrijaldenhoven, Suzan, van den Berkmortel, Franchette W. P. J., Meerum Terwogt, Jetske M., Schrama, Jolanda G., Kuijer, Philomeen, Kroep, Judith R., van der Padt-Pruijsten, Annemieke, Wesseling, Jelle, Sonke, Gabe S., Gilhuijs, Kenneth G. A., Jager, Agnes, Nederlof, Petra, and Linn, Sabine C.

Published
2023
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3. PROACTING: predicting pathological complete response to neoadjuvant chemotherapy in breast cancer from routine diagnostic histopathology biopsies with deep learning

Author

Aswolinskiy, Witali, Munari, Enrico, Horlings, Hugo M., Mulder, Lennart, Bogina, Giuseppe, Sanders, Joyce, Liu, Yat-Hee, van den Belt-Dusebout, Alexandra W., Tessier, Leslie, Balkenhol, Maschenka, Stegeman, Michelle, Hoven, Jeffrey, Wesseling, Jelle, van der Laak, Jeroen, Lips, Esther H., and Ciompi, Francesco

Published
2023
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6. DCIS knowledge of women choosing between active surveillance and surgery for low-risk DCIS

Author

Thompson, Alastair, Nik-Zainal, Serena, Sawyer, Elinor J., Davies, Helen, Futreal, Andrew, Navin, Nicholas, Hwang, E. Shelley, Jonkers, Jos, van Rheenen, Jacco, Behbod, Fariba, Lips, Esther H., Schmidt, Marjanka, Wessels, Lodewyk F.A., Rea, Daniel, Bhattacharjee, Proteeti, Stobart, Hilary, Collyar, Deborah, Pinto, Donna, van Oirsouw, Marja, Alaeikhanehshir, S., Elshof, L., Engelhardt, E.G., Schmitz, R.S.J.M., Gerritsma, M.A., Sondermeijer, C.M.T., Verschuur, E., Houtzager, J.H.E., Griffioen, R., Bijker, N., Mann, R.M., Retèl, V., van Duijnhoven, F.H., Wesseling, J., and Bleiker, E.M.A.

Published
2024
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8. Characterization of Oligometastatic Disease in a Real-World Nationwide Cohort of 3447 Patients With de Novo Metastatic Breast Cancer.

Author

Steenbruggen, Tessa G, Schaapveld, Michael, Horlings, Hugo M, Sanders, Joyce, Hogewoning, Sander J, Lips, Esther H, Vrancken Peeters, Marie-Jeanne T, Kok, Niels F, Wiersma, Terry, Esserman, Laura, van 't Veer, Laura J, Linn, Sabine C, Siesling, Sabine, and Sonke, Gabe S

Abstract

BackgroundObservational studies in metastatic breast cancer (MBC) show that long-term overall survival (OS) is associated with limited tumor burden, or oligo-MBC (OMBC). However, a uniform definition of OMBC is lacking. In this real-world nationwide cohort, we aimed to define the optimal OMBC threshold and factors associated with survival in patients with OMBC.Methods3535 patients aged younger than 80 years at diagnosis of de novo MBC in the Netherlands between January 2000 and December 2007 were included. Detailed clinical, therapy, and outcome data were collected from medical records of a sample of the patients. Using inverse-sampling-probability weighting, the analysis cohort (n = 3447) was constructed. We assessed OS according to number of metastases at diagnosis to determine the optimal OMBC threshold. Next, we applied Cox regression models with inverse-sampling-probability weighting to study associations with OS and progression-free survival in OMBC. All statistical tests were 2-sided.ResultsCompared with more than 5 distant metastases, adjusted hazard ratios for OS (with 95% confidence interval [CI] based on robust standard errors) for 1, 2-3, and 4-5 metastases were 0.70 (95% CI = 0.52 to 0.96), 0.63 (95% CI = 0.45 to 0.89), and 0.91 (95% CI = 0.61 to 1.37), respectively. Ten-year OS estimates for patients with no more than 3 vs more than 3 metastases were 14.9% and 3.4% (P

Published
2021

12. Archival single-cell genomics reveals persistent subclones during DCIS progression

Author

Wang, Kaile, Kumar, Tapsi, Wang, Junke, Minussi, Darlan Conterno, Sei, Emi, Li, Jianzhuo, Tran, Tuan M., Thennavan, Aatish, Hu, Min, Casasent, Anna K., Xiao, Zhenna, Bai, Shanshan, Yang, Lei, King, Lorraine M., Shah, Vandna, Kristel, Petra, van der Borden, Carolien L., Marks, Jeffrey R., Zhao, Yuehui, Zurita, Amado J., Aparicio, Ana, Chapin, Brian, Ye, Jie, Zhang, Jianjun, Gibbons, Don L., Sawyer, Ellinor, Thompson, Alastair M., Futreal, Andrew, Hwang, E. Shelley, Wesseling, Jelle, Lips, Esther H., and Navin, Nicholas E.

Published
2023
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14. A living biobank of patient-derived ductal carcinoma in situ mouse-intraductal xenografts identifies risk factors for invasive progression

Author

Hutten, Stefan J., de Bruijn, Roebi, Lutz, Catrin, Badoux, Madelon, Eijkman, Timo, Chao, Xue, Ciwinska, Marta, Sheinman, Michael, Messal, Hendrik, Herencia-Ropero, Andrea, Kristel, Petra, Mulder, Lennart, van der Waal, Rens, Sanders, Joyce, Almekinders, Mathilde M., Llop-Guevara, Alba, Davies, Helen R., van Haren, Matthijs J., Martin, Nathaniel I., Behbod, Fariba, Nik-Zainal, Serena, Serra, Violeta, van Rheenen, Jacco, Lips, Esther H., Wessels, Lodewyk F.A., Wesseling, Jelle, Scheele, Colinda L.G.J., and Jonkers, Jos

Published
2023
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15. Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests

Author

Meijer, Titia G., Nguyen, Luan, Van Hoeck, Arne, Sieuwerts, Anieta M., Verkaik, Nicole S., Ladan, Marjolijn M., Ruigrok-Ritstier, Kirsten, van Deurzen, Carolien H. M., van de Werken, Harmen J. G., Lips, Esther H., Linn, Sabine C., Memari, Yasin, Davies, Helen, Nik-Zainal, Serena, Kanaar, Roland, Martens, John W. M., Cuppen, Edwin, Jager, Agnes, and van Gent, Dik C.

Published
2022
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16. Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

Author

Lips, Esther H., Kumar, Tapsi, Megalios, Anargyros, Visser, Lindy L., Sheinman, Michael, Fortunato, Angelo, Shah, Vandna, Hoogstraat, Marlous, Sei, Emi, Mallo, Diego, Roman-Escorza, Maria, Ahmed, Ahmed A., Xu, Mingchu, van den Belt-Dusebout, Alexandra W., Brugman, Wim, Casasent, Anna K., Clements, Karen, Davies, Helen R., Fu, Liping, Grigoriadis, Anita, Hardman, Timothy M., King, Lorraine M., Krete, Marielle, Kristel, Petra, de Maaker, Michiel, Maley, Carlo C., Marks, Jeffrey R., Menegaz, Brian A., Mulder, Lennart, Nieboer, Frank, Nowinski, Salpie, Pinder, Sarah, Quist, Jelmar, Salinas-Souza, Carolina, Schaapveld, Michael, Schmidt, Marjanka K., Shaaban, Abeer M., Shami, Rana, Sridharan, Mathini, Zhang, John, Stobart, Hilary, Collyar, Deborah, Nik-Zainal, Serena, Wessels, Lodewyk F. A., Hwang, E. Shelley, Navin, Nicholas E., Futreal, P. Andrew, Thompson, Alastair M., Wesseling, Jelle, and Sawyer, Elinor J.

Published
2022
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17. Locoregional Breast Cancer Recurrence in the European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 MINDACT Trial: Analysis of Risk Factors Including the 70-Gene Signature

Author

Alaeikhanehshir, Sena, primary, Ajayi, Taiwo, additional, Duijnhoven, Frederieke H., additional, Poncet, Coralie, additional, Olaniran, Ridwan O., additional, Lips, Esther H., additional, van 't Veer, Laura J., additional, Delaloge, Suzette, additional, Rubio, Isabel T., additional, Thompson, Alastair M., additional, Cardoso, Fatima, additional, Piccart, Martine, additional, and Rutgers, Emiel J.T., additional

Published
2024
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19. Ductal carcinoma in situ develops within clonal fields of mutant cells in morphologically normal ducts.

Author

Hutten, Stefan J, Messal, Hendrik A, Lips, Esther H, Sheinman, Michael, Ciwinska, Marta, Braams, Esmee, van der Borden, Carolien, Kristel, Petra, Stoffers, Saskia, Wessels, Lodewyk FA, Wesseling, Jelle, Jonkers, Jos, van Rheenen, Jacco, Schmidt, Marjanka, Bhattacharjee, Proteeti, Thompson, Alastair, Nik‐Zainal, Serena, Davies, Helen, Sawyer, Elinor J, and Futreal, Andrew

Subjects
DUCTAL carcinoma, PRECANCEROUS conditions, CARCINOMA in situ, BREAST cancer, EPITHELIUM, GENOMICS
Abstract

Mutations are abundantly present in tissues of healthy individuals, including the breast epithelium. Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field of mutant cells that is predisposed towards lesion formation. To study the clonal and spatial relationships between morphologically normal breast epithelium adjacent to pre‐cancerous lesions, we developed a three‐dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival, formalin‐fixed breast tissue with the non‐obligate breast cancer precursor ductal carcinoma in situ (DCIS). Using this 3D image‐guided characterization method, we built high‐resolution spatial maps of DNA copy number aberration (CNA) profiles within the DCIS lesion and the surrounding normal mammary ducts. We show that the local heterogeneity within a DCIS lesion is limited. However, by mapping the CNA profiles back onto the 3D reconstructed ductal subtree, we find that in eight out of 16 cases the healthy epithelium adjacent to the DCIS lesions has overlapping structural variations with the CNA profile of the DCIS. Together, our study indicates that pre‐malignant breast transformations frequently develop within mutant clonal fields of morphologically normal‐looking ducts. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study

Author

Schmitz, Renée S J M, primary, van den Belt-Dusebout, Alexandra W, additional, Clements, Karen, additional, Ren, Yi, additional, Cresta, Chiara, additional, Timbres, Jasmine, additional, Liu, Yat-Hee, additional, Byng, Danalyn, additional, Lynch, Thomas, additional, Menegaz, Brian A, additional, Collyar, Deborah, additional, Hyslop, Terry, additional, Thomas, Samantha, additional, Love, Jason K, additional, Schaapveld, Michael, additional, Bhattacharjee, Proteeti, additional, Ryser, Marc D, additional, Sawyer, Elinor, additional, Hwang, E Shelley, additional, Thompson, Alastair, additional, Wesseling, Jelle, additional, Lips, Esther H, additional, and Schmidt, Marjanka K, additional

Published
2023
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28. Microcalcification crystallography as a potential marker of DCIS recurrence

Author

Gosling, Sarah B, Arnold, Emily L, Davies, Samantha K, Cross, Hannah, Bouybayoune, Ihssane, Calabrese, Doriana, Nallala, Jayakrupakar, Pinder, Sarah E, Fu, Liping, Lips, Esther H, King, Lorraine, Marks, Jeffrey, Hall, Allison, Grimm, Lars J, Lynch, Thomas, Pinto, Donna, Stobart, Hilary, Hwang, E Shelley, Wesseling, Jelle, Geraki, Kalotina, Stone, Nicholas, Lyburn, Iain D, Greenwood, Charlene, Rogers, Keith D, Grand Challenge PRECISION Consortium, Gosling, Sarah B [0000-0002-7034-6547], Arnold, Emily L [0000-0001-5469-2071], Davies, Samantha K [0000-0002-1819-1904], Cross, Hannah [0000-0002-5339-4432], Bouybayoune, Ihssane [0000-0002-7185-1991], Calabrese, Doriana [0000-0002-3868-9830], Nallala, Jayakrupakar [0000-0002-9473-5782], and Apollo - University of Cambridge Repository

Subjects
Carcinoma, Intraductal, Noninfiltrating, Crystallography, Carcinoma, Ductal, Breast, Tumor Microenvironment, Humans, Calcinosis, Female, Breast Neoplasms, Neoplasm Recurrence, Local
Abstract

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.

Published
2023

29. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer

Author

Lips, Esther H, Mukhtar, Rita A, Yau, Christina, de Ronde, Jorma J, Livasy, Chad, Carey, Lisa A, Loo, Claudette E, Vrancken-Peeters, Marie-Jeanne TFD, Sonke, Gabe S, Berry, Donald A, van‘t Veer, Laura J, Esserman, Laura J, Wesseling, Jelle, Rodenhuis, Sjoerd, Shelley Hwang, E, and I-SPY TRIAL Investigators

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Adult, Aged, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Clinical Trials as Topic, Female, Gene Expression Regulation, Neoplastic, Humans, Mastectomy, Segmental, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness, Neoplasm Staging, Receptor, ErbB-2, Treatment Outcome, Neoadjuvant chemotherapy, Lobular breast cancer, Gene expression arrays, Predictive factors, I-SPY TRIAL Investigators, Receptor, erbB-2, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.

Published
2012

31. Abstract 125: Archival single cell sequencing reveals persistent subclones over years to decades of DCIS progression

Author

Wang, Kaile, primary, Kumar, Tapsi, additional, wang, Junke, additional, Minussi, Darlan, additional, Sei, Emi, additional, li, Jianzhuo, additional, Tran, Tuan, additional, Thennavan, Aatish, additional, Hu, Min, additional, Casasent, Anna, additional, Xiao, Zhenna, additional, Bai, Shanshan, additional, Zhao, Yuehui, additional, Zurita, Amado, additional, Aparicio, Ana, additional, Chapin, Brian, additional, ye, Jie, additional, Zhang, Jianjun, additional, Gibbons, Don, additional, Futreal, Andrew, additional, King, Lorraine, additional, Marks, Jeffrey, additional, Hwang, E. Shelley, additional, Shah, Vandna, additional, Sawyer, Ellinor, additional, Kristel, Petra, additional, Wesseling, Jelle, additional, Lips, Esther H., additional, and Navin, Nicholas, additional

Published
2023
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32. Supplementary table 2 from BRCA1-Mutated Estrogen Receptor–Positive Breast Cancer Shows BRCAness, Suggesting Sensitivity to Drugs Targeting Homologous Recombination Deficiency

Author

Lips, Esther H., primary, Debipersad, Rashmie D., primary, Scheerman, Caroline E., primary, Mulder, Lennart, primary, Sonke, Gabe S., primary, van der Kolk, Lizet E., primary, Wesseling, Jelle, primary, Hogervorst, Frans B.L., primary, and Nederlof, Petra M., primary

Published
2023
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34. Supplementary Data from Prognostic Value of Residual Disease after Neoadjuvant Therapy in HER2-Positive Breast Cancer Evaluated by Residual Cancer Burden, Neoadjuvant Response Index, and Neo-Bioscore

Author

Steenbruggen, Tessa G., primary, van Seijen, Maartje, primary, Janssen, Liselore M., primary, van Ramshorst, Mette S., primary, van Werkhoven, Erik, primary, Vrancken Peeters, Marie-Jeanne T.D.F., primary, Wesseling, Jelle, primary, Lips, Esther H., primary, and Sonke, Gabe S., primary

Published
2023
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35. Supplementary table 1 from BRCA1-Mutated Estrogen Receptor–Positive Breast Cancer Shows BRCAness, Suggesting Sensitivity to Drugs Targeting Homologous Recombination Deficiency

Author

Lips, Esther H., primary, Debipersad, Rashmie D., primary, Scheerman, Caroline E., primary, Mulder, Lennart, primary, Sonke, Gabe S., primary, van der Kolk, Lizet E., primary, Wesseling, Jelle, primary, Hogervorst, Frans B.L., primary, and Nederlof, Petra M., primary

Published
2023
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36. Figure S1 from Prognostic Value of Residual Disease after Neoadjuvant Therapy in HER2-Positive Breast Cancer Evaluated by Residual Cancer Burden, Neoadjuvant Response Index, and Neo-Bioscore

Author

Steenbruggen, Tessa G., primary, van Seijen, Maartje, primary, Janssen, Liselore M., primary, van Ramshorst, Mette S., primary, van Werkhoven, Erik, primary, Vrancken Peeters, Marie-Jeanne T.D.F., primary, Wesseling, Jelle, primary, Lips, Esther H., primary, and Sonke, Gabe S., primary

Published
2023
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37. Supplementary Materials and Methods from Clinicopathological Risk Factors for an Invasive Breast Cancer Recurrence after Ductal Carcinoma In Situ—A Nested Case–Control Study

Author

Visser, Lindy L., primary, Elshof, Lotte E., primary, Schaapveld, Michael, primary, van de Vijver, Koen, primary, Groen, Emma J., primary, Almekinders, Mathilde M., primary, Bierman, Carolien, primary, van Leeuwen, Flora E., primary, Rutgers, Emiel J., primary, Schmidt, Marjanka K., primary, Lips, Esther H., primary, and Wesseling, Jelle, primary

Published
2023
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39. Supplemental Table S1 from Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer

Author

Wijdeven, Ruud H., primary, Pang, Baoxu, primary, van der Zanden, Sabina Y., primary, Qiao, Xiaohang, primary, Blomen, Vincent, primary, Hoogstraat, Marlous, primary, Lips, Esther H., primary, Janssen, Lennert, primary, Wessels, Lodewyk, primary, Brummelkamp, Thijn R., primary, and Neefjes, Jacques, primary

Published
2023
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40. Supplemental Figures 1 - 4 from Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer

Author

Wijdeven, Ruud H., primary, Pang, Baoxu, primary, van der Zanden, Sabina Y., primary, Qiao, Xiaohang, primary, Blomen, Vincent, primary, Hoogstraat, Marlous, primary, Lips, Esther H., primary, Janssen, Lennert, primary, Wessels, Lodewyk, primary, Brummelkamp, Thijn R., primary, and Neefjes, Jacques, primary

Published
2023
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43. Characterization of the Tumor Microenvironment of De Novo Oligometastatic Breast Cancer in a Nationwide Cohort.

Author

Steenbruggen, Tessa G., Wolf, Denise M., Thijssen, Bram, Sanders, Joyce, Cornelissen, Sten, Salgado, Roberto, Mittempergher, Lorenza, Bhaskaran, Rajith, Broeks, Annegien, Lips, Esther H., Siesling, Sabine, Sonke, Gabe S., Horlings, Hugo M., and van 't Veer, Laura J.

Subjects
TUMOR-infiltrating immune cells, EPIDERMAL growth factor receptors, TUMOR microenvironment, BREAST cancer, METASTATIC breast cancer
Abstract

Extracellular-matrix features distinguish between long-term versus shorter-term survivors with OligoMBC. PURPOSE: Oligometastatic breast cancer (OMBC) has a more favorable outcome than widespread metastatic breast cancer. Some patients with OMBC achieve long-term remission if treated with multimodality therapy, including systemic and locally ablative therapies. However, not all patients with OMBC benefit from such treatment, while all experience toxicity. To explore biomarkers identifying patients with OMBC and potential long-term survival, we compared tumor-immune characteristics of patients with OMBC and long-term versus shorter-term survival. MATERIALS AND METHODS: We collected tumor tissue of 97 patients with de novo OMBC (≤5 metastases) via the Dutch nationwide cancer and pathology registries using a case-control design. Long-term survivors (LTS) were defined as patients alive ≥10 years since OMBC diagnosis. Fifty-five LTS and 42 shorter-term survivors (STS) were included. Median follow-up was 15 years (IQR, 14-16). Tumor characteristics and infiltrating immune cells were assessed by immunohistochemistry and next-generation RNA-sequencing. Association of the resulting 52 biomarkers with long-term survival was assessed using logistic regression. Associations with survival within LTS were assessed using Cox-proportional hazards modeling. P values were adjusted for multiple hypothesis testing. RESULTS: Most patients had estrogen receptor (ER)–positive OMBC (n = 86; 89%) and 23 (24%) had human epidermal growth factor receptor 2–positive disease. ER positivity in primary tumors distinguished LTS from STS. In addition, extracellular matrix (ECM)2-low and ECM4-high distinguished between long-term and shorter-term survival. Immune levels in the primary tumor did not associate with LTS. However, within the LTS subset, higher immune levels associated with improved progression-free survival. CONCLUSION: We identified tumor and ECM features in the primary tumor of patients with de novo OMBC that were associated with long-term survival. Our data should be validated in other patients with OMBC before they can be used in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2023
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44. A living biobank of patient-derived ductal carcinoma in situ mouse-intraductal xenografts identifies risk factors for invasive progression

Author

Hutten, Stefan J, de Bruijn, Roebi, Lutz, Catrin, Badoux, Madelon, Eijkman, Timo, Chao, Xue, Ciwinska, Marta, Sheinman, Michael, Messal, Hendrik, Herencia-Ropero, Andrea, Kristel, Petra, Mulder, Lennart, van der Waal, Rens, Sanders, Joyce, Almekinders, Mathilde M, Llop-Guevara, Alba, Davies, Helen R, van Haren, Matthijs J, Martin, Nathaniel I, Behbod, Fariba, Nik-Zainal, Serena, Serra, Violeta, van Rheenen, Jacco, Lips, Esther H, Wessels, Lodewyk FA, Grand Challenge PRECISION Consortium, Jelle, Wesseling, Jelle, Scheele, Colinda LGJ, and Jonkers, Jos

Subjects
biobank, Cancer Research, Oncology, DCIS, overtreatment, in vivo, patient-derived models, risk factors, progression, MIND
Abstract

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC). Due to a lack of biomarkers able to distinguish high- from low-risk cases, DCIS is treated similar to early IBC even though the minority of untreated cases eventually become invasive. Here, we characterized 115 patient-derived mouse-intraductal (MIND) DCIS models reflecting the full spectrum of DCIS observed in patients. Utilizing the possibility to follow the natural progression of DCIS combined with omics and imaging data, we reveal multiple prognostic factors for high-risk DCIS including high grade, HER2 amplification, expansive 3D growth, and high burden of copy number aberrations. In addition, sequential transplantation of xenografts showed minimal phenotypic and genotypic changes over time, indicating that invasive behavior is an intrinsic phenotype of DCIS and supporting a multiclonal evolution model. Moreover, this study provides a collection of 19 distributable DCIS-MIND models spanning all molecular subtypes. ispartof: CANCER CELL vol:41 issue:5 pages:986-+ ispartof: location:United States status: published

Published
2023

46. Abstract PR006: A living biobank of patient-derived ductal carcinoma in situ (DCIS) Mouse-INtraDuctal (MIND) xenografts identifies multiple risk factors of invasive progression

Author

Hutten, Stefan J., primary, de Bruijn, Roebi, additional, Lutz, Catrin, additional, Badoux, Madelon, additional, Eijkman, Timo, additional, Chao, Xue, additional, Ciwinska, Marta, additional, Herencia-Ropero, Andrea, additional, Kristel, Petra, additional, Mulder, Lennart, additional, Sanders, Joyce, additional, Almekinders, Mathilde, additional, Llop-Gueverra, Alba, additional, Davies, Helen R., additional, Behbod, Fariba, additional, Nik-Zainal, Serena, additional, Serra, Violeta, additional, van Rheenen, Jacco, additional, Lips, Esther H., additional, Wessels, Lodewyk F.A., additional, Wesseling, Jelle, additional, Scheele, Colinda, additional, and Jonkers, Jos, additional

Published
2022
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47. Abstract PR002: Genomic predictor can discriminate between high- and low-risk DCIS

Author

Escorza, Maria Roman, primary, Sheinman, Michael, additional, Bismeijer, Tycho, additional, Ahmed, Ahmed A., additional, Shah, Vandna, additional, Marks, Jeffrey R., additional, King, Lorraine M., additional, Megalios, Anargyros, additional, Visser, Lindy L., additional, Hoogstrat, Marlous, additional, Davies, Helen R., additional, Kumar, Tapsi, additional, Collyar, Deborah, additional, Stobart, Hilary, additional, Pinder, Sarah, additional, Navin, Nicholas N., additional, Futreal, Andrew, additional, Nik-Zainal, Serena, additional, Hwang, E. Shelley, additional, Lips, Esther H., additional, Thompson, Alastair, additional, Wessels, Lodewyk F.A., additional, Wesseling, Jelle, additional, and Sawyer, Elinor J., additional

Published
2022
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49. Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

Author

Lips, Esther H, Kumar, Tapsi, Megalios, Anargyros, Visser, Lindy L, Sheinman, Michael, Fortunato, Angelo, Shah, Vandna, Hoogstraat, Marlous, Sei, Emi, Mallo, Diego, Roman-Escorza, Maria, Ahmed, Ahmed A, Xu, Mingchu, Van Den Belt-Dusebout, Alexandra W, Brugman, Wim, Casasent, Anna K, Clements, Karen, Davies, Helen R, Fu, Liping, Grigoriadis, Anita, Hardman, Timothy M, King, Lorraine M, Krete, Marielle, Kristel, Petra, De Maaker, Michiel, Maley, Carlo C, Marks, Jeffrey R, Menegaz, Brian A, Mulder, Lennart, Nieboer, Frank, Nowinski, Salpie, Pinder, Sarah, Quist, Jelmar, Salinas-Souza, Carolina, Schaapveld, Michael, Schmidt, Marjanka K, Shaaban, Abeer M, Shami, Rana, Sridharan, Mathini, Zhang, John, Stobart, Hilary, Collyar, Deborah, Nik-Zainal, Serena, Wessels, Lodewyk FA, Hwang, E Shelley, Navin, Nicholas E, Futreal, P Andrew, Grand Challenge PRECISION Consortium, Thompson, Alastair M, Wesseling, Jelle, Sawyer, Elinor J, Lips, Esther H [0000-0003-3488-4935], Kumar, Tapsi [0000-0003-2825-3387], Megalios, Anargyros [0000-0002-7363-5184], Visser, Lindy L [0000-0001-7856-1981], Hoogstraat, Marlous [0000-0002-4916-1177], Mallo, Diego [0000-0002-9046-8859], Roman-Escorza, Maria [0000-0002-6259-5025], Ahmed, Ahmed A [0000-0002-0409-7589], Clements, Karen [0000-0003-0113-4409], Grigoriadis, Anita [0000-0003-3434-201X], Maley, Carlo C [0000-0002-0745-7076], Menegaz, Brian A [0000-0002-3020-5790], Pinder, Sarah [0000-0003-4167-8910], Shaaban, Abeer M [0000-0001-5784-8705], Collyar, Deborah [0000-0003-0886-0964], Nik-Zainal, Serena [0000-0001-5054-1727], Wessels, Lodewyk FA [0000-0002-1656-6995], Navin, Nicholas E [0000-0002-2106-8624], Futreal, P Andrew [0000-0001-8663-2671], Wesseling, Jelle [0000-0002-8940-2676], Sawyer, Elinor J [0000-0001-8285-4111], and Apollo - University of Cambridge Repository

Subjects
Carcinoma, Ductal, Breast, article, Breast Neoplasms, 631/67/1347, Genomics, 631/208/514/1948, body regions, Carcinoma, Intraductal, Noninfiltrating, Biomarkers, Tumor, Humans, Female, Neoplasm Recurrence, Local, skin and connective tissue diseases, neoplasms
Abstract

Funder: Career Development and Innovation Cancer Award, Guys & St Thomas’ Charity and the Cancer Research UK King’s Health Partners Centre at King’s College London., Funder: T32 Translational Genomics Fellowship (NIH), Funder: Single Cell Genomics CPRIT Core Facilities Grant (RP180684)., Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.

Published
2022
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50. Microcalcification crystallography as a potential marker of DCIS recurrence.

Author

Gosling, Sarah B., Arnold, Emily L., Davies, Samantha K., Cross, Hannah, Bouybayoune, Ihssane, Calabrese, Doriana, Nallala, Jayakrupakar, Pinder, Sarah E., Fu, Liping, Lips, Esther H., King, Lorraine, Marks, Jeffrey, Hall, Allison, Grimm, Lars J., Lynch, Thomas, Pinto, Donna, Stobart, Hilary, Hwang, E. Shelley, Wesseling, Jelle, and Geraki, Kalotina

Subjects
CALCIFICATIONS of the breast, CALCIUM ions, CANCER invasiveness, CANCER relapse, PROGNOSIS, CRYSTALLOGRAPHY
Abstract

Ductal carcinoma in-situ (DCIS) accounts for 20–25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation. [ABSTRACT FROM AUTHOR]

Published
2023
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