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1. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

Author: Braybrooke, Jeremy, Bradley, Rosie, Gray, Richard, Hills, Robert K, Pan, Hongchao, Peto, Richard, Dodwell, David, McGale, Paul, Taylor, Carolyn, Aihara, Tomohiko, Anderson, Stewart, Blum, Joanne, Cardoso, Fatima, Chen, Xiaosong, Crown, John P, Ejlertsen, Bent, Friedl, Thomas W P, Harbeck, Nadia, Janni, Wolfgang, Jensen, Maj-Britt, Mamounas, Eleftherios, Narui, Kazutaka, Nitz, Ulrike, Norton, Larry, O'Shaughnessy, Joyce, Piccart, Martine, Robert, Nicholas, Shao, Zhi-Ming, Slamon, Dennis, Sparano, Joseph, Watanabe, Toru, Yothers, Greg, Yu, Ke-Da, Berry, Richard, Boddington, Clare, Clarke, Mike, Davies, Christina, Davies, Lucy, Duane, Fran, Evans, Vaughan, Gay, Jo, Gettins, Lucy, Godwin, Jon, James, Sam, Lui, Hui, Lui, Zulian, MacKinnon, Elizabeth, Mannu, Gurdeep, McHugh, Theresa, Morris, Philip, Read, Simon, Straiton, Ewan, Buzdar, Aman, Suman, Vera J, Hunt, Kelly K, Leonard, Robert C F, Mansi, Janine, Delbaldo, Catherine, Piedbois, Pascal, Quinaux, Emmanuel, Fesl, Christian, Gnant, Michael, Sölkner, Lidija, Steger, Guenther, Eikesdal, Hans Petter, Lønning, Per Eystein, Bee, Valerie, Fung, Helena, Mackey, John, Martin, Miguel, Press, Michael, De Azambuja, Evandro, Gelber, Richard, Regan, Meredith, Di Leo, Angelo, Van Dooren, Veerle, Nogaret, Jean Marie, Bartlett, John, Chen, Bingshu E, Gelmon, Karen, Goss, Paul E, Levine, Mark N, Parulekar, Wendy, Pritchard, Kathleen I, Shepherd, Lois, Berry, Donald, Cirrincione, Constance, Shulman, Lawrence N, Winer, Eric, Gelman, Rebecca S, Harris, Jay R, Henderson, Craig, Shapiro, Charles L, Christiansen, Peer, Ewertz, Marianne, Mouridsen, Henning T, Van Leeuwen, Elise, Linn, Sabine, Van Rossum, Annelot G J, Van Tinteren, Harm, Van Werkhoven, Erik, Goldstein, Lori, Gray, Robert, Eiermann, Wolfgang, Gianni, Luca, Valagussa, Pinuccia, Bogaerts, Jan, Bonnefoi, Herve, Poncet, Coralie, Huovinen, Riikka, Joensuu, Heikki, Bonneterre, Jacques, Fargeot, Pierre, Fumoleau, Pierre, Kerbrat, Pierre, Luporsi, Elisabeth, Namer, Moïse, Carrasco, Eva M, Segui, Miguel Angel, Meisner, Christoph, Loibl, Sibylle, Nekljudova, Valentina, Thomssen, Christoph, Von Minckwitz, Gunter, Kümmel, Sherko, Lopez, Massimo, Vici, Patrizia, Fountzilas, George, Koliou, Georgia, Mavroudis, Dimitrios, Saloustros, Emmanouil, Brain, Etienne, Delaloge, Suzette, Michiels, Stefan, Mathoulin-Pelissier, Simone, Bines, Jose, Sarmento, Roberta M B, Bonadonna, Gianni, Brambilla, Cristina, Rossi, Anna, Bliss, Judith, Coombes, Raoul Charles, Kilburn, Lucy, Marty, Michel, Amadori, Dino, Boccardo, Francesco, Nanni, Oriana, Rubagotti, Alessandra, Scarpi, Emanuela, Masuda, Norikazu, Toi, Masakazu, Ueno, Takayuki, Ishikawa, Takashi, Matsumoto, Koji, Takao, Shintaro, Sommer, Harald, Foroglou, Pericles, Giokas, George, Kondylis, D, Lissaios, Byron, Reinisch, Mattea, Lee, Keun Seok, Nam, Byung-Ho, Ro, Jung Sil, De Matteis, Andrea, Perrone, Francesco, Tang, Gong, Wolmark, Norman, Hozumi, Yasuo, Nomura, Yasuo, Earl, Helena, Hiller, Louise, Vallier, Anne-Laure, De Mastro, Lucia, Venturini, Macro, Delozier, Thierry, Lemonnier, Jerome, Martin, Anne-Laure, Roché, Henri, Spielmann, Marc, Chen, Xiasong, Shen, Kunwei, Albain, Kathy, Barlow, William, Budd, George T, Gralow, Julie, Hayes, Dan, Bartlett-Lee, Peter, Ellis, Paul, Bianco, Angelo Raffaele, De Laurentiis, Michelino, De Placido, Sabino, Wildiers, Hans, Hsu, Limin, Eremin, Oleg, Walker, Leslie G, Ahlgren, Johan, Blomqvist, Carl, Holmberg, Lars, Lindman, Henrik, Asmar, Lina, Jones, Stephen E, Gluz, Oleg, Liedtke, Cornelia, Arriagada, Rodrigo, Bergsten-Nordström, Elizabeth, Carey, Lisa, Coleman, Robert, Cuzick, Jack, Davidson, Nancy, Dignam, James, Dowsett, Mitch, Francis, Prudence A, Goetz, Matthew P, Goodwin, Pam, Halpin-Murphy, Pat, Hill, Catherine, Jagsi, Reshma, Mukai, Hirofumi, Ohashi, Yasuo, Pierce, Lori, Poortmans, Philip, Raina, Vinod, Rea, Daniel, Robertson, John, Rutgers, Emiel, Salgado, Roberto, Spanic, Tanja, Tutt, Andrew, Viale, Giuseppe, Wang, Xiang, Whelan, Tim, Wilcken, Nicholas, Cameron, David, Bergh, Jonas, and Swain, Sandra M
Abstract: Anthracycline–taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline–taxane regimens.
Published: 2023
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2. Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

Author: Bamias, Aristotelis, Zakopoulou, Roubini, Tzannis, Kimon, Sakellakis, Minas, Koutsoukos, Konstantinos, Kyriazoglou, Anastasios, Panagiotou, Aikaterini, Armylagos, Stylianos, Rokas, Konstantinos, Gotzias, Dimitrios, Boulouta, Anna, Bozionelou, Vassiliki, Stravodimos, Konstantinos, Varkarakis, Ioannis, Mavroudis, Dimitrios, and Dimopoulos, Meletios-Athanasios
Abstract: Recently approved agents for post-vascular endothelial growth factor/post-vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors treatment of metastatic renal-cell carcinomas (mRCC), such as axitinib, nivolumab, and cabozantinib were shown to improve prognosis and substituted everolimus in this setting. We studied practice patterns, efficacy, and tolerability of these agents in a real-world series of Greek patients. We included patients with mRCC who received everolimus, axitinib, or nivolumab after progression on first-line anti-VEGF/VEGFRs therapy. Patients were stratified into three groups. Group A received nivolumab with or without cabozantinib at some point in their disease. Group B received axitinib but without nivolumab or cabozantinib. Group C received only everolimus among the four approved agents. Overall, 131 patients were included in the analysis. Everolimus and nivolumab were mainly used in the second line, while axitinib and cabozantinib were mostly used in the third and fourth lines. Median overall survival (OS) from first-line initiation was 8.7 [95% confidence interval (CI), 4–not reached], 3.6 (95% CI, 2–6), and 2.1 years (95% CI, 1.4–2.6) for Group A, B, and C, respectively (P < 0.001). Median OS from the initiation of second-line therapy was 3.5, 2.7, and 1.3 years, respectively (P < 0.001). There was no impact of first-line agent or treatment timing on survival. International Metastatic Renal Cell Carcinoma Database Consortium risk stratification was associated with OS. Toxicities observed were within expected frequencies. Grade ≥3 events were rare. Adoption of modern standards in everyday treatment of mRCC results in prolongation of survival. Real-world datasets are the new landmarks of survival for future research.
Published: 2023
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3. FANCMmissense variants and breast cancer risk: a case-control association study of 75,156 European women

Author: Figlioli, Gisella, Billaud, Amandine, Ahearn, Thomas U., Antonenkova, Natalia N., Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blok, Marinus J., Bogdanova, Natalia V., Bonanni, Bernardo, Burwinkel, Barbara, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Cessna, Melissa H., Chanock, Stephen J., Czene, Kamila, Devilee, Peter, Dörk, Thilo, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A., Figueroa, Jonine D., Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, González-Neira, Anna, Grassmann, Felix, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harrington, Patricia A., He, Wei, Hillemanns, Peter, Hollestelle, Antoinette, Hooning, Maartje J., Hoppe, Reiner, Howell, Anthony, Humphreys, Keith, Jager, Agnes, Jakubowska, Anna, Khusnutdinova, Elza K., Ko, Yon-Dschun, Kristensen, Vessela N., Lindblom, Annika, Lissowska, Jolanta, Lubiński, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Mavroudis, Dimitrios, Newman, William G., Obi, Nadia, Panayiotidis, Mihalis I., Rashid, Muhammad U., Rhenius, Valerie, Rookus, Matti A., Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sironen, Reijo, Southey, Melissa C., Suvanto, Maija, Tollenaar, Rob A. E. M., Tomlinson, Ian, Truong, Thérèse, van der Kolk, Lizet E., van Veen, Elke M., Wappenschmidt, Barbara, Yang, Xiaohong R., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Easton, Douglas F., Lush, Michael, Michailidou, Kyriaki, Pharoah, Paul D. P., Wang, Qin, Adank, Muriel A., Schmidt, Marjanka K., Andrulis, Irene L., Chang-Claude, Jenny, Nevanlinna, Heli, Chenevix-Trench, Georgia, Evans, D. Gareth, Milne, Roger L., Radice, Paolo, and Peterlongo, Paolo
Abstract: Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCMconfer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCMmissense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCMMVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07–2.04; P= 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCMMVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08–1.38; P= 0.002). Our results support the definition from previous analyses of FANCMas a moderate-risk breast cancer gene and provide evidence that FANCMMVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCMMVs.
Published: 2023
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4. Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

Author: Levi, Hagai, Carmi, Shai, Rosset, Saharon, Yerushalmi, Rinat, Zick, Aviad, Yablonski-Peretz, Tamar, Wang, Qin, Bolla, Manjeet K, Dennis, Joe, Michailidou, Kyriaki, Lush, Michael, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Arndt, Volker, Augustinsson, Annelie, Auvinen, Pa¨ivi, Beane Freeman, Laura, Beckmann, Matthias, Behrens, Sabine, Bermisheva, Marina, Bodelon, Clara, Bogdanova, Natalia V, Bojesen, Stig E, Brenner, Hermann, Byers, Helen, Camp, Nicola, Castelao, Jose, Chang-Claude, Jenny, Chirlaque, María-Dolores, Chung, Wendy, Clarke, Christine, Collee, Margriet J, Colonna, Sarah, Couch, Fergus, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary, Devilee, Peter, Dork, Thilo, Dossus, Laure, Eccles, Diana M, Eliassen, A. Heather, Eriksson, Mikael, Evans, Gareth, Fasching, Peter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Garcia-Saenz, Jose Angel, Genkinger, Jeanine, Giles, Graham G, Goldberg, Mark, Guénel, Pascal, Hall, Per, Hamann, Ute, He, Wei, Hillemanns, Peter, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John, Jakovchevska, Simona, Jakubowska, Anna, Jernstro¨m, Helena, John, Esther, Johnson, Nichola, Jones, Michael, Vijai, Joseph, Kaaks, Rudolf, Khusnutdinova, Elza, Kitahara, Cari, Koutros, Stella, Kristensen, Vessela, Kurian, Allison W, Lacey, James, Lambrechts, Diether, Le Marchand, Loic, Lejbkowicz, Flavio, Lindblom, Annika, Loibl, Sibylle, Lori, Adriana, Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Mavroudis, Dimitrios, Menon, Usha, Mulligan, AnnaMarie, Murphy, Rachel, Nevelsteen, Ines, Newman, William G, Obi, Nadia, O'Brien, Katie, Offit, Ken, Olshan, Andrew, Plaseska-Karanfilska, Dijana, Olson, Janet, Panico, Salvatore, Park-Simon, Tjoung-Won, Patel, Alpa, Peterlongo, Paolo, Rack, Brigitte, Radice, Paolo, Rennert, Gad, Rhenius, Valerie, Romero, Atocha, Saloustros, Emmanouil, Sandler, Dale, Schmidt, Marjanka K, Schwentner, Lukas, Shah, Mitul, Sharma, Priyanka, Simard, Jacques, Southey, Melissa, Stone, Jennifer, Tapper, William J, Taylor, Jack, Teras, Lauren, Toland, Amanda E, Troester, Melissa, Truong, Thérèse, van der Kolk, Lizet E, Weinberg, Clarice, Wendt, Camilla, Yang, Xiaohong Rose, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M, Pharoah, Paul, Easton, Douglas F, Ben-Sachar, Shay, Elefant, Naama, Shamir, Ron, and Elkon, Ran
Abstract: BackgroundPolygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.MethodsWe generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.ResultsIn the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).ConclusionsExtant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
Published: 2023
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5. Intrameningioma metastasis: A case-based literature review.

Author: Papadakis, Benjamin Konstantinos, Vorrias, Eleftherios, Bräutigam, Konstantin, Chochlidakis, Nikolaos, Koutsopoulos, Anastasios, Mavroudis, Dimitrios, Vakis, Antonis, and Tsitsipanis, Christos
Abstract: • Tumor-to-tumor metastasis is rare. • "Tumor-to-tumor metastasis" and "collision tumor" are not synonymous. • Lung and breast cancer are frequent sites of origin. • Vascularisation, metabolic milieu, and tumor microenvironment predispose for host-recipient-interaction. A tumor-to-tumor metastasis inside a meningioma is a rare phenomenon. Malignant neoplasms of the breast and lung are the most common primary tumors. Other sites of origin include prostate, renal and gastric neoplasms. The included case files were retrieved from the medical records of the University Hospital of Crete, Greece. A review of the literature was conducted in March 2020 via PubMed. Relevant search results were few. We report a case of a 66-year-old female, with known Small Cell Lung Cancer, who presented with left-sided hemiparesis. The Magnetic Resonance Imaging scan revealed a right frontal extra-axial mass. The patient underwent a craniotomy and a gross total removal of the tumor. Histological examination of the excised mass revealed metastatic adenocarcinoma deposits inside a meningioma: tumor-to-tumor metastasis. Reviewing the available literature, it has been hypothesized that the following factors play a role in the pathophysiology of this phenomenon: progesterone and estrogen receptors, cell-to-cell adhesion molecules, rich vascularization, favorable metabolic, micro-and immunological environment. Meningiomas seem to be the most common type of intracranial neoplasm to host a metastasis. There is a difference between tumor-to-tumor metastasis and collision tumors. The former implies a recipient role of the host tumor, and the latter refers to a co-localization of two different tumors that grow into one another, both being in the same organ. Tumor-to-tumor brain metastasis is a well-described phenomenon but with unclear pathophysiology. Deeper knowledge could be beneficial for its management. [ABSTRACT FROM AUTHOR]
Published: 2021
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6. Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

Author: Dixon-Suen, Suzanne C, Lewis, Sarah J, Martin, Richard M, English, Dallas R, Boyle, Terry, Giles, Graham G, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Lush, Michael, Investigators, ABCTB, Ahearn, Thomas U, Ambrosone, Christine B, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Auvinen, Pa¨ivi, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brenner, Hermann, Bru¨ning, Thomas, Buys, Saundra S, Camp, Nicola J, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Cessna, Melissa H, Chang-Claude, Jenny, Chanock, Stephen J, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Do¨rk, Thilo, Dwek, Miriam, Eccles, Diana M, Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Goldberg, Mark S, Guénel, Pascal, Gu¨ndert, Melanie, Hahnen, Eric, Haiman, Christopher A, Ha¨berle, Lothar, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N, Harvie, Michelle, Hillemanns, Peter, Hollestelle, Antoinette, Hooning, Maartje J, Hoppe, Reiner, Hopper, John, Howell, Anthony, Hunter, David J, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, Lacey, James V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Loibl, Sibylle, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, Menon, Usha, Mulligan, Anna Marie, Murphy, Rachel A, Collaborators, NBCS, Nevanlinna, Heli, Nevelsteen, Ines, Newman, William G, Offit, Kenneth, Olshan, Andrew F, Olsson, Håkan, Orr, Nick, Patel, Alpa, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Radice, Paolo, Rees-Punia, Erika, Rennert, Gad, Rennert, Hedy S, Romero, Atocha, Saloustros, Emmanouil, Sandler, Dale P, Schmidt, Marjanka K, Schmutzler, Rita K, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C, Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J, Tamimi, Rulla M, Tapper, William J, Taylor, Jack A, Terry, Mary Beth, Tollenaar, Rob A E M, Troester, Melissa A, Truong, Thérèse, Untch, Michael, Vachon, Celine M, Joseph, Vijai, Wappenschmidt, Barbara, Weinberg, Clarice R, Wolk, Alicja, Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M, Pharoah, Paul D P, Easton, Douglas F, Milne, Roger L, and Lynch, Brigid M
Abstract: ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105–377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
Published: 2022
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7. Endovascular Treatment of Malignant Superior Vena Cava Syndrome through Upper-Limb Access: A Comparison between Venous-Dedicated and Conventional Stents.

Author: Matthaiou, Nikolas, Galanakis, Nikolaos, Kehagias, Elias, Kontopodis, Nikolaos, Charalambous, Stavros, Kholcheva, Nelly, Tsetis, Konstantinos, Mavroudis, Dimitrios, and Tsetis, Dimitrios
Abstract: Purpose: To retrospectively evaluate the technical and clinical outcomes of superior vena cava (SVC) stent placement through upper-limb venous access in malignant SVC syndrome (SVCS) and compare the efficacy of different nitinol stent types.Materials and Methods: Between 2006 and 2018, 156 patients (132 male; mean age, 62 y; age range, 33-81 y) underwent SVC stent placement for malignant obstructions through upper-limb venous access with 1 of 3 types of nitinol stent: 1 venous-dedicated (Sinus-XL stent) and 2 non-venous-dedicated (E-Luminexx Vascular Stent and Protégé GPS). Cases of common femoral vein access or non-nitinol stents were excluded from further analysis. The mean duration of follow-up was 8 mo.Results: Technical success was achieved in 99.3% of cases. One patient died during the procedure as a result of cardiac tamponade. Balloon predilation was performed in 10 patients and postdilation in 126. Mean procedural time was 34.4 min (range, 18-80 min). Overall survival rates were 92.3%, 57.3%, and 26.8%, and overall primary patency rates were 94.5%, 84.8% and 79.6%, at 1, 6, and 12 mo, respectively. There were no statistically significant differences in primary patency rates between venous- and non-venous-dedicated stents or among different Stanford SVCS grading groups (P > .05).Conclusions: SVC stent placement through an upper-limb approach is a safe, fast, and effective technique. There is no evident benefit of venous-dedicated vs non-venous-dedicated stents in the treatment of malignant SVCS. [ABSTRACT FROM AUTHOR]
Published: 2020
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8. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author: Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R., Allen, Jamie, Kar, Siddhartha, Pooley, Karen A., Dennis, Joe, Michailidou, Kyriaki, Turman, Constance, Soucy, Penny, Lemaçon, Audrey, Lush, Michael, Tyrer, Jonathan P., Ghoussaini, Maya, Moradi Marjaneh, Mahdi, Jiang, Xia, Agata, Simona, Aittomäki, Kristiina, Alonso, M. Rosario, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J., Arun, Banu K., Auber, Bernd, Auer, Paul L., Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Amie M., Blomqvist, Carl, Blot, William, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Borg, Ake, Bosse, Kristin, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brock, Ian W., Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A., Camp, Nicola J., Campbell, Ian, Canzian, Federico, Carroll, Jason S., Carter, Brian D., Castelao, Jose E., Chiquette, Jocelyne, Christiansen, Hans, Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collée, J. Margriet, Cornelissen, Sten, Couch, Fergus J., Cox, Angela, Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian S., Domchek, Susan M., Dörk, Thilo, dos-Santos-Silva, Isabel, Droit, Arnaud, Dubois, Stéphane, Dumont, Martine, Duran, Mercedes, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Fletcher, Olivia, Floris, Giuseppe, Flyger, Henrik, Foretova, Lenka, Foulkes, William D., Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Gambino, Gaetana, Ganz, Patricia A., Gapstur, Susan M., Garber, Judy, García-Sáenz, José A., Gaudet, Mia M., Georgoulias, Vassilios, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Tibiletti, Maria Grazia, Greene, Mark H., Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hartikainen, Jaana M., Hartman, Mikael, He, Wei, Healey, Catherine S., Heemskerk-Gerritsen, Bernadette A. M., Heyworth, Jane, Hillemanns, Peter, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hooning, Maartje J., Hopper, John L., Howell, Anthony, Huang, Guanmengqian, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Iwasaki, Motoki, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jankowitz, Rachel C., John, Esther M., Johnson, Nichola, Jones, Michael E., Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Kerin, Michael J., Khusnutdinova, Elza, Kiiski, Johanna I., Kirk, Judy, Kitahara, Cari M., Ko, Yon-Dschun, Konstantopoulou, Irene, Kosma, Veli-Matti, Koutros, Stella, Kubelka-Sabit, Katerina, Kwong, Ava, Kyriacou, Kyriacos, Laitman, Yael, Lambrechts, Diether, Lee, Eunjung, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Lindblom, Annika, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lubiński, Jan, MacInnis, Robert J., Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Mayes, Rebecca, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Miller, Nicola, Montagna, Marco, Moreno, Fernando, Muir, Kenneth, Mulligan, Anna Marie, Muñoz-Garzon, Victor M., Muranen, Taru A., Narod, Steven A., Nassir, Rami, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Nielsen, Finn C., Nikitina-Zake, Liene, Norman, Aaron, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olsson, Håkan, Orr, Nick, Osorio, Ana, Pankratz, V. Shane, Papp, Janos, Park, Sue K., Park-Simon, Tjoung-Won, Parsons, Michael T., Paul, James, Pedersen, Inge Sokilde, Peissel, Bernard, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Prokofyeva, Darya, Pujana, Miquel Angel, Pylkäs, Katri, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rau-Murthy, Rohini, Rennert, Gad, Risch, Harvey A., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sánchez-Herrero, Estela, Sandler, Dale P., Santamariña, Marta, Saunders, Christobel, Sawyer, Elinor J., Scheuner, Maren T., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schöttker, Ben, Schürmann, Peter, Scott, Christopher, Scott, Rodney J., Senter, Leigha, Seynaeve, Caroline M., Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Singer, Christian F., Slavin, Thomas P., Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Spurdle, Amanda B., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony J., Tamimi, Rulla M., Tan, Yen Yen, Tapper, William J., Taylor, Jack A., Teixeira, Manuel R., Tengström, Maria, Teo, Soo Hwang, Terry, Mary Beth, Teulé, Alex, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Torres-Mejía, Gabriela, Troester, Melissa A., Truong, Thérèse, Tung, Nadine, Tzardi, Maria, Ulmer, Hans-Ulrich, Vachon, Celine M., van Asperen, Christi J., van der Kolk, Lizet E., van Rensburg, Elizabeth J., Vega, Ana, Viel, Alessandra, Vijai, Joseph, Vogel, Maartje J., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yannoukakos, Drakoulis, Zhang, Yan, Zheng, Wei, Hunter, David, Pharoah, Paul D. P., Chang-Claude, Jenny, García-Closas, Montserrat, Schmidt, Marjanka K., Milne, Roger L., Kristensen, Vessela N., French, Juliet D., Edwards, Stacey L., Antoniou, Antonis C., Chenevix-Trench, Georgia, Simard, Jacques, Easton, Douglas F., Kraft, Peter, and Dunning, Alison M.
Abstract: Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
Published: 2020
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9. Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.

Author: Papadakis, Georgios Z., Mavroudis, Dimitrios, Georgoulias, Vasilios, Souglakos, John, Alegakis, Athanasios K., Samonis, George, Bagci, Ulas, Makrigiannakis, Antonis, and Zoras, Odysseas
Abstract: Objective Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. Design 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS). Results Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho = 0.361, p < 0.001) with each other, while presenting significant differences across age groups (all p values < 0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p = 0.558) or after completion (p = 0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p = 0.487) or after (p = 0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p = 0.499; OS: p = 0.220) or IGFBP-3 (DFI: p = 0.900; OS: p = 0.406) serum levels. Conclusions IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer. [ABSTRACT FROM AUTHOR]
Published: 2017
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10. Efficacy and safety results by age in monarchE: Adjuvant abemaciclib combined with endocrine therapy (ET) in patients with HR+, HER2-, node-positive, high-risk early breast cancer (EBC).

Author: Hamilton, Erika P., Kim, Jee Hyun, Eigeliene, Natalja, Mavroudis, Dimitrios, Median, Dragos Mircea, Marconato, Heloisa, Shevnia, Serhii, Ozyilkan, Ozgur, Puig, Juan Manuel, Shannon, Catherine M., Munoz, Maria, San Antonio, Belén, Wei, Ran, O'Shaughnessy, Joyce, Johnston, Stephen R. D., and Guarneri, Valentina
Published: 2023
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11. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author: Wu, Lang, Shi, Wei, Long, Jirong, Guo, Xingyi, Michailidou, Kyriaki, Beesley, Jonathan, Bolla, Manjeet, Shu, Xiao-Ou, Lu, Yingchang, Cai, Qiuyin, Al-Ejeh, Fares, Rozali, Esdy, Wang, Qin, Dennis, Joe, Li, Bingshan, Zeng, Chenjie, Feng, Helian, Gusev, Alexander, Barfield, Richard, Andrulis, Irene, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan, Auer, Paul, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia, Bojesen, Stig, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara, Burwinkel, Barbara, Caldés, Trinidad, Canzian, Federico, Carter, Brian, Castelao, J., Chang-Claude, Jenny, Chen, Xiaoqing, Cheng, Ting-Yuan, Christiansen, Hans, Clarke, Christine, Collée, Margriet, Cornelissen, Sten, Couch, Fergus, Cox, David, Cox, Angela, Cross, Simon, Cunningham, Julie, Czene, Kamila, Daly, Mary, Devilee, Peter, Doheny, Kimberly, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Eccles, Diana, Eilber, Ursula, Eliassen, A., Engel, Christoph, Eriksson, Mikael, Fachal, Laura, Fasching, Peter, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan, García-Closas, Montserrat, Gaudet, Mia, Ghoussaini, Maya, Giles, Graham, Goldberg, Mark, Goldgar, David, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hollestelle, Antoinette, Hoover, Robert, Hopper, John, Huang, Guanmengqian, Humphreys, Keith, Hunter, David, Jakubowska, Anna, Janni, Wolfgang, John, Esther, Johnson, Nichola, Jones, Kristine, Jones, Michael, Jung, Audrey, Kaaks, Rudolf, Kerin, Michael, Khusnutdinova, Elza, Kosma, Veli-Matti, Kristensen, Vessela, Lambrechts, Diether, Marchand, Loic, Li, Jingmei, Lindström, Sara, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Lubinski, Jan, Luccarini, Craig, Lux, Michael, MacInnis, Robert, Maishman, Tom, Kostovska, Ivana, Mannermaa, Arto, Manson, JoAnn, Margolin, Sara, Mavroudis, Dimitrios, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Meyer, Jeffery, Mulligan, Anna, Neuhausen, Susan, Nevanlinna, Heli, Neven, Patrick, Nielsen, Sune, Nordestgaard, Børge, Olopade, Olufunmilayo, Olson, Janet, Olsson, Håkan, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Prentice, Ross, Presneau, Nadege, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rennert, Gad, Rennert, Hedy, Rhenius, Valerie, Romero, Atocha, Romm, Jane, Rudolph, Anja, Saloustros, Emmanouil, Sandler, Dale, Sawyer, Elinor, Schmidt, Marjanka, Schmutzler, Rita, Schneeweiss, Andreas, Scott, Rodney, Scott, Christopher, Seal, Sheila, Shah, Mitul, Shrubsole, Martha, Smeets, Ann, Southey, Melissa, Spinelli, John, Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony, Tamimi, Rulla, Tapper, William, Taylor, Jack, Terry, Mary, Tessier, Daniel, Thomas, Abigail, Thöne, Kathrin, Tollenaar, Rob, Torres, Diana, Truong, Thérèse, Untch, Michael, Vachon, Celine, Berg, David, Vincent, Daniel, Waisfisz, Quinten, Weinberg, Clarice, Wendt, Camilla, Whittemore, Alice, Wildiers, Hans, Willett, Walter, Winqvist, Robert, Wolk, Alicja, Xia, Lucy, Yang, Xiaohong, Ziogas, Argyrios, Ziv, Elad, Dunning, Alison, Pharoah, Paul, Simard, Jacques, Milne, Roger, Edwards, Stacey, Kraft, Peter, Easton, Douglas, Chenevix-Trench, Georgia, and Zheng, Wei
Abstract: The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P< 5.82 × 10−6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology. A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.
Published: 2018
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12. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Author: Milne, Roger L, Kuchenbaecker, Karoline B, Michailidou, Kyriaki, Beesley, Jonathan, Kar, Siddhartha, Lindström, Sara, Hui, Shirley, Lemaçon, Audrey, Soucy, Penny, Dennis, Joe, Jiang, Xia, Rostamianfar, Asha, Finucane, Hilary, Bolla, Manjeet K, McGuffog, Lesley, Wang, Qin, Aalfs, Cora M, Adams, Marcia, Adlard, Julian, Agata, Simona, Ahmed, Shahana, Ahsan, Habibul, Aittomäki, Kristiina, Al-Ejeh, Fares, Allen, Jamie, Ambrosone, Christine B, Amos, Christopher I, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Auber, Bernd, Auer, Paul L, Ausems, Margreet G E M, Azzollini, Jacopo, Bacot, François, Balmaña, Judith, Barile, Monica, Barjhoux, Laure, Barkardottir, Rosa B, Barrdahl, Myrto, Barnes, Daniel, Barrowdale, Daniel, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Bignon, Yves-Jean, Blazer, Kathleen R, Blok, Marinus J, Blomqvist, Carl, Blot, William, Bobolis, Kristie, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Anders, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Bozsik, Aniko, Bradbury, Angela R, Brand, Judith S, Brauch, Hiltrud, Brenner, Hermann, Bressac-de Paillerets, Brigitte, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Brunet, Joan, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byun, Jinyoung, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canzian, Federico, Caron, Olivier, Carracedo, Angel, Carter, Brian D, Castelao, J Esteban, Castera, Laurent, Caux-Moncoutier, Virginie, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Xiaoqing, Cheng, Ting-Yuan David, Chiquette, Jocelyne, Christiansen, Hans, Claes, Kathleen B M, Clarke, Christine L, Conner, Thomas, Conroy, Don M, Cook, Jackie, Cordina-Duverger, Emilie, Cornelissen, Sten, Coupier, Isabelle, Cox, Angela, Cox, David G, Cross, Simon S, Cuk, Katarina, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Damiola, Francesca, Darabi, Hatef, Davidson, Rosemarie, De Leeneer, Kim, Devilee, Peter, Dicks, Ed, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Doheny, Kimberly F, Domchek, Susan M, Dorfling, Cecilia M, Dörk, Thilo, dos-Santos-Silva, Isabel, Dubois, Stéphane, Dugué, Pierre-Antoine, Dumont, Martine, Dunning, Alison M, Durcan, Lorraine, Dwek, Miriam, Dworniczak, Bernd, Eccles, Diana, Eeles, Ros, Ehrencrona, Hans, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Fachal, Laura, Faivre, Laurence, Fasching, Peter A, Faust, Ulrike, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foulkes, William D, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Gaddam, Pragna, Gammon, Marilie D, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, Garcia-Barberan, Vanesa, García-Sáenz, José A, Gaudet, Mia M, Gauthier-Villars, Marion, Gehrig, Andrea, Georgoulias, Vassilios, Gerdes, Anne-Marie, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Goodfellow, Paul, Greene, Mark H, Alnæs, Grethe I Grenaker, Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Gschwantler-Kaulich, Daphne, Guénel, Pascal, Guo, Qi, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hallberg, Emily, Hamann, Ute, Hamel, Nathalie, Hankinson, Susan, Hansen, Thomas V O, Harrington, Patricia, Hart, Steven N, Hartikainen, Jaana M, Healey, Catherine S, Hein, Alexander, Helbig, Sonja, Henderson, Alex, Heyworth, Jane, Hicks, Belynda, Hillemanns, Peter, Hodgson, Shirley, Hogervorst, Frans B, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Bob, Hopper, John L, Hu, Chunling, Huang, Guanmengqian, Hulick, Peter J, Humphreys, Keith, Hunter, David J, Imyanitov, Evgeny N, Isaacs, Claudine, Iwasaki, Motoki, Izatt, Louise, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Janni, Wolfgang, Jensen, Uffe Birk, John, Esther M, Johnson, Nichola, Jones, Kristine, Jones, Michael, Jukkola-Vuorinen, Arja, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kang, Daehee, Kast, Karin, Keeman, Renske, Kerin, Michael J, Kets, Carolien M, Keupers, Machteld, Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna I, Kim, Sung-Won, Knight, Julia A, Konstantopoulou, Irene, Kosma, Veli-Matti, Kristensen, Vessela N, Kruse, Torben A, Kwong, Ava, Lænkholm, Anne-Vibeke, Laitman, Yael, Lalloo, Fiona, Lambrechts, Diether, Landsman, Keren, Lasset, Christine, Lazaro, Conxi, Le Marchand, Loic, Lecarpentier, Julie, Lee, Andrew, Lee, Eunjung, Lee, Jong Won, Lee, Min Hyuk, Lejbkowicz, Flavio, Lesueur, Fabienne, Li, Jingmei, Lilyquist, Jenna, Lincoln, Anne, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Long, Jirong, Loud, Jennifer T, Lubinski, Jan, Luccarini, Craig, Lush, Michael, MacInnis, Robert J, Maishman, Tom, Makalic, Enes, Kostovska, Ivana Maleva, Malone, Kathleen E, Manoukian, Siranoush, Manson, JoAnn E, Margolin, Sara, Martens, John W M, Martinez, Maria Elena, Matsuo, Keitaro, Mavroudis, Dimitrios, Mazoyer, Sylvie, McLean, Catriona, Meijers-Heijboer, Hanne, Menéndez, Primitiva, Meyer, Jeffery, Miao, Hui, Miller, Austin, Miller, Nicola, Mitchell, Gillian, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Mulot, Claire, Nadesan, Sue, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nevelsteen, Ines, Niederacher, Dieter, Nielsen, Sune F, Nordestgaard, Børge G, Norman, Aaron, Nussbaum, Robert L, Olah, Edith, Olopade, Olufunmilayo I, Olson, Janet E, Olswold, Curtis, Ong, Kai-ren, Oosterwijk, Jan C, Orr, Nick, Osorio, Ana, Pankratz, V Shane, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Lloyd, Rachel, Pedersen, Inge Søkilde, Peissel, Bernard, Peixoto, Ana, Perez, Jose I A, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M, Pinchev, Mila, Plaseska-Karanfilska, Dijana, Poppe, Bruce, Porteous, Mary E, Prentice, Ross, Presneau, Nadege, Prokofieva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rennert, Hedy S, Rhenius, Valerie, Rhiem, Kerstin, Richardson, Andrea, Rodriguez, Gustavo C, Romero, Atocha, Romm, Jane, Rookus, Matti A, Rudolph, Anja, Ruediger, Thomas, Saloustros, Emmanouil, Sanders, Joyce, Sandler, Dale P, Sangrajrang, Suleeporn, Sawyer, Elinor J, Schmidt, Daniel F, Schoemaker, Minouk J, Schumacher, Fredrick, Schürmann, Peter, Schwentner, Lukas, Scott, Christopher, Scott, Rodney J, Seal, Sheila, Senter, Leigha, Seynaeve, Caroline, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Sheng, Xin, Shimelis, Hermela, Shrubsole, Martha J, Shu, Xiao-Ou, Side, Lucy E, Singer, Christian F, Sohn, Christof, Southey, Melissa C, Spinelli, John J, Spurdle, Amanda B, Stegmaier, Christa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Surowy, Harald, Sutter, Christian, Swerdlow, Anthony, Szabo, Csilla I, Tamimi, Rulla M, Tan, Yen Y, Taylor, Jack A, Tejada, Maria-Isabel, Tengström, Maria, Teo, Soo H, Terry, Mary B, Tessier, Daniel C, Teulé, Alex, Thöne, Kathrin, Thull, Darcy L, Tibiletti, Maria Grazia, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E, Tollenaar, Rob A E M, Tomlinson, Ian, Tong, Ling, Torres, Diana, Tranchant, Martine, Truong, Thérèse, Tucker, Kathy, Tung, Nadine, Tyrer, Jonathan, Ulmer, Hans-Ulrich, Vachon, Celine, van Asperen, Christi J, Van Den Berg, David, van den Ouweland, Ans M W, van Rensburg, Elizabeth J, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Viel, Alessandra, Vijai, Joseph, Vincent, Daniel, Vollenweider, Jason, Walker, Lisa, Wang, Zhaoming, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weinberg, Clarice R, Weitzel, Jeffrey N, Wendt, Camilla, Wesseling, Jelle, Whittemore, Alice S, Wijnen, Juul T, Willett, Walter, Winqvist, Robert, Wolk, Alicja, Wu, Anna H, Xia, Lucy, Yang, Xiaohong R, Yannoukakos, Drakoulis, Zaffaroni, Daniela, Zheng, Wei, Zhu, Bin, Ziogas, Argyrios, Ziv, Elad, Zorn, Kristin K, Gago-Dominguez, Manuela, Mannermaa, Arto, Olsson, Håkan, Teixeira, Manuel R, Stone, Jennifer, Offit, Kenneth, Ottini, Laura, Park, Sue K, Thomassen, Mads, Hall, Per, Meindl, Alfons, Schmutzler, Rita K, Droit, Arnaud, Bader, Gary D, Pharoah, Paul D P, Couch, Fergus J, Easton, Douglas F, Kraft, Peter, Chenevix-Trench, Georgia, García-Closas, Montserrat, Schmidt, Marjanka K, Antoniou, Antonis C, and Simard, Jacques
Abstract: Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
Published: 2017
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13. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Author: Petrylak, Daniel P, de Wit, Ronald, Chi, Kim N, Drakaki, Alexandra, Sternberg, Cora N, Nishiyama, Hiroyuki, Castellano, Daniel, Hussain, Syed, Fléchon, Aude, Bamias, Aristotelis, Yu, Evan Y, van der Heijden, Michiel S, Matsubara, Nobuaki, Alekseev, Boris, Necchi, Andrea, Géczi, Lajos, Ou, Yen-Chuan, Coskun, Hasan Senol, Su, Wen-Pin, Hegemann, Miriam, Percent, Ivor J, Lee, Jae-Lyun, Tucci, Marcello, Semenov, Andrey, Laestadius, Fredrik, Peer, Avivit, Tortora, Giampaolo, Safina, Sufia, del Muro, Xavier Garcia, Rodriguez-Vida, Alejo, Cicin, Irfan, Harputluoglu, Hakan, Widau, Ryan C, Liepa, Astra M, Walgren, Richard A, Hamid, Oday, Zimmermann, Annamaria H, Bell-McGuinn, Katherine M, Powles, Thomas, Wong, Suet-Lai Shirley, Tan, Thean Hsiang, Hovey, Elizabeth Jane, Clay, Timothy Dudley, Ng, Siobhan Su Wan, Rutten, Annemie, Machiels, Jean-Pascal, Dumez, Herlinde, Cheng, Susanna Yee-Shan, Chi, Kim Nguyen, Ferrario, Cristiano, Sengeloev, Lisa, Jensen, Niels Viggo, Thibault, Constance, Laguerre, Brigitte, Laestadius, Fredrik, Joly, Florence, Flechon, Aude, Culine, Stéphane, Becht, Catherine, Niegisch, Günter, Stöckle, Michael, Grimm, Marc-Oliver, Gakis, Georgios, Schultze-Seemann, Wolfgang, Kalofonos, Haralambos, Mavroudis, Dimitrios, Papandreou, Christos, Karavasilis, Vasilis, Bamias, Aristotelis, Révész, Janos, Geczi, Lajos, Rosenbaum, Eli, Leibowitz-Amit, Raya, Kejzman, Daniel, Peer, Avivit, Sarid, David, Scagliotti, Giorgio Vittorio, Sternberg, Cora N, Tortora, Giampaolo, Bracarda, Sergio, Necchi, Andrea, Massari, Francesco, Osawa, Takahiro, Miyajima, Naoto, Shinohara, Nobuo, Fukuta, Fumimasa, Ohyama, Chikara, Obara, Wataru, Yamashita, Shinichi, Tomita, Yoshihiko, Kawai, Koji, Fukasawa, Satoshi, Matsubara, Nobuaki, Oyama, Masafumi, Yonese, Junji, Nagata, Masayoshi, Uemura, Motohide, Nishimura, Kazuo, Kawakita, Mutsushi, Tsunemori, Hiroyuki, Hashine, Katsuyoshi, Inokuchi, Junichi, Yokomizo, Akira, Nagamori, Satoshi, Lee, Jae-Lyun, Lee, Hyo Jin, Park, Se Hoon, Rha, Sun Young, Kim, Yu Jung, Lee, Yun-Gyoo, Cortés, Leticia Vazquez, Flores, Claudia Lorena Urzua, Blaisse, Reinoud J B, van der Heijden, Michiel S, de Wit, Ronald, Erdkamp, Fransiscus L G, Aarts, Maureen J B, Wojcik-Tomaszewska, Joanna, Tomczak, Piotr, Sikora-Kupis, Bozena, Schenker, Michael, Herzal, Alina Amalia, Udrea, Anghel Adrian, Karlov, Petr, Safina, Sufia Z, Alekseev, Boris, Semenov, Andrey, Fomkin, Roman, Pulido, Enrique Grande, Del Muro, F Xavier García, Mignorance, Juan Ignacio Delgado, Gauna, Daniel Castellano, Rodríguez-Vida, Alejo, Su, Yu-Li, Ou, Yen-Chuan, Lin, Chien-Liang, Su, Wen-Pin, Lin, Chia-Chi, Yeh, Su-Peng, Çiçin, Irfan, Harputluoglu, Hakan, Erman, Mustafa, Coskun, Hasan Senol, Urun, Yuksel, Golovko, Yurii, Bondarenko, Igor, Sinielnikov, Ivan, Powles, Thomas, Crabb, Simon, Syndikus, Isabel, Huddart, Robert, Sundar, Santhanam, Chowdhury, Simon, Sarwar, Naveed, Drakaki, Alexandra, Flaig, Thomas, Pan, Chong Xian, Petrylak, Daniel, Schwarz, James, Percent, Ivor, Cultrera, Jennifer, Hainsworth, John, Herms, Benjamin, Lawler, William, Lowe, Thomas, Tagawa, Scott, Aragon-Ching, Jeanny, and Vaishampayan, Ulka
Abstract: Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population.
Published: 2017
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14. Detection of KRASExon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RASWild Type Metastatic Colorectal Cancer

Author: Matikas, Alexios, Voutsina, Alexandra, Lagoudaki, Eleni, Hatzidaki, Dora, Trypaki, Maria, Stoupis, Giannis, Tzardi, Maria, Mavroudis, Dimitrios, and Georgoulias, Vasilios
Abstract: INTRODUCTION:The presence of KRASmutations in patients with metastatic colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR. Even in patients with RASwild type (WT) tumors, resistance eventually develops due to multiple mechanisms, including the expansion of previously undetected KRASmutated clones. In this feasibility study, we aimed to detect KRASexon 2 mutations in serial samples of circulating tumor cells (CTCs) of RASWT patients with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET) system. METHODS:CTC isolation using the ISET system was performed from prospectively collected blood samples obtained from patients with RASand BRAFWT mCRC prior to first-line therapy initiation, at first imaging assessment and on disease progression. CTCs were enumerated using hematoxylin & eosin and CD45 double stain on a single membrane spot. DNA was extracted from 5 spots and KRASexon 2 mutations were detected using a custom quantitative Polymerase Chain Reaction (qPCR) assay. RESULTS:Fifteen patients were enrolled and 28 blood samples were analyzed. In 9 (60%) patients, at least one sample was positive for the presence of a KRASexon 2 mutation. In 11 out of 28 samples (39.2%) with detectable CTCs a KRASmutation was detected; the corresponding percentages for baseline and on progression samples were 27% and 37.5%, respectively. The most commonly detected mutations were G13D and G12C (n=3). The presence of KRASmutated CTCs at baseline was not prognostic for either PFS (P=.950) or OS (P=.383). CTC kinetics did not follow tumor response patterns. CONCLUSION:The results demonstrate that using a qPCR-based assay, KRASexon 2 mutations could be detected in CTCs captured by the ISET system from patients with RASWT primary tumors. However, the clinical relevance of these CTCs remains to be determined in future studies.
Published: 2017
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15. Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group (HGUCG)

Author: Bamias, Aristotle, Peroukidis, Stavros, Stamatopoulou, Sophia, Tzannis, Kimon, Koutsoukos, Konstantinos, Andreadis, Charalambos, Bozionelou, Vasiliki, Pistalmatzian, Nikos, Papatsoris, Athanasios, Stravodimos, Konstantinos, Varthalitis, Ioannis, Karamouzis, Michalis, Milaki, Georgia, Agorastos, Antonios, Kentepozidis, Nikos, Androulakis, Nikos, Bompolaki, Iliada, Kalofonos, Haralampos, Mavroudis, Dimitrios, and Dimopoulos, Meletios A.
Abstract: Advanced urothelial cancer (AUCa) is associated with poor long-term survival due to nonexposure to cisplatin-based chemotherapy and poor outcome after relapse. This study records the patterns of practice in AUCa, focusing on first-line treatment and management of relapsed disease.
Published: 2016
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16. Immunohistochemical study of pElk-1 expression in human breast cancer: Association with breast cancer biologic profile and clinicopathologic features.

Author: Laliotis, Aggelos, Vrekoussis, Thomas, Kafousi, Maria, Sanidas, Elias, Askoxilakis, John, Melissas, John, Mavroudis, Dimitrios, Castanas, Elias, and Stathopoulos, Efstathios N.
Subjects: BREAST cancer, IMMUNOHISTOCHEMISTRY, TRANSCRIPTION factors, CYCLINS, GENE expression, LYMPH node cancer, METASTASIS
Abstract: Abstract: Background: Recently an increased interest on Elk1 protein and its role in breast cancer evolution has been noted. This protein is an element of the Ets family of transcription factors and it has been involved in a number of important cell processes through the activation of different genes, in a number of normal tissues as well as in many malignancies. Methods: One hundred and seventy (n = 170) cases of operable breast cancer (invasive ductal, lobular and mixed type breast carcinomas) were randomly selected and investigated for the expression of pElk-1, Ki-67 and Cyclin D1 using immunohistochemistry. Our findings were correlated with tumors'' clinicopathologic data and biologic profile. Results: Activated Elk1 is positively associated with ER (p-value: 0.018) and also shows a positive association of with Cyclin D1 (p-value: <0.001). No relationship was noted between pElk1 and Ki67 (p-value: 0.213). Luminal A and B Her-2 negative breast cancer subtypes were showing greater pElk-1 immunoreactivity compared to Her-2 and Basal breast cancer subtypes, and also a higher staining intensity. No association of the molecule with other clinicopathologic characteristics (tumor size, stage, histological type or lymph node metastases) or disease adverse events (local recurrence, metastasis or death) was evidenced. Conclusions: Our findings offer a new perspective for the role of pElk-1 in breast neoplasia suggesting a direct relation of this molecule to tumor biology and a putative target of personalized breast cancer therapies, although its prognostic/discriminant role is not supported. [Copyright &y& Elsevier]
Published: 2013
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17. Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: A systematic review and meta-analysis.

Author: Valachis, Antonis, Mauri, Davide, Polyzos, Nikolaos P., Chlouverakis, Grigoris, Mavroudis, Dimitrios, and Georgoulias, Vassilios
Subjects: BREAST cancer treatment, TRASTUZUMAB, CANCER chemotherapy, HER2 gene, SYSTEMATIC reviews, META-analysis, ADJUVANT treatment of cancer
Abstract: Abstract: Purpose: To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer. Methods: Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, breast-conserving surgery (BCS) rate and toxicity. Results: Five trials were identified with 515 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm (RR 1.85, 95% CI: 1.39–2.46; p-value < 0.001). No significant difference in terms of breast-conserving surgery between the two treatment arms was observed (OR: 0.98, 95% CI: 0.80–1.19, p-value = 0.82). Regarding toxicity, the addition of trastuzumab did not increase the incidence of neutropenia, neutropenic fever, and cardiac adverse events. Conclusion: The addition of trastuzumab in HER2-positive breast cancer in the neoadjuvant setting improves the probability of achieving higher pCR with no additional toxicity. Based on the available evidence, the use of trastuzumab combined with neoadjuvant chemothetherapy in patients with HER2-positive breast cancer seems to offer substantial benefit in terms of pCR. [Copyright &y& Elsevier]
Published: 2011
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18. Association analysis identifies 65 new breast cancer risk loci

Author: Michailidou, Kyriaki, Lindström, Sara, Dennis, Joe, Beesley, Jonathan, Hui, Shirley, Kar, Siddhartha, Lemaçon, Audrey, Soucy, Penny, Glubb, Dylan, Rostamianfar, Asha, Bolla, Manjeet K., Wang, Qin, Tyrer, Jonathan, Dicks, Ed, Lee, Andrew, Wang, Zhaoming, Allen, Jamie, Keeman, Renske, Eilber, Ursula, French, Juliet D., Qing Chen, Xiao, Fachal, Laura, McCue, Karen, McCart Reed, Amy E., Ghoussaini, Maya, Carroll, Jason S., Jiang, Xia, Finucane, Hilary, Adams, Marcia, Adank, Muriel A., Ahsan, Habibul, Aittomäki, Kristiina, Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Arun, Banu, Auer, Paul L., Bacot, François, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brock, Ian W., Broeks, Annegien, Brooks-Wilson, Angela, Brucker, Sara Y., Brüning, Thomas, Burwinkel, Barbara, Butterbach, Katja, Cai, Qiuyin, Cai, Hui, Caldés, Trinidad, Canzian, Federico, Carracedo, Angel, Carter, Brian D., Castelao, Jose E., Chan, Tsun L., David Cheng, Ting-Yuan, Seng Chia, Kee, Choi, Ji-Yeob, Christiansen, Hans, Clarke, Christine L., Collée, Margriet, Conroy, Don M., Cordina-Duverger, Emilie, Cornelissen, Sten, Cox, David G., Cox, Angela, Cross, Simon S., Cunningham, Julie M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Doheny, Kimberly F., Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Ellberg, Carolina, Elvira, Mingajeva, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A., Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gaborieau, Valerie, Gabrielson, Marike, Gago-Dominguez, Manuela, Gao, Yu-Tang, Gapstur, Susan M., García-Sáenz, José A., Gaudet, Mia M., Georgoulias, Vassilios, Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Grenaker Alnæs, Grethe I., Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hamel, Nathalie, Hankinson, Susan, Harrington, Patricia, Hart, Steven N., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Heyworth, Jane, Hicks, Belynda, Hillemanns, Peter, Ho, Dona N., Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Hou, Ming-Feng, Hsiung, Chia-Ni, Huang, Guanmengqian, Humphreys, Keith, Ishiguro, Junko, Ito, Hidemi, Iwasaki, Motoki, Iwata, Hiroji, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Johnson, Nichola, Jones, Kristine, Jones, Michael, Jukkola-Vuorinen, Arja, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kang, Daehee, Kasuga, Yoshio, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna I., Kim, Sung-Won, Knight, Julia A., Kosma, Veli-Matti, Kristensen, Vessela N., Krüger, Ute, Kwong, Ava, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lee, Min Hyuk, Lee, Jong Won, Neng Lee, Chuen, Lejbkowicz, Flavio, Li, Jingmei, Lilyquist, Jenna, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Long, Jirong, Lophatananon, Artitaya, Lubinski, Jan, Luccarini, Craig, Lux, Michael P., Ma, Edmond S. K., MacInnis, Robert J., Maishman, Tom, Makalic, Enes, Malone, Kathleen E., Kostovska, Ivana Maleva, Mannermaa, Arto, Manoukian, Siranoush, Manson, JoAnn E., Margolin, Sara, Mariapun, Shivaani, Martinez, Maria Elena, Matsuo, Keitaro, Mavroudis, Dimitrios, McKay, James, McLean, Catriona, Meijers-Heijboer, Hanne, Meindl, Alfons, Menéndez, Primitiva, Menon, Usha, Meyer, Jeffery, Miao, Hui, Miller, Nicola, Taib, Nur Aishah Mohd, Muir, Kenneth, Mulligan, Anna Marie, Mulot, Claire, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Nielsen, Sune F., Noh, Dong-Young, Nordestgaard, Børge G., Norman, Aaron, Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Håkan, Olswold, Curtis, Orr, Nick, Pankratz, V. Shane, Park, Sue K., Park-Simon, Tjoung-Won, Lloyd, Rachel, Perez, Jose I. A., Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Pinchev, Mila, Plaseska-Karanfilska, Dijana, Prentice, Ross, Presneau, Nadege, Prokofyeva, Darya, Pugh, Elizabeth, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rennert, Gadi, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Romm, Jane, Ruddy, Kathryn J., Rüdiger, Thomas, Rudolph, Anja, Ruebner, Matthias, Rutgers, Emiel J. T., Saloustros, Emmanouil, Sandler, Dale P., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schumacher, Fredrick, Schürmann, Peter, Scott, Rodney J., Scott, Christopher, Seal, Sheila, Seynaeve, Caroline, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Sheng, Grace, Sherman, Mark E., Shrubsole, Martha J., Shu, Xiao-Ou, Smeets, Ann, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stegmaier, Christa, Stewart-Brown, Sarah, Stone, Jennifer, Stram, Daniel O., Surowy, Harald, Swerdlow, Anthony, Tamimi, Rulla, Taylor, Jack A., Tengström, Maria, Teo, Soo H., Beth Terry, Mary, Tessier, Daniel C., Thanasitthichai, Somchai, Thöne, Kathrin, Tollenaar, Rob A. E. M., Tomlinson, Ian, Tong, Ling, Torres, Diana, Truong, Thérèse, Tseng, Chiu-Chen, Tsugane, Shoichiro, Ulmer, Hans-Ulrich, Ursin, Giske, Untch, Michael, Vachon, Celine, van Asperen, Christi J., Van Den Berg, David, van den Ouweland, Ans M. W., van der Kolk, Lizet, van der Luijt, Rob B., Vincent, Daniel, Vollenweider, Jason, Waisfisz, Quinten, Wang-Gohrke, Shan, Weinberg, Clarice R., Wendt, Camilla, Whittemore, Alice S., Wildiers, Hans, Willett, Walter, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Xia, Lucy, Yamaji, Taiki, Yang, Xiaohong R., Har Yip, Cheng, Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Zheng, Ying, Zhu, Bin, Ziogas, Argyrios, Ziv, Elad, Lakhani, Sunil R., Antoniou, Antonis C., Droit, Arnaud, Andrulis, Irene L., Amos, Christopher I., Couch, Fergus J., Pharoah, Paul D. P., Chang-Claude, Jenny, Hall, Per, Hunter, David J., Milne, Roger L., García-Closas, Montserrat, Schmidt, Marjanka K., Chanock, Stephen J., Dunning, Alison M., Edwards, Stacey L., Bader, Gary D., Chenevix-Trench, Georgia, Simard, Jacques, Kraft, Peter, and Easton, Douglas F.
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10−8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
Published: 2017
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19. Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes

Author: Mavaddat, Nasim, Dorling, Leila, Carvalho, Sara, Allen, Jamie, González-Neira, Anna, Keeman, Renske, Bolla, Manjeet K., Dennis, Joe, Wang, Qin, Ahearn, Thomas U., Andrulis, Irene L., Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Stig E., Briceno, Ignacio, Brüning, Thomas, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Christiansen, Hans, Czene, Kamila, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Geisler, Jürgen, Giles, Graham G., Guénel, Pascal, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Hartikainen, Jaana M., Hartman, Mikael, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza K., Kristensen, Vessela N., Li, Jingmei, Lim, Swee Ho, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubinski, Jan, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Mohd Taib, Nur Aishah, Morra, Anna, Muir, Kenneth, Obi, Nadia, Osorio, Ana, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C., Thorne, Heather, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Yip, Cheng Har, Spurdle, Amanda B., Vreeswijk, Maaike P.G., Dunning, Alison M., García-Closas, Montserrat, Pharoah, Paul D.P., Kvist, Anders, Muranen, Taru A., Nevanlinna, Heli, Teo, Soo Hwang, Devilee, Peter, Schmidt, Marjanka K., and Easton, Douglas F.
Abstract: IMPORTANCE: Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction. OBJECTIVE: To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies. DESIGN, SETTING, AND PARTICIPANTS: The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021. EXPOSURES: Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53. MAIN OUTCOMES AND MEASURES: The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes. RESULTS: The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2− high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ERBB2+ and HR–ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger. CONCLUSIONS AND RELEVANCE: The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies.
Published: 2022
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20. Comparison of HER2 Detection Methods Between Central and Regional Laboratories in Greece

Author: Papadopoulos, Savvas, Kouvatseas, George, Skarlos, Dimosthenis, Malamos, Nikolaos, Delliou, Eleftheria, Saratsiotou, Ioanna, Ardavanis, Alexandros, Mavroudis, Dimitrios, Skarpidi, Evangelia, Arapantoni, Petroula, Karyda, Irini, Patakioyta, Frideriki, Aravantinos, Gerasimos, Razis, Evangelia, Fountzilas, George, and Kosmidis, Paris
Abstract: HER2 gene amplification and overexpression is associated with aggressive breast cancer and poor prognosis. Accurate HER2 testing of patients with breast cancer before treatment is important to ensure that as many patients with HER2-positive breast cancer as possible receive the most appropriate treatment and that women with HER2-negative disease avoid a potentially toxic therapy. This study compares immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) HER2 testing at central and regional laboratories in Greece.
Published: 2007
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21. Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by the Hellenic Cooperative Oncology Group

Author: Fountzilas, George, Pectasides, Dimitrios, Kalogera-Fountzila, Anna, Skarlos, Dimosthenis, Kalofonos, Haralambos P., Papadimitriou, Christos, Bafaloukos, Dimitrios, Lambropoulos, Stefanos, Papadopoulos, Savvas, Kourea, Helen, Markopoulos, Christos, Linardou, Helen, Mavroudis, Dimitrios, Briasoulis, Evangelos, Pavlidis, Nicholaos, Razis, Evangelia, Kosmidis, Paraskevas, and Gogas, Helen
Abstract: Summary Paclitaxel (TaxolR) and carboplatin are an effective combination regimen for treating advanced breast cancer. Gefitinib (IRESSA) is the first epidermal growth factor receptor tyrosine kinase inhibitor to be approved for cancer treatment. This multicenter phase II trial treated 68 patients with advanced breast cancer with paclitaxel (175 mg/m2 over 3 h) and 3-weekly carboplatin (area under the curve of 6) for six cycles, and 250 mg/day gefitinib orally. Median age was 57 (range 35–77) years, patients had performance status 0 (69.1%), 1 (27.9%) 2 (2.9%), 82.4% of patients had visceral metastases and 63.2% had received adjuvant chemotherapy. Forty-eight (70.6%) patients completed six cycles of chemotherapy and 20 (29.4%) patients discontinued treatment (seven [10.3%] due to disease progression, seven [10.3%] due to toxicity, five [7.4%] withdrew consent and one [1.5%] died after the first cycle). Sixty-three (92.7%) patients were evaluable for response; nine (13.2%) had complete responses, 30 (44.1%) had partial responses, 21 (30.9%) had stable disease and three (4.4%) had disease progression. Grade 3/4 adverse events in =5% of patients except of alopecia, included neutropenia (17.7%), anemia (10.3%), diarrhea (7.4%), thrombocytopenia (5.9%) and peripheral neuropathy (5.9%). Of those tumor biopsies available for immunohistochemical analysis (n=60), 5.0% were positive and 35.0% negative for expression of all HER-family receptors. Comparable numbers of tumor biopsies were nuclear p27kipl positive and negative (39.7 and 42.7%, respectively), with the majority (72.1%) negative for cytoplasmic p27kipl. The observed efficacy data in this study were similar to those reported for the combination of paclitaxel and carboplatin alone.
Published: 2005
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22. Continuation of Trastuzumab Beyond Disease Progression Is Feasible and Safe in Patients with Metastatic Breast Cancer: A Retrospective Analysis of 80 Cases by the Hellenic Cooperative Oncology Group

Author: Fountzilas, George, Razis, Evangelia, Tsavdaridis, Dimitrios, Karina, Maria, Labropoulos, Stefanos, Christodoulou, Christos, Mavroudis, Dimitrios, Gogas, Helen, Georgoulias, Vassilios, and Skarlos, Dimosthenis
Abstract: Despite the widespread use of trastuzumab in the management of patients with HER2-overexpressing metastatic breast cancer, its optimal duration of administration is unknown. We retrospectively reviewed the medical records of 80 such patients who received trastuzumab monotherapy or combination chemotherapy beyond disease progression in order to register their clinical course. Median age of the patients was 54 years. Ninety-one percent had 3+ HER2 overexpression and 9% had 2+ HER2 overexpression. Fifty-six percent of patients had previously been treated with chemotherapy for advanced disease. The most commonly used combinations in first- and second-line treatments were trastuzumab with paclitaxel and trastuzumab with vinorelbine, respectively. In total, 32 responses were observed, most of them during the second or third line of treatment. Severe toxicities frequently seen (in ≥ 5% of patients) were neutropenia (25%), thrombocytopenia (11.5%), infection (10%), peripheral neuropathy (9%), nausea/vomiting (6%), stomatitis (6%), diarrhea (6%), constipation (6%), edema (6%), and myalgias/arthralgias (5%). Median survival from diagnosis of advanced disease was 43.4 months (range, 6.4–91.7+), whereas median survival from disease progression after trastuzumab administration was 22.2 months (range, 0.01-32.9+). In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic breast cancer is feasible and safe. Randomized studies are warranted.
Published: 2003
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23. Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in patients with solid tumors

Author: Souglakos, John, Kotsakis, Athanaslos, Kouroussis, Charalambos, Kakolyris, Stylianos, Mavroudis, Dimitrios, Kalbakis, Konstadinos, Agelaki, Sofia, Vlachonikolis, John, Georgoulias, Vassilis, and Samonis, George
Abstract: Docetaxel is associated with severe lymphopenia and increased incidence of nonneutropenic infection. This study investigated the incidence of nonneutropenic infections and/or febrile episodes in patients with solid tumors receiving frontline docetaxel-based chemotherapy. Chemotherapy-naive patients with solid tumors treated with docetaxel-based chemotherapy were studied prospectively for the development of nonneutropenic infections. During a 2-year period, 680 cancer patients enrolled in 24 protocols received 2867 cycles of docetaxel-containing chemotherapy. Fifty-three patients (7.8%) developed nonneutropenic infections and/or febrile episodes. The most common of these were pulmonary infections (n = 25), Pneumocystis carinii interstitial pneumonias (n = 5), and candidal (n =11), herpetic (n =4), and cytomegaloviral (n =3) infections. Thirty-six patients (68%) had severe lymphopenia (< 900 cells per deciliter) and 49 (92%) had less than 400 CD4⁺ cells per deciliter. Patients with a low CD4⁺ cell count (≤ 200 cells per deciliter) had a significantly higher probability to develop opportunistic than common infections (P = 0.002). The incidence of nonneutropenic infections and/or febrile episodes was significantly higher in patients treated with docetaxel/gemcitabine (18.3%; P = 0.0001) and docetaxel/CDDP (11.7%; P = 0.012) than in those treated with docetaxel alone (3.6%). Conversely, 175 patients who received 752 cycles of chemotherapy with paclitaxel-containing regimens and 410 patients who received 2174 cycles with nontaxane-based regimens developed 6 (3.4%; p=0.042) and 12 (3%; p=0.001) nonneutropenic infections, respectively. Less than 10% of the patients of the two latter groups were lymphopenic. The risk of nonneutropenic infection in patients receiving docetaxel-based chemotherapy was 2.38 and 2.8 times higher than in patients receiving paclitaxel and nontaxane-based chemotherapy, respectively. Patients treated with docetaxel-based chemotherapy are at increased risk of developing nonneutropenic infections. This may be related, at least partly, to severe postchemotherapy CD4⁺ lymphopenia. Cancer 2002;95:132633. © 2002 American Cancer Society. DOI 10.1002/cncr.10802
Published: 2002
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24. Molecular Epidemiology and Treatment Patterns of Patients With EGFR Exon 20-Mutant NSCLC in the Precision Oncology Era: The European EXOTIC Registry

Author: Mountzios, Giannis, Planchard, David, Metro, Giulio, Tsiouda, Dora, Prelaj, Arsela, Lampaki, Sofia, Shalata, Walid, Riudavets, Mariona, Christopoulos, Petros, Girard, Nicolas, Albarrán-Artahona, Víctor, Garcia Campelo, Rosario, Samitas, Konstantinos, Banna, Giuseppe Luigi, Boukovinas, Ioannis, Agbarya, Abed, Koumarianou, Anna, Perdikouri, Eleni-Isidora, Kosmidis, Paris, Linardou, Helena, Mauri, David, Mavroudis, Dimitrios, Athanasiadis, Ilias, Kalofonos, Haralambos, Xenidis, Nikolaos, Korantzis, Ippokratis, Ardavanis, Alexandros, Rallis, Grigorios, Bottiglieri, Achille, Efthymiadis, Konstantinos, Oikonomopoulos, Georgios, Kokkalis, Alexandros, Saloustros, Emmanouil, Tsoukalas, Nikolaos, Bartzi, Dimitra, Economopoulou, Panagiota, Psyrri, Amanda, Reck, Martin, and Lo Russo, Giuseppe
Abstract: Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking.
Published: 2022
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25. Cytotoxic T Lymphocytes Specific for a Nonpolymorphic Proteinase 3 Peptide Preferentially Inhibit Chronic Myeloid Leukemia Colony-Forming Units

Author: Molldrem, Jeffrey J., Clave, Emmanuel, Jiang, Yin Zheng, Mavroudis, Dimitrios, Raptis, Anastasios, Hensel, Nancy, Agarwala, Vaishali, and Barrett, A. John
Abstract: We previously showed that a peptide (PR1) derived from the primary granule enzyme proteinase 3 induced peptide specific cytotoxic T lymphocytes (CTL) in a normal HLA-A2.1+ individual. These CTL showed HLA-restricted cytotoxicity to myeloid leukemias (which overexpress proteinase 3). To further investigate their antileukemic potential, we studied the ability of PR1-specific CTL, derived from two HLA-A2.1+ normal individuals, to inhibit colony-forming unit granulocyte-macrophage (CFU-GM) from normal and leukemic individuals. CTL from 20 day PR1 peptide-pulsed lymphocyte cultures showed 89% to 98% HLA-A2.1–restricted colony inhibition of chronic myeloid leukemia targets. Colony formation in normal HLA-A2.1+ bone marrow or HLA-A2.1- CML cells was not inhibited. Sequencing of the exon encoding PR1 showed that colony inhibition was not caused by polymorphic differences in proteinase 3 between effectors and targets. Analysis by flow cytometry showed that proteinase 3 was overexpressed in the leukemia targets compared with normal marrow targets (median channel fluorescence 1,399 v 298, P = .009). These results show that PR1-specific allogeneic T cells preferentially inhibit leukemic CFU-GM based on overexpression of proteinase 3, and that proteinase 3-specific CTL could be used for leukemia-specific adoptive immunotherapy.
Published: 1997
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26. CD34+Cell Dose Predicts Survival, Posttransplant Morbidity, and Rate of Hematologic Recovery After Allogeneic Marrow Transplants for Hematologic Malignancies

Author: Mavroudis, Dimitrios, Read, Elizabeth, Cottier-Fox, Michele, Couriel, Daniel, Molldrem, Jeffrey, Carter, Charles, Yu, Monica, Dunbar, Cynthia, and Barrett, John
Abstract: After autologous or allogeneic transplants of peripheral blood stem cells (PBSC), an adequate dose of CD34+cells is necessary to ensure early and sustained hematopoietic engraftment and favorable clinical outcome. There are no comparable data on the relationship between CD34+cell dose and recovery after allogeneic bone marrow transplants (BMT). Twenty-eight patients with hematologic malignancies received a BMT from an HLA-identical sibling, using T-cell depletion and cyclosporin for graft-versus-host disease prophylaxis and delayed donor lymphocyte transfusions in an attempt to prevent leukemia relapse. The treatment-related mortality (TRM), primarily due to infections and cytopenias, was significantly higher for 13 patients receiving less than 1 × 106CD34+cells/kg (64.9% ± 12.8% v6.9% ± 6.4%, P -.003). Survival at a median follow-up of 1 year was also lower in the group receiving less than 1 × 106CD34+cells/kg (30.8% ± 12.8 v74.3% ± 13.7%, P= .005). The CD34+cell dose was the only variable significantly associated with TRM. The dose of CD34+ cells also correlated with speed of hematopoietic recovery. Patients receiving more than 2 × 106CD34+cells/kg showed significantly earlier recovery of monocytes and a trend for earlier recovery of lymphocytes. They achieved platelet and red blood cell transfusion independence earlier, required less granulocyte colony-stimulating factor support during ganciclovir treatment, and spent fewer days in the hospital after transplantation. These results suggest that, for allogeneic T-cell-depleted BMT, the higher CD34+cell doses may improve outcome in engrafting patients.
Published: 1996
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27. The graftversusleukemia effect

Author: Mavroudis, Dimitrios and Barrett, John
Abstract: Although the graftversusleukemia effect was predicted from animal experiments almost 40 years ago, only recently has its role in clinical bone marrow transplantation become better defined. The graftversusleukemia effect was initially considered to be a minor component of the graftversushost reaction. However, more recent analyses of clinical bone marrow transplants and the successful treatment of relapsed leukemia with donor lymphocyte transfusions indicate that the graftversusleukemia effect can be very powerful and to some degree independent of graftversushost disease. Results of donor lymphocyte transfusions draw attention to wide variability in response according to the nature of the relapsed leukemia and also to additional therapies that may enhance the efficacy of donor lymphocyte transfusions. Although natural killer lymphocytes may play a role in the graftversusleukemia effect, attention is focusing increasingly on T lymphocytes as potent mediators of the effect. Both CD4and CD8cells, together with the cytokines they produce, can interact with leukemia cells to deliver a cytotoxic hit on the malignant clone. Although leukemia cells undoubtedly share common antigens with other tissues of the recipient resulting in nonspecific graftversushost and graftversusleukemia reactions, there is also the possibility that distinct antigens are presented to T cells by the leukemia cells, providing a basis for separating the graftversusleukemia from graftversushost reactions. The current clinical challenge is to devise strategies for separating the graftversusleukemia response from graftversushost disease.
Published: 1996

28. Salmonella enterica pneumonia in a patient with lung cancer.

Author: Samonis, George, Maraki, Sofia, Kouroussis, Charalambos, Mavroudis, Dimitrios, and Georgoulias, Vassilios
Abstract: A case of life-threatening Salmonella enterica serotype Enteritidis pneumonia in a febrile patient with lung cancer is described. The organism was isolated from the sputum, the protected specimen brush material of bronchial secretions, and the stool. Despite the early administration of appropriate and adequate treatment, the patient died 7 days after the onset of the infection.
Published: 2003

29. Salmonella entericaPneumonia in a Patient with Lung Cancer

Author: Samonis, George, Maraki, Sofia, Kouroussis, Charalambos, Mavroudis, Dimitrios, and Georgoulias, Vassilios
Abstract: ABSTRACTA case of life-threatening Salmonella entericaserotype Enteritidis pneumonia in a febrile patient with lung cancer is described. The organism was isolated from the sputum, the protected specimen brush material of bronchial secretions, and the stool. Despite the early administration of appropriate and adequate treatment, the patient died 7 days after the onset of the infection.
Published: 2003
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29 results on '"Mavroudis, Dimitrios"'

1. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

2. Outcomes from treatment of metastatic renal-cell carcinoma following failure of first-line anti-VEGF/VEGFR therapy: real-life evidence on the change of the treatment paradigm

3. FANCMmissense variants and breast cancer risk: a case-control association study of 75,156 European women

4. Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

5. Intrameningioma metastasis: A case-based literature review.

6. Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

7. Endovascular Treatment of Malignant Superior Vena Cava Syndrome through Upper-Limb Access: A Comparison between Venous-Dedicated and Conventional Stents.

8. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

9. Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.

10. Efficacy and safety results by age in monarchE: Adjuvant abemaciclib combined with endocrine therapy (ET) in patients with HR+, HER2-, node-positive, high-risk early breast cancer (EBC).

11. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

12. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

13. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

14. Detection of KRASExon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RASWild Type Metastatic Colorectal Cancer

15. Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group (HGUCG)

16. Immunohistochemical study of pElk-1 expression in human breast cancer: Association with breast cancer biologic profile and clinicopathologic features.

17. Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: A systematic review and meta-analysis.

18. Association analysis identifies 65 new breast cancer risk loci

19. Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes

20. Comparison of HER2 Detection Methods Between Central and Regional Laboratories in Greece

21. Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by the Hellenic Cooperative Oncology Group

22. Continuation of Trastuzumab Beyond Disease Progression Is Feasible and Safe in Patients with Metastatic Breast Cancer: A Retrospective Analysis of 80 Cases by the Hellenic Cooperative Oncology Group

23. Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in patients with solid tumors

24. Molecular Epidemiology and Treatment Patterns of Patients With EGFR Exon 20-Mutant NSCLC in the Precision Oncology Era: The European EXOTIC Registry

25. Cytotoxic T Lymphocytes Specific for a Nonpolymorphic Proteinase 3 Peptide Preferentially Inhibit Chronic Myeloid Leukemia Colony-Forming Units

26. CD34+Cell Dose Predicts Survival, Posttransplant Morbidity, and Rate of Hematologic Recovery After Allogeneic Marrow Transplants for Hematologic Malignancies

27. The graftversusleukemia effect

28. Salmonella enterica pneumonia in a patient with lung cancer.

29. Salmonella entericaPneumonia in a Patient with Lung Cancer

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