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2. Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact

Author

Garcia-Tejedor, Amparo, Falo, Catalina, Fernandez-Gonzalez, Sergi, Laplana, Maria, Gil-Gil, Miguel, Soler-Monso, Teresa, Martinez-Perez, Evelyn, Calvo, Iris, Calpelo, Hugo, Bajen, Maria-Teresa, Benitez, Ana, Ortega, Raul, Petit, Anna, Guma, Anna, Campos, Miriam, Stradella, Agostina, Lopez-Ojeda, Ana, Ponce, Jordi, Pla, Maria J., and Pernas, Sonia

Published
2023
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4. RANK is a poor prognosis marker and a therapeutic target in ER‐negative postmenopausal breast cancer

Author

Ciscar, Marina, Trinidad, Eva M, Perez‐Chacon, Gema, Alsaleem, Mansour, Jimenez, Maria, Jimenez‐Santos, Maria J, Perez‐Montoyo, Hector, Sanz‐Moreno, Adrian, Vethencourt, Andrea, Toss, Michael, Petit, Anna, Soler‐Monso, Maria T, Lopez, Victor, Gomez‐Miragaya, Jorge, Gomez‐Aleza, Clara, Dobrolecki, Lacey E, Lewis, Michael T, Bruna, Alejandra, Mouron, Silvana, Quintela‐Fandino, Miguel, Al‐Shahrour, Fatima, Martinez‐Aranda, Antonio, Sierra, Angels, Green, Andrew R, Rakha, Emad, and Gonzalez‐Suarez, Eva

Published
2023
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6. Modification of BRCA1-associated breast cancer risk by HMMR overexpression

Author

Mateo, Francesca, He, Zhengcheng, Mei, Lin, de Garibay, Gorka Ruiz, Herranz, Carmen, García, Nadia, Lorentzian, Amanda, Baiges, Alexandra, Blommaert, Eline, Gómez, Antonio, Mirallas, Oriol, Garrido-Utrilla, Anna, Palomero, Luis, Espín, Roderic, Extremera, Ana I., Soler-Monsó, M. Teresa, Petit, Anna, Li, Rong, Brunet, Joan, Chen, Ke, Tan, Susanna, Eaves, Connie J., McCloskey, Curtis, Hakem, Razq, Khokha, Rama, Lange, Philipp F., Lázaro, Conxi, Maxwell, Christopher A., and Pujana, Miquel Angel

Published
2022
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7. Author Correction: Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis.

Author

Zhang, Xiaowen, Chiang, Huai-Chin, Wang, Yao, Zhang, Chi, Smith, Sabrina, Zhao, Xiayan, Nair, Sreejith J, Michalek, Joel, Jatoi, Ismail, Lautner, Meeghan, Oliver, Boyce, Wang, Howard, Petit, Anna, Soler, Teresa, Brunet, Joan, Mateo, Francesca, Angel Pujana, Miguel, Poggi, Elizabeth, Chaldekas, Krysta, Isaacs, Claudine, Peshkin, Beth N, Ochoa, Oscar, Chedin, Frederic, Theoharis, Constantine, Sun, Lu-Zhe, Curiel, Tyler J, Elledge, Richard, Jin, Victor X, Hu, Yanfen, and Li, Rong

Abstract

This corrects the article DOI: 10.1038/ncomms15908.

Published
2018

8. Denosumab as an immune modulator in HER2-negative early breast cancer: results of the window-of-opportunity D-BIOMARK clinical trial.

Author

Vethencourt, Andrea, primary, Trinidad, Eva M., additional, Dorca, Eduard, additional, Petit, Anna, additional, Soler-Monsó, M. Teresa, additional, Ciscar, Marina, additional, Barranco, Alexandra, additional, Pérez-Chacón, Gema, additional, Jimenez, María, additional, Gomez-Aleza, Clara, additional, Purqueras, Elvira, additional, Hernández-Jiménez, Enrique, additional, Urruticoechea, Ander, additional, Morilla, Idoia, additional, Cachinero, Isaac, additional, García-Tejedor, Amparo, additional, Gil-Gil, Miguel, additional, Pernas, Sonia, additional, Falo, Catalina, additional, and Gonzalez-Suarez, Eva, additional

Published
2024
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9. Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis.

Author

Zhang, Xiaowen, Chiang, Huai-Chin, Wang, Yao, Zhang, Chi, Smith, Sabrina, Zhao, Xiayan, Nair, Sreejith J, Michalek, Joel, Jatoi, Ismail, Lautner, Meeghan, Oliver, Boyce, Wang, Howard, Petit, Anna, Soler, Teresa, Brunet, Joan, Mateo, Francesca, Angel Pujana, Miguel, Poggi, Elizabeth, Chaldekas, Krysta, Isaacs, Claudine, Peshkin, Beth N, Ochoa, Oscar, Chedin, Frederic, Theoharis, Constantine, Sun, Lu-Zhe, Curiel, Tyler J, Elledge, Richard, Jin, Victor X, Hu, Yanfen, and Li, Rong

Subjects
Breast, Animals, Mice, Knockout, Humans, Mice, Breast Neoplasms, RNA Polymerase II, RNA-Binding Proteins, Tumor Suppressor Proteins, BRCA1 Protein, Nuclear Proteins, Nucleic Acid Conformation, Female, Promoter Regions, Genetic, Carcinogenesis, Knockout, Promoter Regions, Genetic
Abstract

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.

Published
2017

10. The effect of omitting axillary dissection and the impact of radiotherapy on patients with breast cancer sentinel node macrometastases: a cohort study following the ACOSOG Z0011 and AMAROS trials

Author

Ortega Expósito, Carlos, Falo, Catalina, Pernas, Sonia, Pérez Carton, Samuel, Gil Gil, Miguel, Ortega, Raul, Pérez Montero, Héctor, Stradella, Agostina, Martinez, Evelyn, Laplana, Maria, Salinas, Sira, Luzardo, Ana, Soler, Teresa, Fernández Montoli, Maria Eulalia, Azcarate, Juan, Guma, Anna, Petit, Anna, Benitez, Ana, Bajen, Maite, Reyes Junca, Jose G., Campos, Miriam, Ruiz, Raquel, Ponce, Jordi, Pla, Maria J., and García Tejedor, Amparo

Published
2021
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11. Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

Author

Garcia-Tejedor, Amparo, Fernandez-Gonzalez, Sergi, Ortega, Raul, Gil-Gil, Miguel, Perez-Montero, Hector, Fernandez-Montolí, Eulalia, Stradella, Agostina, Recalde, Sabela, Soler, Teresa, Petit, Anna, Bajen, Maria Teresa, Benitez, Ana, Guma, Anna, Campos, Miriam, Pla, Maria J., Martinez, Evelyn, Laplana, Maria, Pernas, Sonia, Perez-Sildekova, Diana, Catala, Isabel, Ponce, Jordi, and Falo, Catalina

Published
2021
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12. AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer

Author

Kubli, Shawn P., Bassi, Christian, Roux, Cecilia, Wakeham, Andrew, Göbl, Christoph, Zhou, Wenjing, Jafari, Soode Moghadas, Snow, Bryan, Jones, Lisa, Palomero, Luis, Thu, Kelsie L., Cassetta, Luca, Soong, Daniel, Berger, Thorsten, Ramachandran, Parameswaran, Baniasadi, Shakiba P., Duncan, Gordon, Lindzen, Moshit, Yarden, Yosef, Herranz, Carmen, Lazaro, Conxi, Chu, Mandy F., Haight, Jillian, Tinto, Paul, Silvester, Jennifer, Cescon, David W., Petit, Anna, Pettersson, Sven, Pollard, Jeffrey W., Mak, Tak W., Pujana, Miguel A., Cappello, Paola, and Gorrini, Chiara

Published
2019

13. RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A., Green, Andrew R., Santamaria, Patricia G., Mulder, Celine, Lemeer, Simone, Arribas, Joaquin, Prat, Aleix, Puig, Teresa, and Gonzalez-Suarez, Eva

Published
2021
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14. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.

Author

Blanco, Ignacio, Kuchenbaecker, Karoline, Cuadras, Daniel, Wang, Xianshu, Barrowdale, Daniel, de Garibay, Gorka, Librado, Pablo, Sánchez-Gracia, Alejandro, Rozas, Julio, Bonifaci, Núria, McGuffog, Lesley, Pankratz, Vernon, Islam, Abul, Mateo, Francesca, Berenguer, Antoni, Petit, Anna, Català, Isabel, Brunet, Joan, Feliubadaló, Lidia, Tornero, Eva, Benítez, Javier, Osorio, Ana, Ramón y Cajal, Teresa, Nevanlinna, Heli, Aittomäki, Kristiina, Arun, Banu, Toland, Amanda, Karlan, Beth, Walsh, Christine, Lester, Jenny, Greene, Mark, Mai, Phuong, Nussbaum, Robert, Andrulis, Irene, Domchek, Susan, Nathanson, Katherine, Rebbeck, Timothy, Barkardottir, Rosa, Jakubowska, Anna, Lubinski, Jan, Durda, Katarzyna, Jaworska-Bieniek, Katarzyna, Claes, Kathleen, Van Maerken, Tom, Díez, Orland, Hansen, Thomas, Jønson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, de la Hoya, Miguel, Caldés, Trinidad, Dunning, Alison, Oliver, Clare, Fineberg, Elena, Cook, Margaret, Peock, Susan, McCann, Emma, Murray, Alex, Jacobs, Chris, Pichert, Gabriella, Lalloo, Fiona, Chu, Carol, Dorkins, Huw, Paterson, Joan, Ong, Kai-Ren, Teixeira, Manuel, Hogervorst, Frans, van der Hout, Annemarie, Seynaeve, Caroline, van der Luijt, Rob, Ligtenberg, Marjolijn, Devilee, Peter, Wijnen, Juul, Rookus, Matti, Meijers-Heijboer, Hanne, Blok, Marinus, van den Ouweland, Ans, Aalfs, Cora, Rodriguez, Gustavo, Phillips, Kelly-Anne, Piedmonte, Marion, Nerenstone, Stacy, Bae-Jump, Victoria, OMalley, David, Ratner, Elena, Schmutzler, Rita, Wappenschmidt, Barbara, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, and Varon-Mateeva, Raymonda

Subjects
Aurora Kinase A, Breast Neoplasms, Carcinogenesis, Cell Cycle Proteins, Estrogen Receptor alpha, Evolution, Molecular, Extracellular Matrix Proteins, Female, Genes, BRCA1, Genes, BRCA2, Genetic Loci, Genetic Predisposition to Disease, Humans, Hyaluronan Receptors, Likelihood Functions, Mammary Glands, Human, Microtubule-Associated Proteins, Mutation, Nuclear Proteins, Polymorphism, Single Nucleotide, Retrospective Studies, Tubulin
Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Published
2015

16. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.

Author

Maxwell, Christopher A, Benítez, Javier, Gómez-Baldó, Laia, Osorio, Ana, Bonifaci, Núria, Fernández-Ramires, Ricardo, Costes, Sylvain V, Guinó, Elisabet, Chen, Helen, Evans, Gareth JR, Mohan, Pooja, Català, Isabel, Petit, Anna, Aguilar, Helena, Villanueva, Alberto, Aytes, Alvaro, Serra-Musach, Jordi, Rennert, Gad, Lejbkowicz, Flavio, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Ripamonti, Carla B, Bonanni, Bernardo, Viel, Alessandra, Allavena, Anna, Bernard, Loris, Radice, Paolo, Friedman, Eitan, Kaufman, Bella, Laitman, Yael, Dubrovsky, Maya, Milgrom, Roni, Jakubowska, Anna, Cybulski, Cezary, Gorski, Bohdan, Jaworska, Katarzyna, Durda, Katarzyna, Sukiennicki, Grzegorz, Lubiński, Jan, Shugart, Yin Yao, Domchek, Susan M, Letrero, Richard, Weber, Barbara L, Hogervorst, Frans BL, Rookus, Matti A, Collee, J Margriet, Devilee, Peter, Ligtenberg, Marjolijn J, Luijt, Rob B van der, Aalfs, Cora M, Waisfisz, Quinten, Wijnen, Juul, Roozendaal, Cornelis EP van, HEBON, EMBRACE, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare, Frost, Debra, Harrington, Patricia, Evans, D Gareth, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Eccles, Diana, Douglas, Fiona, Brewer, Carole, Nevanlinna, Heli, Heikkinen, Tuomas, Couch, Fergus J, Lindor, Noralane M, Wang, Xianshu, Godwin, Andrew K, Caligo, Maria A, Lombardi, Grazia, Loman, Niklas, Karlsson, Per, Ehrencrona, Hans, Wachenfeldt, Anna von, SWE-BRCA, Barkardottir, Rosa Bjork, Hamann, Ute, Rashid, Muhammad U, Lasa, Adriana, Caldés, Trinidad, Andrés, Raquel, Schmitt, Michael, Assmann, Volker, Stevens, Kristen, Offit, Kenneth, Curado, João, Tilgner, Hagen, Guigó, Roderic, Aiza, Gemma, Brunet, Joan, Castellsagué, Joan, and Martrat, Griselda

Subjects
HEBON, EMBRACE, SWE-BRCA, BCFR, GEMO Study Collaborators, kConFab, Breast, Cell Line, Tumor, Hela Cells, Microtubules, Epithelial Cells, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Protein-Serine-Threonine Kinases, BRCA1 Protein, BRCA2 Protein, Receptors, Estrogen, Extracellular Matrix Proteins, Cell Polarity, Genotype, Heterozygote, Genes, BRCA1, Genes, BRCA2, Female, Genetic Variation, Aurora Kinase A, Aurora Kinases, Hyaluronan Receptors, HeLa Cells, Cell Line, Tumor, Receptors, Estrogen, Genes, BRCA1, BRCA2, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.

Published
2011

17. Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)

Author

Garcia-Tejedor, Amparo, primary, Ortega-Exposito, Carlos, additional, Salinas, Sira, additional, Luzardo-González, Ana, additional, Falo, Catalina, additional, Martinez-Pérez, Evelyn, additional, Pérez-Montero, Héctor, additional, Soler-Monsó, M. Teresa, additional, Bajen, Maria-Teresa, additional, Benitez, Ana, additional, Ortega, Raul, additional, Petit, Anna, additional, Guma, Anna, additional, Campos, Miriam, additional, Plà, Maria J., additional, Pernas, Sonia, additional, Peñafiel, Judith, additional, Yeste, Carlos, additional, Gil-Gil, Miguel, additional, Guedea, Ferran, additional, Ponce, Jordi, additional, and Laplana, Maria, additional

Published
2023
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20. Thyroid cells from normal and autoimmune thyroid glands suppress T lymphocytes proliferation upon contact revealing a new regulatory inhibitory type of interaction independent of PD1/PDL1

Author

Álvarez-Sierra, Daniel, primary, Sánchez-Gaona, Nerea, additional, Cruz Cobo, María, additional, Escriche, Alba, additional, Abad, María, additional, Gómez-Brey, Aroa, additional, Bello, Irene, additional, Caubet, Enric, additional, González, Óscar, additional, Zafón, Carles, additional, Iglesias, Carmela, additional, Moreno, Pablo, additional, Petit, Anna, additional, Fernández-Sanmartín, Marco Antonio, additional, Martínez-Gallo, Mónica, additional, and Pujol-Borrell, Ricardo, additional

Published
2023
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21. Supplementary Figure S1 from Chromosome 12p Amplification in Triple-Negative/BRCA1-Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity

Author

Gómez-Miragaya, Jorge, primary, Díaz-Navarro, Ander, primary, Tonda, Raul, primary, Beltran, Sergi, primary, Palomero, Luis, primary, Palafox, Marta, primary, Dobrolecki, Lacey E., primary, Huang, Chen, primary, Vasaikar, Suhas, primary, Zhang, Bing, primary, Wulf, Gerburg M., primary, Collado-Sole, Alejandro, primary, Trinidad, Eva M., primary, Muñoz, Purificación, primary, Paré, Laia, primary, Prat, Aleix, primary, Bruna, Alejandra, primary, Caldas, Carlos, primary, Arribas, Joaquín, primary, Soler-Monso, María Teresa, primary, Petit, Anna, primary, Balmaña, Judith, primary, Cruz, Cristina, primary, Serra, Violeta, primary, Pujana, Miguel Angel, primary, Lewis, Michael T., primary, Puente, Xose S., primary, and González-Suárez, Eva, primary

Published
2023
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22. RANK is a poor prognosis marker and a therapeutic target in ER‐negative postmenopausal breast cancer

Author

Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Susan G. Komen Foundation, Generalitat de Catalunya, European Research Council, Amgen, Ministerio de Sanidad y Consumo (España), National Institutes of Health (US), Cancer Prevention and Research Institute of Texas, Ciscar, Marina, Trinidad, Eva M., Pérez-Chacón, Gema, Alsaleem, Mansour, Jiménez, María, Jiménez-Santos, María J., Pérez-Montoyo, Héctor, Sanz-Moreno, Adrián, Vethencourt, Andrea, Toss, Michael, Petit, Anna, Soler-Monso, María T., López, Victor, Gómez-Miragaya, Jorge, Gómez-Aleza, Clara, Dobrolecki, Lacey E., Lewis, Michael T., Bruna, Alejandra, Mouron, Silvana, Quintela-Fandino, Miguel, Al-Shahrour, Fátima, Martínez-Aranda, Antonio, Sierra, Angels, Green, Andrew R., Rakha, Emad, González-Suarez, Eva, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Susan G. Komen Foundation, Generalitat de Catalunya, European Research Council, Amgen, Ministerio de Sanidad y Consumo (España), National Institutes of Health (US), Cancer Prevention and Research Institute of Texas, Ciscar, Marina, Trinidad, Eva M., Pérez-Chacón, Gema, Alsaleem, Mansour, Jiménez, María, Jiménez-Santos, María J., Pérez-Montoyo, Héctor, Sanz-Moreno, Adrián, Vethencourt, Andrea, Toss, Michael, Petit, Anna, Soler-Monso, María T., López, Victor, Gómez-Miragaya, Jorge, Gómez-Aleza, Clara, Dobrolecki, Lacey E., Lewis, Michael T., Bruna, Alejandra, Mouron, Silvana, Quintela-Fandino, Miguel, Al-Shahrour, Fátima, Martínez-Aranda, Antonio, Sierra, Angels, Green, Andrew R., Rakha, Emad, and González-Suarez, Eva

Abstract

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor‐negative, ER−) from four independent cohorts. RANK protein expression was more frequent in ER− tumors, where it associated with poor outcome and poor response to chemotherapy. In ER− breast cancer patient‐derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor RANK protein expression associated with poor prognosis in postmenopausal breast cancer patients, activation of NFKB signaling, and modulation of immune and metabolic pathways, suggesting that RANK signaling increases after menopause. Our results demonstrate that RANK protein expression is an independent biomarker of poor prognosis in postmenopausal and ER− breast cancer patients and support the therapeutic benefit of RANK pathway inhibitors, such as denosumab, in breast cancer patients with RANK+ ER− tumors after menopause.

Published
2023

23. Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/ HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact.

Author

Garcia-Tejedor, Amparo, primary, Fernandez-Gonzalez, Sergi, additional, Laplana, Maria, additional, Gil-Gil, Miguel, additional, Martinez, Evelyn, additional, Calvo, Iris, additional, Calpelo, Hugo, additional, Ortega, Raul, additional, Petit, Anna, additional, Guma, Anna, additional, Campos, Miriam, additional, Stradella, Agostina, additional, and López-Ojeda, Ana, additional

Published
2023
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24. Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response

Author

Lejeune, Marylène, primary, Reverté, Laia, additional, Sauras, Esther, additional, Gallardo, Noèlia, additional, Bosch, Ramon, additional, Roso, Albert, additional, Petit, Anna, additional, Peg, Vicente, additional, Riu, Francisco, additional, García-Fontgivell, Joan, additional, Ibáñez, José, additional, Relea, Fernanda, additional, Vieites, Begoña, additional, Bor, Catherine, additional, de la Cruz-Merino, Luis, additional, Arenas, Meritxell, additional, Rodriguez, Valerie, additional, Galera, Juana, additional, Korzynska, Anna, additional, Belhomme, Philippe, additional, Plancoulaine, Benoît, additional, Álvaro, Tomás, additional, and López, Carlos, additional

Published
2023
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25. Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

Author

Lejeune, Marylène, Reverté, Laia, Gallardo, Noèlia, Sauras, Esther, Bosch, Ramon, Mata, Daniel, Roso, Albert, Petit, Anna, Peg, Vicente, Riu, Francisco, García-Fontgivell, Joan, Relea, Fernanda, Vieites, Begoña, de la Cruz-Merino, Luis, Arenas, Meritxell, Rodriguez, Valeri, Galera, Juana, Korzynska, Anna, Plancoulaine, Benoît, and Álvaro, Tomás

Subjects
TRIPLE-negative breast cancer, NEOADJUVANT chemotherapy, CANCER patients, PROGNOSIS, REGULATORY T cells, BREAST
Abstract

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Correction: Author Correction: Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis

Author

Zhang, Xiaowen, Chiang, Huai-Chin, Wang, Yao, Zhang, Chi, Smith, Sabrina, Zhao, Xiayan, Nair, Sreejith J., Michalek, Joel, Jatoi, Ismail, Lautner, Meeghan, Oliver, Boyce, Wang, Howard, Petit, Anna, Soler, Teresa, Brunet, Joan, Mateo, Francesca, Angel Pujana, Miguel, Poggi, Elizabeth, Chaldekas, Krysta, Isaacs, Claudine, Peshkin, Beth N., Ochoa, Oscar, Chedin, Frederic, Theoharis, Constantine, Sun, Lu-Zhe, Curiel, Tyler J., Elledge, Richard, Jin, Victor X., Hu, Yanfen, and Li, Rong

Published
2018
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27. Study of breast cancer incidence in patients of lymphangioleiomyomatosis

Author

Nuñez, Olivier, Román, Antonio, Johnson, Simon R., Inoue, Yoshikazu, Hirose, Masaki, Casanova, Álvaro, de Garibay, Gorka Ruiz, Herranz, Carmen, Bueno-Moreno, Gema, Boni, Jacopo, Mateo, Francesca, Petit, Anna, Climent, Fina, Soler, Teresa, Vidal, August, Sánchez-Mut, José Vicente, Esteller, Manel, López, José Ignacio, García, Nadia, Gumà, Anna, Ortega, Raúl, Plà, María Jesús, Campos, Miriam, Ansótegui, Emilio, Molina-Molina, María, Valenzuela, Claudia, Ussetti, Piedad, Laporta, Rosalía, Ancochea, Julio, Xaubet, Antoni, Pollán, Marina, and Pujana, Miguel Angel

Published
2016
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28. Lymphocytic Thyroiditis Transcriptomic Profiles Support the Role of Checkpoint Pathways and B Cells in Pathogenesis

Author

Álvarez-Sierra, Daniel, primary, Marín-Sánchez, Ana, additional, Gómez-Brey, Aroa, additional, Bello, Irene, additional, Caubet, Enric, additional, Moreno-Llorente, Pablo, additional, Petit, Anna, additional, Zafón, Carles, additional, Iglesias, Carmela, additional, González, Óscar, additional, and Pujol-Borrell, Ricardo, additional

Published
2022
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29. Abstract P2-08-10: First results of the randomized window of opportunity clinical trial D-Biomark: Immunomodulatory effect of denosumab in early breast cancer

Author

Vethencourt, Andrea, primary, Trinidad, Eva M, additional, Petit, Anna, additional, Soler-Monsó, María T, additional, Aleza, Clara Gómez, additional, Urruticochea, Ander, additional, García-Tejedor, Amparo, additional, Martinez, Anna Gumà, additional, Obadia, Veronica, additional, Vazquez, Silvia, additional, Villanueva, Rafael, additional, Fernánez, Adela, additional, Cejuela, Monica, additional, Penabad, Sabela Recalde, additional, Stradella, Agostina, additional, Gil-Gil, Miguel, additional, Pernas, Sonia, additional, Gonzalez-Suarez, Eva, additional, and Falo, Catalina, additional

Published
2022
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30. Abstract P5-07-06: Genomic characterization and tumor evolution in matched(primary-relapse)samplesof patients with METAPLASTIC breast cancer

Author

Cejuela, Mónica, primary, Stradella, Agostina, additional, Petit, Anna, additional, Gargallo, Pablo, additional, Bosch, Jan, additional, Carbonell, Paula, additional, Recalde, Sabela, additional, Vethencourt, Andrea, additional, Fernández, Adela, additional, Falo, Catalina, additional, Gil-Gil, Miguel, additional, Vazquez, Silvia, additional, Villanueva, Rafael, additional, Soler, Teresa, additional, Calabria, Inés, additional, and Pernas, Sonia, additional

Published
2022
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31. RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and a therapeutic target in patient-derived xenografts

Author

Ciscar, Marina, primary, Trinidad, Eva M, additional, Perez-Montoyo, Hector, additional, Alsaleem, Mansour, additional, Jimenez-Santos, Maria J, additional, Toss, Michael, additional, Sanz-Moreno, Adrian, additional, Vethencourt, Andrea, additional, Perez-Chacon, Gema, additional, Petit, Anna, additional, Soler-Monso, Maria T, additional, Gomez-Miragaya, Jorge, additional, Gomez-Aleza, Clara, additional, Jimenez, Maria, additional, Dobrolecki, Lacey E, additional, Lewis, Michael T, additional, Bruna, Alejandra, additional, Mouron, Silvana, additional, Quintela-Fandino, Miguel, additional, Alshahrour, Fatima, additional, Martinez-Aranda, Antonio, additional, Sierra, Angels, additional, Green, Andrew R, additional, Rakha, Emad, additional, and Gonzalez-Suarez, Eva, additional

Published
2021
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33. RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Alsaleem, Mansour, Rakha, Emad A., Green, Andrew R., Santamaria, Patricia G., Mulder, Celine, Lemeer, Simone, Arribas, Joaquin, Prat, Aleix, Puig, Teresa, and Gonzalez-Suarez, Eva

Subjects
Cancer Research, Oncology, skin and connective tissue diseases, neoplasms
Abstract

BackgroundAround 15–20% of primary breast cancers are characterized by HER2 protein overexpression and/or HER2 gene amplification. Despite the successful development of anti-HER2 drugs, intrinsic and acquired resistance represents a major hurdle. This study was performed to analyze the RANK pathway contribution in HER2-positive breast cancer and anti-HER2 therapy resistance.MethodsRANK and RANKL protein expression was assessed in samples from HER2-positive breast cancer patients resistant to anti-HER2 therapy and treatment-naive patients. RANK and RANKL gene expression was analyzed in paired samples from patients treated with neoadjuvant dual HER2-blockade (lapatinib and trastuzumab) from the SOLTI-1114 PAMELA trial. Additionally, HER2-positive breast cancer cell lines were used to modulate RANK expression and analyze in vitro the contribution of RANK signaling to anti-HER2 resistance and downstream signaling.ResultsRANK and RANKL proteins are more frequently detected in HER2-positive tumors that have acquired resistance to anti-HER2 therapies than in treatment-naive ones. RANK (but not RANKL) gene expression increased after dual anti-HER2 neoadjuvant therapy in the cohort from the SOLTI-1114 PAMELA trial. Results in HER2-positive breast cancer cell lines recapitulate the clinical observations, with increased RANK expression observed after short-term treatment with the HER2 inhibitor lapatinib or dual anti-HER2 therapy and in lapatinib-resistant cells. After RANKL stimulation, lapatinib-resistant cells show increased NF-κB activation compared to their sensitive counterparts, confirming the enhanced functionality of the RANK pathway in anti-HER2-resistant breast cancer. Overactivation of the RANK signaling pathway enhances ERK and NF-κB signaling and increases lapatinib resistance in different HER2-positive breast cancer cell lines, whereas RANK loss sensitizes lapatinib-resistant cells to the drug. Our results indicate that ErbB signaling is required for RANK/RANKL-driven activation of ERK in several HER2-positive cell lines. In contrast, lapatinib is not able to counteract the NF-κB activation elicited after RANKL treatment in RANK-overexpressing cells. Finally, we show that RANK binds to HER2 in breast cancer cells and that enhanced RANK pathway activation alters HER2 phosphorylation status.ConclusionsOur data support a physical and functional link between RANK and HER2 signaling in breast cancer and demonstrate that increased RANK signaling may contribute to the development of lapatinib resistance through NF-κB activation. Whether HER2-positive breast cancer patients with tumoral RANK expression might benefit from dual HER2 and RANK inhibition therapy remains to be elucidated.

Published
2021

35. Assessment of Tumor Cell Death After Percutaneous Ultrasound– Guided Radiofrequency Ablation of Breast Carcinoma: A Prospective Study

Author

Guma, Anna, primary, Soler, Teresa, additional, Chappuis, César G., additional, Valdivielso, Alazne, additional, Petit, Anna, additional, Pla, Maria J., additional, Falo, Catalina, additional, Pernas, Sònia, additional, Ortega, Raúl, additional, Vicente, María, additional, Pérez, Laia, additional, Fernandez-Montoli, Eulalia, additional, Campos, Miriam, additional, Burdio, Fernando, additional, Ponce, Jordi, additional, Calvo, Nahum, additional, and Garcia-Tejedor, Amparo, additional

Published
2021
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36. Additional file 6 of RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A., Green, Andrew R., Santamaria, Patricia G., Celine Mulder, Lemeer, Simone, Joaquin Arribas, Aleix Prat, Puig, Teresa, and Gonzalez-Suarez, Eva

Subjects
skin and connective tissue diseases
Abstract

Additional file 6: Figure S6. A. Relative number of living (relative survival) SKBR3 RANK cells stimulated with RANKL in the presence or absence of denosumab (DNS) and incubated for 4 days with the indicated concentrations of lapatinib. Cells were seeded in growth media with/without denosumab (1 μg/ml), lapatinib was added after 24 h stimulation with 100 ng/ml RANKL, and cell viability was analyzed with CCK8 as detailed in methods. Determinations were done in triplicates, mean values from n ≥ 2 independent experiments and SD are depicted. B. Western blot analyses of total levels of p65, ERK1/2 and HER2 in whole lysates from SKBR3, BT474 and HCC1954 cells stably transduced with control (empty) or RANK overexpressing (RANK) vectors as depicted in Fig. 5d. Before collecting the cells, they were cultured in media without FBS for 12 h, pretreated with/without lapatinib for 2 h followed by 10 min stimulation with RANKL. Tubulin was used as a loading control. C. Table depicting the relative phospho-protein levels of the indicated proteins from the western blots shown in Fig. 5d and Fig. S6B determined by densitometry analyses with Image J.

Published
2021
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37. Additional file 3 of RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A., Green, Andrew R., Santamaria, Patricia G., Celine Mulder, Lemeer, Simone, Joaquin Arribas, Aleix Prat, Puig, Teresa, and Gonzalez-Suarez, Eva

Abstract

Additional file 3: Figure S3. RANK and RANKL expression in breast cancer samples from the PAMELA clinical trial. A. Expression of RANK and RANKL across the intrinsic molecular subtypes from the PAMELA study. P values were calculated by comparing mean values across all groups. B. Scatter plots of RANK and RANKL expression versus ERBB2 expression for baseline samples in the PAMELA study. Solid line in each figure represents the regression line. Pearson correlation coefficient (r) with significance (p value) is presented in each figure. C. Pearson correlation between single genes and gene expression signatures evaluated in baseline samples from the PAMELA study.

Published
2021
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38. Additional file 5 of RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A., Green, Andrew R., Santamaria, Patricia G., Celine Mulder, Lemeer, Simone, Joaquin Arribas, Aleix Prat, Puig, Teresa, and Gonzalez-Suarez, Eva

Subjects
musculoskeletal diseases, skin and connective tissue diseases
Abstract

Additional file 5: Figure S5. A. Relative number of living (relative survival) SKBR3 and SKLR control cells incubated for 4 days with the indicated concentrations of lapatinib and stimulated with RANKL. Cells were seeded in growth media, 100 ng/ml RANKL were added 24h after seeding, lapatinib was added 24 h later and cells were analyzed with CCK8 as detailed in methods. Determinations were done in triplicates, mean values are depicted from n = 5 independent experiments and SD and p-value (**) calculated by one-way ANOVA is depicted (p ≤ 0.05 for SKBR3 vs SKLR and SKLR +RANKL, SKBR3 +RANKL vs SKLR and SKLR +RANKL; n.s. for SKBR3 vs SKBR3 +RANKL and SKLR vs SKLR +RANKL). Significance of relative survival was calculated for each concentration using two-tailed p values for one sample t test. RANKL significantly increased survival of SKLR cells at 0.018 μM of lapatinib (p = 0.019). B. Western blot showing the total levels of IκB, p65, ERK1/2, AKT and HER2 in SKBR3 control, SKLR control and SKLR sh#3 cells treated with RANKL or lapatinib as depicted in Fig. 4c. Cells were serum starved for 12 h and then treated with lapatinib (2 h) or RANKL (10 min) before processing them. Tubulin was used as a loading control. C. Table depicting the relative phospho-protein levels of the indicated proteins from the western blots shown in Fig. 4c and Fig. S5B determined by densitometry analyses with Image J.

Published
2021
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39. Additional file 7 of RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A., Green, Andrew R., Santamaria, Patricia G., Celine Mulder, Lemeer, Simone, Joaquin Arribas, Aleix Prat, Puig, Teresa, and Gonzalez-Suarez, Eva

Subjects
skin and connective tissue diseases
Abstract

Additional file 7: Figure S7. Western blot analyses of HER2 (p-HER2, p-ERK1/2) and NF-κB (p-p65) pathway activation in SKBR3, BT474 and HCC1954 cells stably transduced with empty or RANK overexpressing (RANK) vectors. Cells were cultured in media without FBS for 12 h, followed by stimulation with EGF (100 ng/ml) (upper panels) or heregulin (HRG 10 ng/ml) (lower panels) for the indicated times. Tubulin was used as a loading control.

Published
2021
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40. RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Author

Sub Biomol.Mass Spectrometry & Proteom., Sub Education Institute Chemistry, Biomolecular Mass Spectrometry and Proteomics, Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A, Green, Andrew R, Santamaria, Patricia G, Mulder, Celine, Lemeer, Simone, Arribas, Joaquin, Prat, Aleix, Puig, Teresa, Gonzalez-Suarez, Eva, Sub Biomol.Mass Spectrometry & Proteom., Sub Education Institute Chemistry, Biomolecular Mass Spectrometry and Proteomics, Sanz-Moreno, Adrián, Palomeras, Sonia, Pedersen, Kim, Morancho, Beatriz, Pascual, Tomas, Galván, Patricia, Benítez, Sandra, Gomez-Miragaya, Jorge, Ciscar, Marina, Jimenez, Maria, Pernas, Sonia, Petit, Anna, Soler-Monsó, María Teresa, Viñas, Gemma, Alsaleem, Mansour, Rakha, Emad A, Green, Andrew R, Santamaria, Patricia G, Mulder, Celine, Lemeer, Simone, Arribas, Joaquin, Prat, Aleix, Puig, Teresa, and Gonzalez-Suarez, Eva

Published
2021

41. RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and a therapeutic target in patient-derived xenografts

Author

Ciscar, Marina, Trinidad, Eva M., Pérez-Montoyo, Héctor, Alsaleem, Mansour, Jiménez-Santos, María J., Toss, Michael, Sanz-Moreno, Adrián, Vethencourt, Andrea, Pérez-Chacón, Gema, Petit, Anna, Soler-Monso, María T., Gómez-Miragaya, Jorge, Gómez-Aleza, Clara, Jiménez, María, Dobrolecki, Lacey E., Lewis, Michael T., Bruna, Alejandra, Mouron, Silvana, Quintela-Fandino, Miguel, Al-Shahrour, Fátima, Martínez-Aranda, Antonio, Sierra, Angels, Green, Andrew R., Rakha, Emad, González-Suarez, Eva, Ciscar, Marina, Trinidad, Eva M., Pérez-Montoyo, Héctor, Alsaleem, Mansour, Jiménez-Santos, María J., Toss, Michael, Sanz-Moreno, Adrián, Vethencourt, Andrea, Pérez-Chacón, Gema, Petit, Anna, Soler-Monso, María T., Gómez-Miragaya, Jorge, Gómez-Aleza, Clara, Jiménez, María, Dobrolecki, Lacey E., Lewis, Michael T., Bruna, Alejandra, Mouron, Silvana, Quintela-Fandino, Miguel, Al-Shahrour, Fátima, Martínez-Aranda, Antonio, Sierra, Angels, Green, Andrew R., Rakha, Emad, and González-Suarez, Eva

Abstract

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor denosumab in BC patients, beyond its bone-related effects, is unclear. Here, we investigated the prognostic value of RANK expression and its functionality in human BC. We analyzed RANK and RANKL expression in more than 1500 BC cases (777 being estrogen receptor-negative (ER-)) from four independent cohorts. We confirmed that RANK is more frequently expressed in ER- tumors, but it is also found in a subset of ER+ tumors. In ER- BC, RANK expression was independently associated with poor outcome, especially in postmenopausal patients and those who received adjuvant chemotherapy. Gene expression analyses unraveled distinct biology associated with RANK in relation to ER expression and menopause, and evidenced enhanced RANK activation in ER- postmenopausal tumors, together with regulation of metabolic pathways. Functional studies and transcriptomic analyses in ER- RANK+ patients-derived orthoxenografts demonstrated that activation of RANK signaling pathway promotes tumor cell proliferation and stemness, and regulates multiple biological processes including tumor immune surveillance and metabolism. Our results demonstrate that RANK expression is an independent poor prognosis biomarker in postmenopausal ER- BC patients and support the rational of using RANK pathway inhibitors in combination with chemotherapy in ER- BC.

Published
2021

42. Efficacy and safety of concurrent trastuzumab plus weekly paclitaxel–FEC as primary therapy for HER2-positive breast cancer in everyday clinical practice

Author

Pernas, Sonia, Gil-Gil, Miguel, de Olza, María Ochoa, Gumà, Anna, Climent, Fina, Petit, Anna, Pla, María Jesús, García-Tejedor, Amparo, López-Ojeda, Ana, Falo, Cati, Fernandez-Otega, Adela, Mesia, Carlos, Pérez-Martin, Francisco Javier, Urruticoechea, Ander, and Germà, Josep Ramon

Published
2012
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43. Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

Author

Garcia-Tejedor, Amparo, primary, Fernandez-Gonzalez, Sergi, additional, Ortega, Raul, additional, Gil-Gil, Miguel, additional, Perez-Montero, Hector, additional, Fernandez-Montolí, Eulalia, additional, Stradella, Agostina, additional, Recalde, Sabela, additional, Soler, Teresa, additional, Petit, Anna, additional, Bajen, Maria Teresa, additional, Benitez, Ana, additional, Guma, Anna, additional, Campos, Miriam, additional, Pla, Maria J., additional, Martinez, Evelyn, additional, Laplana, Maria, additional, Pernas, Sonia, additional, Perez-Sildekova, Diana, additional, Catala, Isabel, additional, Ponce, Jordi, additional, and Falo, Catalina, additional

Published
2020
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48. Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance

Author

Ruiz de Garibay, Gorka, Mateo, Francesca, Stradella, Agostina, Valdés-Mas, Rafael, Palomero, Luis, Serra-Musach, Jordi, Puente, Diana A., Díaz-Navarro, Ander, Vargas-Parra, Gardenia, Tornero, Eva, Morilla, Idoia, Farré, Lourdes, Martinez-Iniesta, María, Herranz, Carmen, McCormack, Emmet, Vidal, August, Petit, Anna, Soler, Teresa, Lázaro, Conxi, Puente, Xose S., Villanueva, Alberto, Pujana, Miguel Angel, and Universitat de Barcelona

Subjects
Adult, Medical screening, Resistance, lcsh:Medicine, Breast Neoplasms, Càncer de mama, Quimioteràpia del càncer, Genetic Heterogeneity, Mice, Breast cancer, Transcription Factor 4, Patient-derived xenograft, Cell Line, Tumor, lcsh:Pathology, Transcription factors, Chemotherapy, Animals, Humans, Resistència als medicaments, TCF4, Base Sequence, Xenograft, lcsh:R, Cell Cycle, Prognosis, Adaptation, Physiological, Xenograft Model Antitumor Assays, Cribratge, Drug Resistance, Neoplasm, Factors de transcripció, Drug resistance, Mutation, Female, Cancer chemotherapy, Transcription factor, lcsh:RB1-214, Research Article
Abstract

Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2) is associated with this process. A triple-negative BRCA1-mutated PDX was used to study the genetics of chemoresistance. The PDX was treated in parallel with four chemotherapies for five iterative cycles. Exome sequencing identified few genes with de novo or enriched mutations in common among the different therapies, whereas many common depleted mutations/genes were observed. Analysis of somatic mutations from The Cancer Genome Atlas (TCGA) supported the prognostic relevance of the identified genes. A mutation in TCF4 was found de novo in all treatments, and analysis of drug sensitivity profiles across cancer cell lines supported the link to chemoresistance. Loss of TCF4 conferred chemoresistance in breast cancer cell models, possibly by altering cell cycle regulation. Targeted sequencing in chemoresistant tumors identified an intronic variant of TCF4 that may represent an expression quantitative trait locus associated with relapse outcome in TCGA. Immunohistochemical studies suggest a common loss of nuclear TCF4 expression post-chemotherapy. Together, these results from tumor xenograft modeling depict a link between altered TCF4 expression and breast cancer chemoresistance., Summary: By modeling chemoresistance in patient-derived breast cancer xenografts, this study shows that adaptation to therapy is genetically complex and that loss of transcription factor 4 (TCF4) is associated with this process.

Published
2018

49. Corrigendum: PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution

Author

Pernas, Sonia, primary, Petit, Anna, additional, Climent, Fina, additional, Paré, Laia, additional, Perez-Martin, J., additional, Ventura, Luz, additional, Bergamino, Milana, additional, Galván, Patricia, additional, Falo, Catalina, additional, Morilla, Idoia, additional, Fernandez-Ortega, Adela, additional, Stradella, Agostina, additional, Rey, Montse, additional, Garcia-Tejedor, Amparo, additional, Gil-Gil, Miguel, additional, and Prat, Aleix, additional

Published
2019
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50. Chromosome 12p Amplification in Triple-Negative/BRCA1-Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity

Author

Gómez-Miragaya, Jorge, primary, Díaz-Navarro, Ander, additional, Tonda, Raul, additional, Beltran, Sergi, additional, Palomero, Luis, additional, Palafox, Marta, additional, Dobrolecki, Lacey E., additional, Huang, Chen, additional, Vasaikar, Suhas, additional, Zhang, Bing, additional, Wulf, Gerburg M., additional, Collado-Sole, Alejandro, additional, Trinidad, Eva M., additional, Muñoz, Purificación, additional, Paré, Laia, additional, Prat, Aleix, additional, Bruna, Alejandra, additional, Caldas, Carlos, additional, Arribas, Joaquín, additional, Soler-Monso, María Teresa, additional, Petit, Anna, additional, Balmaña, Judith, additional, Cruz, Cristina, additional, Serra, Violeta, additional, Pujana, Miguel Angel, additional, Lewis, Michael T., additional, Puente, Xose S., additional, and González-Suárez, Eva, additional

Published
2019
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