Molecular Characterization of Basal-Like and Non-Basal-Like Triple-Negative Breast Cancer
TLDR
The results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.Abstract:
Triple-negative (TN) and basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormone receptors and overexpression and/or amplification of HER2. However, both classifications show substantial discordance rates when compared to each other. Here, we molecularly characterize TN tumors and BL tumors, comparing and contrasting the results in terms of common patterns and distinct patterns for each. In total, when testing 412 TN and 473 BL tumors, 21.4% and 31.5% were identified as non-BL and non-TN, respectively. TN tumors identified as luminal or HER2-enriched (HER2E) showed undistinguishable overall gene expression profiles when compared versus luminal or HER2E tumors that were not TN. Similar findings were observed within BL tumors regardless of their TN status, which suggests that molecular subtype is preserved regardless of individual marker results. Interestingly, most TN tumors identified as HER2E showed low HER2 expression and lacked HER2 amplification, despite the similar overall gene expression profiles to HER2E tumors that were clinically HER2-positive. Lastly, additional genomic classifications were examined within TN and BL cancers, most of which were highly concordant with tumor intrinsic subtype. These results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.read more
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Journal ArticleDOI
BRCA Mutational Status is a Promising Predictive Biomarker for Platinum- based Chemotherapy in Triple-Negative Breast Cancer.
TL;DR: In this paper, the potential of BRCA mutational status as a predictive biomarker of platinum-based chemotherapy in triple negative breast cancer (TNBC) patients was discussed.
Book ChapterDOI
Triple-Negative Breast Cancer: Expression of Hypoxia-Inducible Factor 1α in Triple-Negative Breast Cancer with Metastasis to Lymph Nodes
TL;DR: TNBC subgroup demonstrated significant correlation between HIF-1α expression and tumor size (pT1–pT4) (p = 0.021), which may suggest that Hif-1 alpha expression in this group of patients may be an additional and significant marker in the evaluation of the advance of the disease, affecting therapeutic decisions.
Dissertation
Identification of mechanisms of acquired resistance to taxanes in triple negative breast cancer using patient-derived xenografts: a step closer to clinics
TL;DR: The findings suggest that there is a subset of TNBC/basal-like breast cancer harbouring chr12p amplification that may be associated with resistance to docetaxel treatment in clinical setting, and a set of promising pathways that may contribute to the acquisition of chemoresistance in TNBC patients are identified.
Journal ArticleDOI
The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer.
Xin Tian,Xin Tian,Hua Yu,Hua Yu,Dong Li,Guojiang Jin,Shundong Dai,Pengchao Gong,Cuicui Kong,Xiongjun Wang,Xiongjun Wang +10 more
TL;DR: It is found that depletion of AF9 significantly promoted MCF-7 cell invasion and migration and restoring expression of the metastasis suppressor AF9 is a possible therapeutic strategy against metastatic breast cancer.
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Molecular portraits of human breast tumours
Charles M. Perou,Therese Sørlie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,Christian A. Rees,Jonathan R. Pollack,Douglas T. Ross,Hilde Johnsen,Lars A. Akslen,Øystein Fluge,Alexander Pergamenschikov,Cheryl A. Williams,Shirley Zhu,Per Eystein Lønning,Anne Lise Børresen-Dale,Patrick O. Brown,David Botstein +17 more
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Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
Therese Sørlie,Charles M. Perou,Robert Tibshirani,Turid Aas,Stephanie Geisler,Hilde Johnsen,Trevor Hastie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,T. Thorsen,Hanne Quist,John C. Matese,Patrick O. Brown,David Botstein,Per Eystein Lønning,Anne Lise Børresen-Dale +16 more
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Comprehensive molecular portraits of human breast tumours
Daniel C. Koboldt,Robert S. Fulton,Michael D. McLellan,Heather Schmidt,Joelle Kalicki-Veizer,Joshua F. McMichael,Lucinda Fulton,David J. Dooling,Li Ding,Elaine R. Mardis,Richard K. Wilson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Rebecca Carlsen,Candace Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Jacqueline E. Schein,Arash Shafiei,Payal Sipahimalani,Jared R. Slobodan,Dominik Stoll,Angela Tam,Nina Thiessen,Richard Varhol,Natasja Wye,Thomas Zeng,Yongjun Zhao,Inanc Birol,Steven J.M. Jones,Marco A. Marra,Andrew D. Cherniack,Gordon Saksena,Gordon Saksena,Robert C. Onofrio,Nam H. Pho,Scott L. Carter,Steven E. Schumacher,Steven E. Schumacher,Barbara Tabak,Barbara Tabak,Bryan Hernandez,Jeff Gentry,Huy Nguyen,Andrew Crenshaw,Kristin G. 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Teresiak,Honorata Tatka,Ewa Leporowska,Marta Bogusz-Czerniewicz,Julian Malicki,Andrzej Mackiewicz,Maciej Wiznerowicz,Xuan Van Le,Bernard Kohl,Nguyen Viet Tien,Richard Thorp,Nguyen Van Bang,Howard H. Sussman,Bui Duc Phu,Richard A. Hajek,Nguyen Phi Hung,Huynh Quyet Thang,Khurram Z. Khan,Robert Penny,David Mallery,Erin Curley,Candace Shelton,Peggy Yena,James N. Ingle,Fergus J. Couch,Wilma L. Lingle,Tari A. King,Ana M. Gonzalez-Angulo,Ana M. Gonzalez-Angulo,Mary D. Dyer,Shuying Liu,Xiaolong Meng,Modesto Patangan,Frederic Waldman,Frederic Waldman,Hubert Stoppler,W. Kimryn Rathmell,Leigh B. Thorne,Mei Huang,Lori Boice,Ashley Hill,Carl Morrison,Carmelo Gaudioso,Wiam Bshara,Kelly Daily,Sophie C. Egea,Mark D. Pegram,Carmen Gomez-Fernandez,Rajiv Dhir,Rohit Bhargava,Adam Brufsky,Craig D. Shriver,Jeffrey A. Hooke,Jamie Leigh Campbell,Richard J. Mural,Hai Hu,Stella Somiari,Caroline Larson,Brenda Deyarmin,Leonid Kvecher,Albert J. Kovatich,Matthew J. Ellis,Thomas Stricker,Kevin P. White,Olufunmilayo I. Olopade,Chunqing Luo,Yaqin Chen,Ron Bose,Li-Wei Chang,Andrew H. Beck,Todd Pihl,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Brenda Ayala,Mark Backus,Jessica Walton,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,David Pot,Margi Sheth,John A. Demchok,Kenna R. Mills Shaw,Liming Yang,Greg Eley,Martin L. Ferguson,Roy Tarnuzzer,Jiashan Zhang,Laura A.L. Dillon,Kenneth H. Buetow,Peter Fielding,Bradley A. Ozenberger,Mark S. Guyer,Heidi J. Sofia,Jacqueline D. Palchik +355 more
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
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