Abstract

Triple-negative inflammatory breast cancer (TN-IBC) is the most aggressive type of breast cancer, yet its defining genomic, molecular, and immunological features remain largely unknown. In this study, we performed the largest and most comprehensive genomic and transcriptomic analyses of prospectively collected TN-IBC patient samples from a phase II clinical trial (ClinicalTrials.gov, NCT02876107, registered on August 22, 2016) and compared them to similarly analyzed stage III TN-non-IBC patient samples (ClinicalTrials.gov, NCT02276443, registered on October 21, 2014). We found that TN-IBC tumors have distinctive genomic, molecular, and immunological characteristics, including a lower tumor mutation load than TN-non-IBC, and an association of immunosuppressive tumor-infiltrating immune components with an unfavorable response to neoadjuvant chemotherapy. To our knowledge, this is the only study in which TN-IBC and TN-non-IBC samples were collected prospectively. Our analysis improves the understanding of the molecular landscape of the most aggressive subtype of breast cancer. Further studies are needed to discover novel prognostic biomarkers and druggable targets for TN-IBC.

Details

Title
Genomic and transcriptomic analyses identify distinctive features of triple-negative inflammatory breast cancer
Author
Wang, Xiaoping 1 ; Zhao, Li 2 ; Song, Xingzhi 2 ; Wu, Xiaogang 2 ; Krishnamurthy, Savitri 3 ; Semba, Takashi 4 ; Shao, Shan 4 ; Knafl, Mark 2   VIAFID ORCID Logo  ; Coffer, Larry W. 4 ; Alexander, Angela 4   VIAFID ORCID Logo  ; Vines, Anita 4 ; Bopparaju, Swetha 4 ; Woodward, Wendy A. 5 ; Chu, Randy 2 ; Zhang, Jianhua 2 ; Yam, Clinton 6 ; Loo, Lenora W. M. 7 ; Nasrazadani, Azadeh 4 ; Huong, Le-Petross 8 ; Woodman, Scott E. 2 ; Futreal, Andrew 2   VIAFID ORCID Logo  ; Rawi, Ahmed N. Al 2 ; Arrechedera, Claudio A. 2 ; Ayers, Kimberly S. 2 ; Bedoya, Claudia Alvarez 2 ; Burton, Elizabeth 2 ; Chon, Connie A. 2 ; Chu, Randy Aaron 2 ; Crosby, Shadarra D. 2 ; Do, Jonathan 2 ; Lima, Cibelle Freitas Pinto 2 ; Fu, Szu-Chin 2 ; Futreal, Andy 2 ; Garcia, Ana L. 2 ; Garcia-Prieto, Celia 2 ; Gite, Swati 2 ; Gumbs, Curtis 2 ; Hargraves, Kristin J. 2 ; He, Meng 2 ; Horombe, Chacha 2 ; Ibarguen, Heladio P. 2 ; Jackson, Stacy 2 ; Jacob, Jeena 2 ; Jiang, Mei 2 ; Khanduri, Isha 2 ; Kinyua, Walter K. 2 ; Lang, Wenhua 2 ; Little, Latasha D. 2 ; Lu, Wei 2 ; Mallampati, Saradhi 2 ; Mendoza, Mary Gertrude T. 2 ; Meric-Bernstam, Funda 2 ; Mohammad, Mohammad Moustaf 2 ; Piubelli, Mario Luiz Marques 2 ; Prabhakaran, Sabitha 2 ; Shaw, Kenna R. 2 ; Song, Ping 2 ; Song, Xiaofei 2 ; Subramanya, Sandesh 2 ; Sun, Baohua 2 ; Virani, Shumaila 2 ; Wang, Wanlin 2 ; Wistuba, Ignacio 2 ; Xu, Mingchu 2 ; Zhang, Qingxiu C. 2 ; Zhang, Shanyu 2 ; Tripathy, Debu 6   VIAFID ORCID Logo  ; Ueno, Naoto T. 1   VIAFID ORCID Logo 

1  The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); University of Hawai’i Cancer Center, Honolulu, USA (GRID:grid.240145.6) 
2  The University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
3  The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Pathology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
4  The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
5  The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Breast Radiation Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
6  The University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
7  University of Hawai’i Cancer Center, Honolulu, USA (GRID:grid.240145.6) 
8  The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Breast Imaging, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
Pages
265
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
ISSN
2397768X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41698-024-00729-0
ProQuest document ID
3129874959
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.