Genomic and transcriptomic analyses identify distinctive features of triple-negative inflammatory breast cancer

Xiaoping Wang; Li Zhao; Xingzhi Song; Xiaogang Wu; Savitri Krishnamurthy; Takashi Semba; Shan Shao; Mark Knafl; Larry W Coffer 2nd; Angela Alexander; Anita Vines; Swetha Bopparaju; Wendy A Woodward; Randy Chu; Jianhua Zhang; Clinton Yam; Lenora W M Loo; Azadeh Nasrazadani; Le-Petross Huong; Scott E Woodman; Andrew Futreal; Rare Tumor Initiative Team; Debu Tripathy; Naoto T Ueno

doi:10.1038/s41698-024-00729-0

Genomic and transcriptomic analyses identify distinctive features of triple-negative inflammatory breast cancer

NPJ Precis Oncol. 2024 Nov 18;8(1):265. doi: 10.1038/s41698-024-00729-0.

Authors

Xiaoping Wang^#^{1

2

3}, Li Zhao^#⁴, Xingzhi Song⁴, Xiaogang Wu⁴, Savitri Krishnamurthy^{5

6}, Takashi Semba^{5

7}, Shan Shao^{5

7}, Mark Knafl⁴, Larry W Coffer 2nd^{5

7}, Angela Alexander^{5

7}, Anita Vines^{5

7}, Swetha Bopparaju^{5

7}, Wendy A Woodward^{5

8}, Randy Chu⁴, Jianhua Zhang⁴, Clinton Yam⁷, Lenora W M Loo⁹, Azadeh Nasrazadani^{5

7}, Le-Petross Huong^{5

10}, Scott E Woodman⁴, Andrew Futreal⁴; Rare Tumor Initiative Team; Debu Tripathy⁷, Naoto T Ueno^{11

12

13}

Collaborators

Rare Tumor Initiative Team:
Ahmed N Al Rawi, Claudio A Arrechedera, Kimberly S Ayers, Claudia Alvarez Bedoya, Elizabeth Burton, Connie A Chon, Randy Aaron Chu, Shadarra D Crosby, Jonathan Do, Cibelle Freitas Pinto Lima, Szu-Chin Fu, Andy Futreal, Ana L Garcia, Celia Garcia-Prieto, Swati Gite, Curtis Gumbs, Kristin J Hargraves, Meng He, Chacha Horombe, Heladio P Ibarguen, Stacy Jackson, Jeena Jacob, Mei Jiang, Isha Khanduri, Walter K Kinyua, Wenhua Lang, Latasha D Little, Wei Lu, Saradhi Mallampati, Mary Gertrude T Mendoza, Funda Meric-Bernstam, Mohammad Moustaf Mohammad, Mario Luiz Marques Piubelli, Sabitha Prabhakaran, Kenna R Shaw, Ping Song, Xiaofei Song, Sandesh Subramanya, Baohua Sun, Shumaila Virani, Wanlin Wang, Ignacio Wistuba, Mingchu Xu, Qingxiu C Zhang, Shanyu Zhang

Affiliations

¹ Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [email protected].
² Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [email protected].
³ University of Hawai'i Cancer Center, Honolulu, HI, USA. [email protected].
⁴ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ University of Hawai'i Cancer Center, Honolulu, HI, USA.
¹⁰ Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹ Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [email protected].
¹² Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [email protected].
¹³ University of Hawai'i Cancer Center, Honolulu, HI, USA. [email protected].

^# Contributed equally.

PMID: 39558017
DOI: 10.1038/s41698-024-00729-0

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.

Associated data

ClinicalTrials.gov/NCT02876107
ClinicalTrials.gov/NCT02276443