Skip to main content

ORIGINAL RESEARCH article

Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1522262

The evolving landscape of genetic biomarkers for immunotherapy between primary and metastatic breast cancer

Provisionally accepted
Liang Jin Liang Jin 1Zijian Yang Zijian Yang 2Wei Tang Wei Tang 3Pengli Yu Pengli Yu 4Rongrong Chen Rongrong Chen 4Yan Xu Yan Xu 5*Jun Zhang Jun Zhang 6*
  • 1 Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong Province, China
  • 2 Shenzhen Hospital, Peking University, Shenzhen, Beijing Municipality, China
  • 3 First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
  • 4 Geneplus Beijing Institute, Huilongguan Town, China
  • 5 Daping Hospital, Chongqing, China
  • 6 Shenzhen Shekou People’s Hospital, Shenzhen, China

The final, formatted version of the article will be published soon.

    Background: Major advances have been achieved in the characterization of primary breast cancer genomic profiles. Limited information is available on the genomic profile of tumors originated from different metastatic locations in recurrent/metastatic (R/M) breast cancer, especially in Asia patients. This study aims to decipher mutational profiles between primary and R/M breast cancer in Chinese patients using nextgeneration sequencing.Methods: A total of 563 breast cancer patients were enrolled, 590 tumor tissues and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1,021 cancer-related genes. The mutation spectrum, DNA damage response (DDR) genes, commonly altered signal pathways and immunotherapy-related markers were compared between primary and R/M breast cancers. The molecular differences between our cohort and MSKCC were also explored.Results: A total of 361 samples from primary and 229 samples from R/M breast were analyzed. BRCA2, ATRX and ATM were more frequently observed in R/M lesions among 36 DDR genes. ESR1 mutation, PD-L1 and PD-L2 amplification were enriched in R/M breast cancers (all p<0.05). Compared with MSKCC dataset, we recruited more patients diagnosed at age 50 or younger and more patients with TNBC subtypes. Triplenegative breast cancers (TNBC) patients in our dataset had higher percentage of PD-L1 amplification in metastasis tumors (p<0.05).This study revealed the distinctive mutational features between primary and R/M tumors in Chinese breast cancer patients, which is different from the ones in western countries. The enrichment of PD-L1 amplification in metastatic TNBC indicates the necessity to re-biopsy metastatic tumors for immunotherapy.

    Keywords: breast cancer, Genomic profile, Primary tumor, Immunotherapy, PD-L1 amplification, TNBC

    Received: 04 Nov 2024; Accepted: 30 Jan 2025.

    Copyright: © 2025 Jin, Yang, Tang, Yu, Chen, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yan Xu, Daping Hospital, Chongqing, 400042, China
    Jun Zhang, Shenzhen Shekou People’s Hospital, Shenzhen, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.