Genomic and transcriptomic profiling of pre‐ and postneoadjuvant chemotherapy triple negative breast cancer tumors
Our understanding of neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) remains limited. To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Lower PIK3CA, PTEN, and HRAS mutations were found in homologous recombination deficiency (HRD)-high (HRD score ≥ 42) tumors with higher pCR rates. When HRD-high tumors were stratified by tumor BRCA mutation status, the pCR rates in BRCA2-mutated tumors were higher (83% vs. 36%). Transcriptomic profiling of TP53-positive tumors identified downregulation of FGFR2 (false discovery rate p value = 2.07e-7), which was also the only common gene between HRD-high and -low tumors with pCR/quasi-pCR treated with paclitaxel and eribulin combined with carboplatin, respectively. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.
Authors
- Yutaka Yamamoto (ORCID: https://orcid.org/0000-0001-6147-6828)
- Hironori Haga (ORCID: https://orcid.org/0000-0003-4322-9561)
- Kosuke Kawaguchi (ORCID: https://orcid.org/0000-0002-3161-7981)
- Fumihiko Matsuda (ORCID: https://orcid.org/0000-0003-4557-4553)
- Yurina Maeshima
- Masahiro Takada (ORCID: https://orcid.org/0000-0002-5954-1296)
- Hiroko Bando (ORCID: https://orcid.org/0000-0002-7361-3647)
- Shuji Kawaguchi (ORCID: https://orcid.org/0000-0002-4045-6518)
- Shinji Ohno (ORCID: https://orcid.org/0000-0003-2093-3353)
- Takayuki Ueno (ORCID: https://orcid.org/0000-0002-9080-9377)
- Seishi Ogawa (ORCID: https://orcid.org/0000-0002-7778-5374)
- Takayuki Kadoya (ORCID: https://orcid.org/0000-0003-1835-1266)
- Yuichiro Kikawa (ORCID: https://orcid.org/0000-0002-3852-5991)
- Norikazu Masuda (ORCID: https://orcid.org/0000-0002-7302-0278)
- Hiroyuki Yasojima (ORCID: https://orcid.org/0009-0005-3729-1520)
- Ravi Velaga (ORCID: https://orcid.org/0009-0002-5962-0266)
- Rikiya Nakamura (ORCID: https://orcid.org/0000-0002-4349-9046)
- Masakazu Toi (ORCID: https://orcid.org/0000-0003-1488-9958)
- Hiroshi Ishiguro (ORCID: https://orcid.org/0000-0002-0805-7648)
- Sunao Tanaka
- Satoshi Morita (ORCID: https://orcid.org/0000-0002-4344-3317)
- T Nishimura (ORCID: https://orcid.org/0009-0008-1999-5147)
Institutions
- Kansai Medical University (JP)
- University of Tsukuba (JP)
- Kyoto University (JP)
- Karolinska Institutet (SE)
- Tokyo Metropolitan Komagome Hospital (JP)
- Osaka National Hospital (JP)
- Chiba Cancer Center (JP)
- National Sagamihara Hospital (JP)
- Saitama International Medical Center (JP)
- The Cancer Institute Hospital (JP)
- Shimane University Hospital (JP)
- Kyoto University Hospital (JP)
- Kobe City Medical Center General Hospital (JP)
- Nagoya University (JP)
- Saitama Medical University (JP)
- Kumamoto University (JP)
Publication Details
- Journal
- Cancer Science
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1111/cas.16339
- Citations
- 4
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 1.14
Funders
- Eli Lilly and Company
- Pfizer
- Eisai
- Chugai Pharmaceutical
- Daiichi Sankyo Europe