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Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2-negative metastatic breast cancer.
Park, Changhee; Suh, Koung Jin; Kim, Se Hyun; Lee, Kyung-Hun; Im, Seock-Ah; Kim, Min Hwan; Sohn, Joohyuk; Jeong, Jae Ho; Jung, Kyung Hae; Lee, Kyoung Eun; Park, Yeon Hee; Kim, Hee-Jun; Cho, Eun Kyung; Choi, In Sil; Noh, Seung-Jae; Shin, Inkyung; Cho, Dae-Yeon; Kim, Jee Hyun.
Affiliation
  • Park C; Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro, Bundang-Gu, Seongnam, 13620, Republic of Korea.
  • Suh KJ; Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro, Bundang-Gu, Seongnam, 13620, Republic of Korea.
  • Kim SH; Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro, Bundang-Gu, Seongnam, 13620, Republic of Korea. sehyunkim@snubh.org.
  • Lee KH; Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Republic of Korea.
  • Im SA; Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Republic of Korea.
  • Kim MH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
  • Sohn J; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
  • Jeong JH; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • Jung KH; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • Lee KE; Department of Hematology and Oncology, Ewha Womans University Hospital, Seoul, Korea.
  • Park YH; Hematology-Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
  • Kim HJ; Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
  • Cho EK; Division of Oncology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
  • Choi IS; Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
  • Noh SJ; PentaMedix Co., Ltd, Seongnam, Korea.
  • Shin I; PentaMedix Co., Ltd, Seongnam, Korea.
  • Cho DY; PentaMedix Co., Ltd, Seongnam, Korea.
  • Kim JH; Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro, Bundang-Gu, Seongnam, 13620, Republic of Korea.
Cancer Immunol Immunother ; 73(10): 197, 2024 Aug 06.
Article in En | MEDLINE | ID: mdl-39105849
ABSTRACT

BACKGROUND:

Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863).

METHODS:

We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise.

FINDINGS:

Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months).

INTERPRETATION:

Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Antineoplastic Combined Chemotherapy Protocols / Receptor, ErbB-2 / Transcriptome / Nivolumab / Furans / Ketones Limits: Adult / Aged / Female / Humans / Middle aged Language: En Journal: Cancer Immunol Immunother Journal subject: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Year: 2024 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Antineoplastic Combined Chemotherapy Protocols / Receptor, ErbB-2 / Transcriptome / Nivolumab / Furans / Ketones Limits: Adult / Aged / Female / Humans / Middle aged Language: En Journal: Cancer Immunol Immunother Journal subject: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Year: 2024 Document type: Article Country of publication: