497P - Metastatic potential of the somatic alteration associated with TCA-cycle in breast cancer

Background

Cancer metastasis is considered to occur through a complicated process in which cancer cells from the primary tumor migrate via the vascular and lymphatic systems. The mechanism of metastasis has previously been focused on the expression of molecules; however, their ability to form metastasis, and metastatic potential to target organs remains unknown. Because glucose metabolism is essentially active in brain tissue, FDG is substantially accumulated even in normal tissue. As a consequence, it is absolutely necessary for cancer cells to have the ability to survive in the brain microenvironment, in which glucose is unavailable. In this study, we investigated whether metabolic reprogramming of the TCA cycle, which enables energy production from sources other than glucose, plays a pivotal role in forming brain metastases (BM).

Methods

The genomic information was obtained from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) Research-Use Portal. 2,629 cases of MBC who received cancer gene panel testing (Foundation One CDx (R)) between June 2019 and October 2022 were subjected to this analysis. The relationship between the somatic alteration associated with the TCA-cycle (TCA-alteration) and overall survival (OS) or BM incidence was examined.

Results

221 patients (8.4%) had TCA-alteration. The median of OS was 6,217 days in TCA-alteration and 5,050 days in others (log-rank p=0.8377, n.s). TCA-alteration was discovered in 27 of 243 BM patients (11.1%) and 194 of 2,386 non-BM cases (8.1%) (p=0.11, n.s).

Conclusions

Despite the fact that metabolic reprogramming is necessary for metastatic potential, there was no significant difference in survival or the incidence of BM and TCA-alterations. In addition to genetic profiling, a metabolic approach will be necessary to understand the metabolic tumor microenvironment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

N.S. Harada.

Funding

Has not received any funding.

Disclosure

N.S. Harada: Non-Financial Interests, Personal, Speaker’s Bureau: Lilly, Chugai Pharma, Kyowa Kirin, AstraZeneca, Novartis, Pfizer, Takeda, Eisai. H. Tada: Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Lilly, Pfizer, Chugai Pharma, Daiichi Sankyo, MSD, Novartis, Kyowa Kirin, Takeda. M. Miyashita: Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Lilly, Pfizer, Chugai Pharma, Taiho Oncology, Eisai, MSD. A. Ebata: Non-Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin. M. Sato: Non-Financial Interests, Personal, Speaker’s Bureau: Lilly, Chugai Pharma. T. Ishida: Non-Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, Lilly. All other authors have declared no conflicts of interest.