480P - Prognostic significance of somatic DNA gene rearrangement and structural atypia in metastatic breast cancer

Background

Comprehensive genomic profiling (CGP) testing for breast cancer has become widely used to identify genetic alterations, including somatic DNA gene rearrangement and structural atypia. The prognostic impact of somatic DNA gene rearrangement/structural atypia in metastatic breast cancer (MBC) is unclear. In this study, we aimed to clarify the prognostic significance of DNA gene rearrangement and structural atypia.

Methods

We evaluated 1790 cases of MBC who received cancer gene panel tests under the national health insurance system using FoundationOne CDx(R) between June 2019 and October 2022. Genomic and clinical data were collected from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) Research-Use Portal in Japan. Patients were divided into two groups based on the presence or absence of somatic DNA gene rearrangement/structural atypia described in the reports: the rearrangement group (with at least one DNA gene rearrangement/structural atypia) and the others (without). Genomic alterations and overall survival from the date of diagnosis were evaluated.

Results

One hundred sixty-four patients (9.2%) had one or more DNA gene rearrangements or structural atypia. Overall, 285 DNA gene rearrangements/structural variants were found, with FGFR1 rearrangement being the most common (n=10), followed by MTOR rearrangement (n=7), FGFR2 rearrangement (n=6), NOTCH2 rearrangement (n =5). The rearrangement group had significantly better overall survival than the others (rearrangement group, NA, the others, 162.3m; log-rank P-value = 0.0006; hazard ratio, 0. 43; 95% confidence interval, 0.26-0.71).

Conclusions

MBC patients with one or more DNA gene rearrangements and structural atypia had a significantly better prognosis. Further investigations of the prognostic and biological significance of these alterations in MBC patients are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

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