Abstract P3-05-24: Mapping the Genomic Landscape: Comprehensive Profiling of Diverse Histological Types of Breast Cancer

Abstract Introduction: Breast Cancer (BC) is a highly heterogeneous tumor consisting of various histological types. Data on genomic alterations (GAs) in special types of breast cancer, which account for about 10% of all breast cancers, remain limited. We aimed to clarify genomic profiles of BC, especially focusing on breast cancer of special type. Methods: We retrospectively reviewed data on female patients with unserectable/metastatic BC who underwent comprehensive genomic profiling (CGP) tests and were registered for the Center for Cancer Genomics and Advanced Therapeutics in Japan from June 2019 to June 2024. CGP tests were conducted by NCC Oncopanel System, FoundationOne CDx (F1CDx), or GenMineTOP. We examined somatic GAs, microsatellite instability (MSI) status, and tumor mutation burden (TMB) of BC. TMB-high was defined as ≥10 mutations/Mb. Actionable GAs were counted if they were classified as “pathogenic/oncogenic” or “likely pathogenic/likely oncogenic variants”. Druggable GAs were defined as actionable GAs that are the targets of drugs approved for BC or other types of cancer, or that have been shown to be effective in clinical trials for BC or other types of cancer. Results: 3763 patients were identified, of which cases in which detailed histology could not be determined or non-epithelioid tumors were excluded, and finally 2915 patients were included in the analysis. The most used CGP test showed F1CDx (89.7%). Histological types included invasive ductal carcinoma (IDC), invasive breast cancer of no special type (IBC-NST), invasive lobular carcinoma (ILC), metaplastic carcinoma (MpBC), mucinous carcinoma (MuBC), solid papillary carcinoma, adenoid cystic carcinoma (ACC), inflammatory breast cancer (IBC), secretory carcinoma (SBC). The number of each histological subtypes were 2212, 410, 169, 81, 22, 7, 6, 6 and 2, respectively. There were statistically significant differences regarding the PI3K/AKT/mTOR pathway (IDC vs ILC: 57.8% vs 72.8%; p = 0.0045, IBC-NST vs ILC: 55.4% vs 72.8%; p = 0.0031) and BRCA1/2 alterations (IDC vs ILC: 8.7% vs 4.1%; p = 0.039). The frequency of ESR1 alterations was the highest in mucinous carcinoma (36.4%), and the lowest in ACC, MpBC, IBC, and SBC (all of them: 0%), but did not show statistically significant differences by histological type. The proportions of MSI-high and TMB-high were the highest in ILC (1.2% and 18.3%, respectively), but the differences were not statistically significant by histological type. The frequency of druggable GAs was the highest in SBC (100% for NTRK fusion), and the lowest in ACC (33.3%), but did not show statistically significant differences. Conclusions: Despite the limited number of cases in some histological types, this study revealed genomic characterizations among many histological types of BC. This information will provide an important basis for considering genome-based precision medicine in the future. Citation Format: Taro Yamanaka, Tatsunori Shimoi, Mai Onishi, Rui Kitadai, Mai Hoshino, Munehiro Ito, Ayumi Saito, Shosuke Kita, Asuka Kawachi, Hitomi Sumiyoshi-Okuma, Aiko Maejima, Yuki Kojima, Kazuki Sudo, Emi Noguchi, Yasuhiro Fujiwara, Takafumi Koyama, Kan Yonemori. Mapping the Genomic Landscape: Comprehensive Profiling of Diverse Histological Types of Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-05-24.