Abstract P1-11-07: Associations between Breast Cancer Index Classifications and MSK-IMPACT Genomic Profiles in HR+/HER2- Breast Cancer

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Abstract Background: The Breast Cancer Index (BCI) is a gene expression-based signature that stratifies patients based on the risk of overall (0-10 years) and late (post-5 years) distant recurrence (DR). BCI also predicts the likelihood of benefit from extended endocrine therapy in early-stage, HR+ breast cancer (BC). This study aims to explore the correlation between BCI and disease-free interval and possible associations between gene-expression-based classification by BCI and the genomic features of primary breast cancers in patients with HR+/HER2- breast cancer who developed metastatic relapse. Methods: Primary tumor samples from HR+/HER2- metastatic/recurrent BC patients underwent both BCI and MSK-IMPACT targeted sequencing. MSK-IMPACT identifies somatic mutations, rearrangements, and copy-number alterations in up to 505 cancer genes. Time to DR (TTDR) defined as the time between date of surgery and distant recurrence. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to evaluate BCI's prognostic performance. Pearson’s correlation (R) was used for correlation between BCI score and TTDR. Fisher’s exact tests were used to identify genomic alterations with significant differences comparing BCI prognostic groups. Due to small sample size, comparisons were not adjusted for multiple testing. Results: The study includes 107 HR+/HER2- metastatic patients with primary tumors tested with both MSK-IMPACT and BCI: 44% post-menopausal, 60% T2/3, 64% grade 3, 56% lymph node positive (LN+). Consistent with the nature of this cohort (all experienced DR), BCI classified the majority of the patients (n=94, 88%) as high-risk for DR. The BCI score was negatively correlated with TTDR (R=-0.24, p=0.011). Patients classified as high-risk by BCI tended to have DR earlier than low-risk patients (median TTDR: 2.8y vs. 3.4y; HR=1.95 with 95% CI: 1.05-3.62; p=0.031). Overall, the genomic profile of the cohort was consistent with high-risk luminal primary tumors, with higher than expected rate of TP53 mutations (35%). Analysis of somatic genomic alterations by MSK-IMPACT revealed a trend that there are more mutations in PIK3CA and TBX3 in the BCI low-risk group compared to the high-risk group (77% vs 46%, p=0.038) and (38 vs 3%, p=0.020), respectively. Conclusion: In this cohort of high-risk BC patients who all had a DR event, BCI remained prognostic with lower BCI scores associated with longer TTDR. Initial findings from the genomic correlative analysis suggested an association of BCI with certain genomic features. Further analyses with additional samples are ongoing to substantiate these findings. Citation Format: Hong Zhang, Li Ma, Anton Safonov, Natalia Siuliukina, Julia Ah-Reum An, Subhiksha Nandakumar, Enrico Moiso, Edaise da Silva, Mehnaj Ahmed, Lisa Loudon, Konner Nelson, Kevin Murphy, Jade Oghoanina, Mark Robson, Sarat Chandarlapaty, George Plitas, Yi Zhang, Kai Treuner, Pedram Razavi. Associations between Breast Cancer Index Classifications and MSK-IMPACT Genomic Profiles in HR+/HER2- 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 P1-11-07.

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