163P - Impact of genomic sequencing data on treatment decisions in advanced breast cancer (ABC)

Background

Next generation sequencing (NGS) technologies allow for a better understanding of tumors’ biology and the implementation of targeted therapy (TT). We conducted a prospective investigational project at the Catalan Institut of Oncology-Badalona to assess their clinical utility in ABC.

Methods

After obtaining the informed consent of patients (pts) with ABC, Oncomine Comprehensive AssayV3 and the Intrinsic subtype (IS) by Prosigna were applied to analyze genomic profile including mutations (mut) and copy number variants (CNV) of 161 genes. We evaluated clinical and molecular characteristics, TT and the impact of molecular alterations (alt) on treatment decision.

Results

Since November 2021, 64 pts were included, with evaluable genomic results in 54 (29 metastasis and 25 primary tumors). Median age was 59y (37-82). Twenty-three out of 53 (43.4%) pts with hormonal receptor (HR) positive HER2-negative ABC had been treated with >1 line (L) hormone therapy. Thirty-three pts (51.6%) had not received any prior chemotherapy L, 18 (28.1%) 1L, and 13 (20.3%) 2L. The IS distribution was 24 (44.4%) luminal B, 20 (37%) luminal A, 5 HER2-enriched, 5 basal-like (9.3% each), concordant with surrogate subtypes by IHQ in 70.6 %. More than 60 molecular alt were identified in 35 genes (median of 2 alt/patient); 1) mut: 21 (38.8 %) in PI3KCA (84.2% in HR+/HER2- tumors) and 17 (31.5%) in TP53 and 2) CNVs: 14 (25.9%) in FGFR1 and 13 in FGF19 (24%), 12 in CCND1 and ERBB2 (17.7% each). PI3KCA-mut was associated with a lower incidence of other alt compared to non-mut tumors (15 vs 52 additional alt, respectively: Chi-square, p=0.001). Six pts had died at the time of analysis with a median Overall Survival (OS) of 3.4 years. Triple Negative ABC, TP53 and PTEN mut were independently associated with worse progression free survival to 1L and OS (p<0.001). To date, 6 pts (11.1%) have received TT, mainly for PI3KCA mut and up to 25 (39.1%) will be considered for TT at progression.

Conclusions

Based on NGS data, more than 10% of pts benefitted from targeted therapy at the time of analysis, with expected benefit for additional 20%. Noteworthy, NGS adds prognostic information and better selection of sequential therapies. NGS is a key tool for personalised therapies in ABC, requiring more research to optimize its use.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Hospital Germans Trias i Pujol.

Disclosure

M.A. Bergamino: Non-Financial Interests, Personal, Invited Speaker: Eisai; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Funding: Novartis.M. Romeo Marin: Financial Interests, Personal, Funding: GSK, AstraZeneca, Clovis, MSD. M. Margeli Vila: Financial Interests, Personal, Funding: Novartis, Pfizer, Lilly, Gilead, Pierre Fabre, MSD. All other authors have declared no conflicts of interest.