Abstract PO5-17-11: STRATIFICATION OF HIGH GENOMIC RISK IN THE GENETIC SIGNATURE OF 70 GENES (MAMMAPRINT™) IN REAL WORLD ANALYSIS (AGEMA-BRA)
Authors: Fabio Mansani, Ruffo Freitas-Junior
Journal: Cancer Research (2024)

Abstract INTRODUCTION – Although genetic signatures for breast cancer are used to de-escalate chemotherapy treatment, around half of the patients, according to several analyses, present high genomic risk and are conducted in the same way, regardless of the risk score found. The stratification into high risk 1 and high risk 2, proposed in the ISKY-2 cohort, sought to verify the possibility of selecting women with breast cancer who need to escalate the systemic treatment according to the score measured by the MammaPrint™ (MP). OBJECTIVE – To evaluate the outcomes of the AGMA-BRA cohort population (Mammaprint™ genetic signature in the brazilian population), analyzing the characteristics and behavior of patients stratified into high risk 1 (H1) and high risk 2 (H2) by the 70-gene genetic signature. METHODOLOGY – Retrospective study in the AGEMA-BRA cohort with high clinical and genomic risk. They were divided into high risk 1 (H1) with MP score between 0 and &amp;gt; -0.57 and high risk 2 (H2) with MP score ≤ -0.57; analyzing the epidemiological, anatomopathological, immunohistochemical (IHC) profiles and outcomes in the two populations. For the statistical evaluation, a descriptive analysis of the data with absolute and relative frequencies of the variables was performed. To verify the association between qualitative variables, the chi-square test was used. All analyzes were performed in the R 4.1.0 environment (R Core Team, 2021). The AGEMA-BRA study was approved by the ethics and research committee of the State University of Ponta Grossa (CAAE: 12194219.4.0000.0105). RESULTS – The AGEMA-BRA cohort comprises 953 patients with high clinical risk luminal breast cancer, of which 407 (42.7%) are at high genomic risk. After excluding cases that did not contain the necessary information, 176 records were analyzed, with an average follow-up of 40 months. The age group, tumor diameter and number of affected lymph nodes were similar. Statistical significance was observed when evaluating the histological grade where grade 3 was more frequent in cases with the highest risk MP score (H2) with 60% of the records (p. =0.039) (Table 1). As for the IHC analysis, the positivity of estrogen and progesterone receptors, and HER2 did not show statistical significance in the comparison between H1 and H2. In the Ki67 analysis, the comparison with expression &amp;gt;20% was more frequent in population H2 (76.4%) compared to H1 (48.2%) with p.=0.002. Metastasis-free survival (DMFS) was 96.4% for H1 and 95% for H2 (p.=0.269). CONCLUSIONS – The dichotomization of cases with MP score at high risk H1 and high risk H2 in the AGEMA-BRA cohort showed no difference in DMFS, inferring that this classification does not help in the management of these patients. The sample size and short follow-up for a disease that relapses later may have interfered with the result. More robust analysis of these two populations needs to be performed to confirm the presented data. Table 1 - Profile of high genomic risk AGEMA-BRA Citation Format: Fabio Mansani, Ruffo Freitas-Junior. STRATIFICATION OF HIGH GENOMIC RISK IN THE GENETIC SIGNATURE OF 70 GENES (MAMMAPRINT™) IN REAL WORLD ANALYSIS (AGEMA-BRA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-11.