Abstract PO2-01-13: Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women

Abstract

Abstract Introduction Premenopausal women diagnosed with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) face a significantly higher risk of cancer recurrence and mortality compared to older women, particularly those diagnosed under the age of 40. The underlying causes behind this disparity remain largely unknown. Material and methods We retrospectively select tumour samples from patients (pts) diagnosed with HR+/HER2- EBC at Hospital Clinic (Barcelona, Spain) from May 2014 to March 2020 who had a PAM50/Prosigna assay (Veracyte) previously performed. This assay examines the expression of 50 genes involved in important breast cancer signaling pathways, as well as the intrinsic subtypes (IS) and the Risk of Recurrence (ROR) score. Our primary objective was to compare the distinct clinicopathological and molecular characteristics of HR+/HER2- EBC between two age groups: patients under 40 years old (Young EBC or YEBC) and those 40 years old and above (Older EBC or OEBC). Disease-free survival (DFS) was defined as the time between diagnosis and the first recurrence. Comparisons between groups were carried out using chi-square tests (categorical variables). Additionally, we performed a two-class unpaired Significance Analysis of Microarrays (SAM) with a false discovery rate (FDR) less than 5% to identify genes with significantly different expression between YEBC and OEBC. The statistical significance level was set at less than 0.05. Results A total of 441 tumor samples from 420 patients were included in the analysis, with 5% (22/441) corresponding to YEBC. With a median follow-up of 64.5 months, there were 20 breast cancer (BC) recurrences (4.8%), 12 second cancers (2.9%) and 5 BC-related deaths (1.2%), all occurring in the OEBC group. Table 1 provides an overview of the main clinico-pathological and molecular characteristics. YEBC tended to have larger tumors, with 45.5% (10/22) measuring over 2 cm compared to 36.1% (151/419) in OEBC (p=0.376). YEBC also had a higher proportion of grade 3 tumors (18.18% versus 3.1% in OEBC, p=0.418) and lower expression of estrogen receptor (ER) as determined by immunohistochemistry (mean of 72.28% vs 88.36%, p=0.004). Regarding the PAM50 IS, there was a difference observed between YEBC and OEBC (p < 0.001). Specifically, YEBC patients exhibited a tendency towards a higher proportion of Luminal B tumors (54.6% versus 38.9% in OEBC, p=0.144), as well as non-Luminal subtypes such as Basal-like (18.2% versus 0.95% in OEBC, p< 0.001) and HER2E (4.6% versus 0.7% in OEBC, p=0.186). YEBC tended to have higher ROR (p=0.167), and to receive chemotherapy in a higher proportion, especially in the intermediate-risk group (p=0.004). In YEBC tumours, SAM analysis (p < 0.05) showed an overexpression of genes mainly related with proliferation (i.e., RRM2, MELK, MIK67), cell cycle progression (i.e., KNTC2, CDC20, MYBL2) and apoptosis inhibition (i.e., BIRC5). In OEBC there were an overexpression of genes related with the oestrogen receptor-signalling pathway (i.e., ESR1, NAT1, FOXA1, PGR). Luminal B tumours in YEBC showed an upregulation of genes related to proliferation, migration, and poor prognosis (i.e., KRT17, KRT5) compared to OEBC. However, since there were no recurrences in the YEBC group, differences in terms of DFS between the groups could not be calculated. Principio del formulario Final del formulario Conclusions YEBC exhibited a more advanced stage and a more aggressive intrinsic phenotype compared to OEBC. Additionally, these tumors showed a tendency to upregulate genes involved in proliferation, cell cycle progression, and survival, while downregulating genes related to hormone signaling pathways. These molecular characteristics may help explain the worse prognosis of YEBC compared to OEBC. However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies Citation Format: Francisco Javier Muñoz-Carrillo, José Antonio Sola, Carme Crous, Esther Sanfeliu, Isabel Garcia-Fructuoso, Elia Seguí, Teresa Gorría, Raquel Gómez-Bravo, Barbara Adamo, Tomás Pascual, Olga Martínez-Sáez, Francesco Schettini, Pablo Rivera, Rosalía Cayuela, Montserrat Muñoz, Núria Chic, Maria Vidal. Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women [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 PO2-01-13.