KEY TAKEAWAYS
- REGISTEM, an observational study, aimed to investigate oncogenic drivers in ctDNA during relapse in patients with luminal BC and early or late distant recurrence.
- Pts with HR-positive BC and metastatic relapse were selected for the study. ctDNA was analyzed using AVENIO assay to identify genomic aberrations.
- The study found early and late distant relapses in BC were different regarding clinical presentation and genomic profile.
Patients (pts) with hormone receptor-positive early breast cancer can relapse months to decades after surgery, but the causes of early vs late relapses are poorly understood. Researchers aimed to investigate oncogenic drivers in circulating tumor DNA (ctDNA) during relapse in pts with luminal breast cancer (BC) and early or late distant recurrence.
The study analyzed the pts with HR-positive BC who relapsed early or late and had ctDNA with AVENIO assay for genomic aberrations.
They included 84 pts, 36 in the early metastatic relapse (early-R) group, and 48 in the late metastatic relapse (late-R) group. The median time to relapse was shorter in early-R (24.97 months) than in late-R (151.84 months). The time from the last adjuvant ET dose to relapse was brief in early-R (0.03 months) and extended in late-R (74.06 months). The median PFS to first-line treatment was 7.62 months (early-R) and 35.15 months (late-R). Median overall survival (OS) after metastatic diagnosis was 27.74 months (early-R) and not reached (late-R) in 32.08 months of follow-up.
In ctDNA analysis, mutations were found in 85% of patients (89% early-R, 81% late-R). Early-R had higher TP53 (44% vs. 19%), ESR1 (11% vs. 4%), MAPK_ERK pathway (14% vs. 6%), and ERBB2 copy number alterations (25% vs. 2%) rates. PI3K/AKT alterations were similar (38% vs. 42%) and unrelated to OS. ESR1 mutations (mMAF: early 0.64%, late 0.4%) were tied to worse OS (wild-type median OS 48.48 months, mutant 12.84 months; P= 0.0025). Around 10 pts exhibited ERBB2 copy number alterations (CNA) upon metastatic relapse: 9 (25%) in the early-relapse and one patient (2%) in the late-relapse group. Among them, 7 pts (70%) were HER2-positive. Pts with ctDNA ERBB2 CNA had worse OS (median OS of 48.48 months for wild-type vs. 20.52 months for mutants; adjusted P-value = 0.025).
The study found early distant relapse in luminal BC is more aggressive and has more actionable genetic alterations.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.1060
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02819882
Angel Guerrero, Isabel Alvarez, Ariadna Tibau, Josefina Cruz Jurado, César A Rodríguez Sánchez, Purificacion Martinez, Catalina Falo, Maria Hernández Sosa, Mireia Margelí, Ana Miguel, Jose Ignacio Chacon, Raquel Andres, Encarna Adrover, Miguel Corbellas Aparicio, Rosalia Caballero, Jesus Herranz, Daniel Fernández García, Silvia Antolín Novoa, Sara López-Tarruella, and Federico Rojo. DOI: 10.1200/JCO.2023.41.16_suppl.1060 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 1060-1060.
