Abstract P2-11-18: Serum methylmalonic acid concentrations at breast cancer diagnosis are not associated with distant metastases

Abstract

Introduction: Methylmalonic acid (MMA), a metabolite and by-product of propionate metabolism, promotes breast cancer (BC) progression in mice via the transforming growth factor-beta (TGFβ) signaling pathway (Gomes et al, Nature 2020). It is currently unknown if this effect also exists in patients with BC. Objectives: To investigate the association between baseline serum MMA concentrations in patients at BC diagnosis and development of distant metastases via a matched case-control study. Methods: We included 32 patients with early Luminal B-like BC (Lumb, median age 62.4y) and 52 patients with early triple-negative BC (TNBC, median age 50.5y) who developed distant metastases within 5 years. They were matched to an equal number of early BC patients with at least 5 years of follow-up (median age 62.2y for Lumb and 50.5y for TNBC) who did not develop distant metastases with at least 5 years of follow-up. Matching was performed based on age at diagnosis date (± 5y), tumor stage, and treatment received ((neo)adjuvant chemotherapy and radiotherapy, yes/no). Serum MMA concentrations were determined by liquid chromatography with tandem mass spectrometry (LC-MS-MS). Summary statistics, paired analyses, and multiple conditional logistic regression analyses were performed with and without adjusting for potential covariates (age, kidney function, and tumor stage). Results: Baseline serum MMA at BC diagnosis significantly correlated with age (rs=0.35, p=.005 in Lumb; rs=0.35, p=.0003 in TNBC), and negatively correlated with kidney function assessed by estimated glomerular filtration rate (eGFR, rs= -0.42, p=.0005 in Lumb; rs= -0.32, p=.0009 in TNBC). MMA concentrations at diagnosis were not associated with distant metastases in either subtype, after adjusting for kidney function, age, and tumor stage (all p>.05). Next, we categorized BC cases in the public TCGA (n=174 for Lumb; n=140 for TNBC), METABRIC (n=461 for Lumb; n=199 for TNBC), and GSE25066 (n=78 for Lumb; n=182 for TNBC) database according to their 5-year metastatic status, and analyzed the TGFβ signaling pathway activity of primary BC. Like MMA concentrations, a gene expression signature of TGFβ signaling was not associated with distant metastases in patients with BC. Conclusion: Baseline serum MMA concentrations and a gene signature for TGFβ signaling at BC diagnosis are not associated with distant metastases among patients with Lumb and TNBC subtypes. Citation Format: Qi Wu, Sigrid Hatse, Juan F. García, Patricia Altea-Manzano, Jaak Billen, Mélanie Planque, Anke Vandekeere, Yentl Lambrechts, François Richard, Annouschka Laenen, Kevin Punie, Patrick Neven, Ines Nevelsteen, Giuseppe Floris, Christine Desmedt, Ana Gomes, Sarah-Maria Fendt, Hans Wildiers. Serum methylmalonic acid concentrations at breast cancer diagnosis are not associated with distant metastases [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-18.