Transient increase in mitochondrial respiration in blood cells from breast cancer patients following chemo- and radiotherapy

Abstract: Mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) has previously been shown to increase after chemo- and radiotherapy in early-stage breast cancer (BC) patients, but the persistence of the increase remains unknown. This study assessed whether changes in mitochondrial respiration and content in PBMCs from postmenopausal BC patients persist up to 1 year after treatment. Thirty-four early-stage BC patients were studied before, shortly after, and six- and twelve-months post-treatment along with 20 healthy controls. Mitochondrial respiration was measured using high-resolution respirometry of intact and permeabilized PBMCs. Mitochondrial content was estimated by quantifying mitochondrial DNA relative to nuclear DNA via qPCR. The mitochondrial respiratory capacity of intact and permeabilized PBMCs from BC patients significantly increased after adjuvant chemo- and radiotherapy (+ 33% and + 30% for the maximal capacity of the electron transport system, ETS), consistent with previous findings. Importantly, the respiratory capacity returned to pre-treatment levels six months after treatment completion in both intact and permeabilized cells (− 23% and − 26% for the ETS). Healthy controls exhibited similar mitochondrial respiration but had increased mitochondrial content (+ 20%) compared to BC patients before treatment. In summary, chemo- and radiotherapy transiently increased mitochondrial respiration in PBMCs, returning to baseline within six months after treatment completion. This temporary rise in oxygen demand may reflect immune system activation.