Abstract
BackgroundBreast cancer treatment is tailored to the specific cancer subtype. Often, systemic treatment is given prior to surgery. Chemotherapy induces significant endoplasmic reticulum (ER) stress-mediated cell death and upregulation of 78-kDa glucose-regulated protein (GRP78). We hypothesized that chemotherapy induces ER stress not only in the tumor tissue but also in immune cells, which may affect the response to anti-cancer treatment.MethodsWe determined the surface expression of GRP78 on 15 different peripheral blood mononuclear cell (PBMC) subpopulations in 20 breast cancer patients at three time points of the neoadjuvant treatment, i.e., at baseline, after anthracycline treatment, and after taxanes treatment. For this purpose, we performed flow cytometric analyses and analyzed the data using ANOVA and the Tukey test. Serum cytokine levels were also evaluated, and their levels were correlated with response to treatment using the t-test after log transformation and Mann-Whitney U Wilcoxon W test.ResultsA significant increase in GRP78 expression in PBMCs was documented during the taxane phase, only in patients who achieved pathological complete response (pCR). GRP78-positive clones correlated with increased serum levels of interferon gamma (IFNγ).ConclusionsThe presence of GRP78-positive clones in certain PBMC subpopulations in pCR patients suggests a dynamic interaction between ER stress and immune responsiveness. The correlation of GRP78-positive clones with increased levels of IFNγ supports the idea that GRP78 expression in PBMCs might serve as a new predictive marker to identify the possible benefits of taxanes in the neoadjuvant setting.
Highlights
Breast cancer treatment is tailored to the specific cancer subtype
Cell surface expression of 78-kDa glucose-regulated protein (GRP78) in peripheral blood mononuclear cell (PBMC) We first observed that the percentage of T, natural killer (NK) and monocytes sub-populations vary between PBMCs of breast cancer patients before and after chemotherapy
We determined the baseline (P1) GRP78 expression in 15 different PBMC subpopulations derived from patients with breast cancer prior to any treatment and in healthy women
Summary
Breast cancer treatment is tailored to the specific cancer subtype. Often, systemic treatment is given prior to surgery. An increasing number of patients are subjected to systemic treatment prior to surgery as part of the standard of care or a clinical trial [5] This is considered a window of opportunity for treatment optimization [6]. Most of the patients who need chemotherapy in this setting will be offered a regimen that contains anthracyclines and taxanes [7, 8]. These two agents are considered fundamental in breast cancer treatment, they are beneficial only in some patients and are associated with high toxicity [9, 10]. The magnitude of response to neoadjuvant treatment strongly correlates with patient prognosis after surgery; an optimal result is achieved when no residual invasive disease is detected and is determined as pathological complete response (pCR) [11, 12]
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