Phase II trial of delta-tocotrienol in neoadjuvant breast cancer with evaluation of treatment response using ctDNA

Abstract

Neoadjuvant treatment of breast cancer is applied to an increasing extent, but treatment response varies and side effects pose a challenge. The vitamin E isoform delta-tocotrienol might enhance the efficacy of chemotherapy and reduce the risk of side effects. The aim of this study was to investigate the clinical effect of delta-tocotrienol combined with standard neoadjuvant treatment and the possible association between detectable circulating tumor DNA (ctDNA) during and after neoadjuvant treatment with pathological treatment response. This open-label, randomized phase II trial included 80 women with newly diagnosed, histologically verified breast cancer randomized to standard neoadjuvant treatment alone or in combination with delta-tocotrienol. There was no difference in the response rate or frequency of serious adverse events between the two arms. We developed a multiplex digital droplet polymerase chain reaction (ddPCR) assay for the detection of ctDNA in breast cancer patients that targets a combination of two methylations specific for breast tissue (LMX1B and ZNF296) and one cancer specific methylation (HOXA9). The sensitivity of the assay increased when the cancer specific marker was combined with the ones specific to breast tissue (p < 0.001). The results did not show any association between ctDNA status and pathological treatment response, neither at midterm nor before surgery.

Analysis and validation of critical signatures and immune cell infiltration characteristics in doxorubicin-induced cardiotoxicity by integrating bioinformatics and machine learning

“…40 Previous evidence suggests that ZNF296 is an effective biomarker for breast cancer detection. 41 Furthermore, recent studies have found that ZNF296 is a regulator of H3K9me3 and is closely associated with the pluripotency of embryonic stem cells. 42 Another study indicated that ZNF296 was associated with the formation of induced pluripotent stem (iPS) cells.…”

Different Roles of Tocopherols and Tocotrienols in Chemoprevention and Treatment of Prostate Cancer

“…Similarly, Kjaer et al. [ 152 ] reported that δTE at 300 mg thrice a day did not enhance the efficacy of neoadjuvant breast cancer treatment or reduce the frequency of side effects in a phase II trial involving 80 patients with newly diagnosed breast cancer (NCT02909751). On the contrary, δTE at daily 400–1600 mg induced apoptosis in dysplastic or malignant pancreatic tissues in a phase I trial including 25 patients for curative surgical resection with presumptive premalignant or malignant neoplasms of exocrine pancreas (NCT00985777) [ 25 ].…”