Clinical Research Directory

Peritumoral and Periganglionic Infiltration of Levobupivacaine Prior to Conservative Surgery for Triple-negative Breast Cancer

Sponsor: Institut Jean-Godinot

Summary

Breast cancer is one of the most common cancers among women. One in eight women in France will develop breast cancer during their lifetime (Inca). In 2023, 61,214 new cases of breast cancer were diagnosed in France, and in 2018, 12,146 deaths were attributed to this disease (e-cancer). Triple-negative breast cancer is characterised by the absence of hormone receptors (progesterone and oestrogen) and the HER2 protein on the surface of its cells. It is the breast cancer with the highest risk of recurrence, with a progression-free survival rate of 62% at 2 years (Di Lisa et al, 2023). In vitro, local anaesthetics have been shown to have breast tumour cytotoxicity, according to Borgeat in 2012. Among the various local anaesthetics tested in vitro, levobupivacaine has been shown to have the highest breast tumour cytotoxicity, according to Zhi-Fu Wu in 2022. At doses below systemic toxicity thresholds and at concentrations routinely used, levobupivacaine induces greater apoptosis and reduces the metabolic activity of breast tumour cells to a greater extent than lidocaine. Levobupivacaine has an antitumour effect on MDA-MB-31 cells, according to Zhi-Fu Wu in 2022. MDA-MB-31 cells overexpress the voltage-gated sodium channel (VGSC). The VGSC is composed of different subunits, including the Nav1.5 α subunit, which can be inactivated by levobupivacaine. In breast cancer, VGSC is mainly overexpressed in metastatic cancers and in the triple-negative line. The Nav1.5 α subunit of VGSC plays a role in tumour cell growth and migration. In vitro, a decrease in MDA-MB-231 cell migration has been demonstrated with levobupivacaine. Inactivation of Nav1.5 α with a molecule other than levobupivacaine (e.g., phenytoin) has shown antitumour effects in vitro and in vivo (Chen et al, 2022). Targeting VGSC using a well-characterised local anaesthetic such as levobupivacaine could be a strategy for reducing the metastatic risk of triple-negative breast cancers, especially since surgical infiltration of local anaesthetics is a commonly performed procedure within the scope of their marketing authorisation. Badwe et al. (2023) demonstrated a benefit of peritumoral injection of 0.5% lidocaine on overall survival and progression-free survival in women with operable breast cancer. However, in this study, the type of surgery varied (lumpectomy or mastectomy) and only a peritumoral injection was performed (without periganglionic injection). Furthermore, no specific analysis of the triple-negative breast cancer subgroup was presented. Targeting VGSC using a well-characterised local anaesthetic such as levobupivacaine could be a strategy for reducing the metastatic risk of triple-negative breast cancers, especially since surgical infiltration of local anaesthetics is a procedure commonly performed within the scope of their marketing authorisation. Badwe et al. Furthermore, no specific analysis of the triple-negative breast cancer subgroup was presented. Thus, no high-level evidence (prospective, randomised, double-blind) studies have been conducted on the benefits of peritumoral and periganglionic levobupivacaine infiltration in the context of conservative surgery (lumpectomy) for triple-negative breast cancer. The literature only contains in vitro studies, retrospective studies and a few rare prospective studies that were not conducted blind

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