Preventing initiation of micro metastases from early breast cancer by peri-operative intervention has not been explored adequately. Local anaesthesia blocks voltage gated sodium channels which prevents activation of pro-metastatic pathways. A Cochrane review of using local anaesthesia before surgery for breast cancer concluded inadequate data on its efficacy. We conducted a multi-centre randomized trial to test the impact of peri-tumoral infiltration of local anaesthesia before surgery on survival in women with early breast cancer.
Women with early breast cancer were randomized, to receive peri-tumoral injection of 0.5% lidocaine, 5-10 minutes before surgery (LA arm) or surgery without lidocaine(No-LA arm). Randomisation was stratified by menopausal status and tumour size. Women on neo-adjuvant chemotherapy were not included in the study. Participants underwent breast conservation or modified radical mastectomy and received standard post-operative adjuvant radiotherapy and systemic therapy. The primary endpoint was disease-free survival(DFS) and the secondary endpoint was overall survival(OS).
The study included 1600 patients randomized to LA(N=796) and No-LA(N=804) arms, of whom 1583 were included in the analysis. At 72 months there were 255 DFS events (109 LA arm, 146 No-LA arm). At 6-year DFS were 86.1% and 81.7% in LA and No-LA arms, respectively (HR 0.74, 95% CI 0.58-0.95, p=0.017) and OS were 89.9% and 86.2%, respectively (HR 0.71, 95% CI 0.53-0.94, p=0.019). The impact of LA was similar in subgroups defined by menopausal status, tumour size, lymph node metastases, hormone receptor and HER2neu status. In the LA and no-LA arm, the loco-regional DFS were 94.8% and 92.3%, respectively (HR=0.67, 95%CI 0.45-0.99, p=0.04) and distant DFS were 89.2% and 85.1%, respectively (HR=0.70, 95%CI 0.53 – 0.94, p=0.013). There were no adverse events due to lidocaine injection.
Peri-tumoral injection of lidocaine before surgery is a simple implementable intervention that can reduce 1 of 4 recurrences and 3 of 10 deaths in women with early breast cancer. Altering events at the time of surgery can prevent metastases in women with early breast cancer(CTRI/2014/11/005228).
Clinical trial identification
Legal entity responsible for the study
Tata Memorial Centre, Mumbai, India.
Department of Atomic Energy, Government of India.
All authors have declared no conflicts of interest.