A new prospective randomized trial suggests that injecting lidocaine around a breast tumor prior to surgical removal may reduce the risk of metastasis and death in patients with early-stage breast cancer.
This promising technique, in both preclinical and clinical settings, was associated with significant improvements, showing relative risk reductions of 26% in 5-year disease-free survival and 29% in overall survival.
Tessa Higgins, BA (Brigham and Women's Hospital, Boston), and Elizabeth A. Mittendorf, MD, PhD (Dana-Farber Brigham Cancer Center and Harvard Medical School, Boston), wrote in an accompanying editorial, "These findings support the use of peritumoral lidocaine as a low-cost intervention that can be easily incorporated into the management of patients with breast cancer."
Considering an estimated 2.3 million new cancer cases are diagnosed globally each year—half of which involve operable disease—peritumoral local anesthetic use during surgery is estimated to potentially save more than 100,000 lives annually.
The study and editorial were published online on April 6 in the Journal of Clinical Oncology.
Research on perioperative interventions to prevent metastasis is insufficient, but there is a scientific basis for using local anesthesia for this purpose. The study authors explained that local anesthetics have been found to block voltage-gated sodium channels, which can inhibit metastatic pathways.
However, findings from retrospective studies have been mixed; while some indicate better outcomes for patients receiving regional or local anesthesia during primary breast cancer surgery, others do not.
The team randomized 1,583 women with early-stage breast cancer who had not previously received neoadjuvant therapy from 11 centers in India to receive either up to 4.5 mg/kg of 0.5% lidocaine (n = 786) or no lidocaine (n = 797). After general anesthesia was administered, lidocaine was injected into all tumor surfaces, and surgery began 7-10 minutes after the injection.
All patients received standard postoperative adjuvant therapy, and no side effects associated with the lidocaine injection were reported.
During a median follow-up of 68 months after mastectomy or breast-conserving surgery, 5-year disease-free survival rates were 86.6% in the lidocaine group and 82.6% in the group without lidocaine (hazard ratio [HR], 0.74; P = .017). Five-year overall survival rates also improved significantly for those receiving lidocaine: 90.1% versus 86.4% (HR, 0.71; P = .019).
The authors also found that the 5-year cumulative incidence rates of locoregional recurrence were significantly lower in those receiving lidocaine—3.4% versus 4.5% (HR, 0.68)—as were rates of distant recurrence: 8.5% versus 11.6% (HR, 0.73).
The effect of lidocaine use was not significantly different in patients undergoing mastectomy (HR, 0.73) versus breast-conserving surgery (HR, 0.70).
Researchers observed that the benefits of lidocaine in the overall study population were consistent across subgroups defined by menopausal status, tumor size, nodal metastases, hormone receptor status, and HER-2 status.
The authors wrote, "Whatever the mechanisms, the results of this study suggest a potential role for modulating processes during surgery that enable metastatic potential in breast cancer cells to reduce the onset of metastases and improve surgical outcomes."
They noted that due to a revision in the study design, the final absolute difference of 4% achieved between the two groups was less than the planned 6%. Nevertheless, they added, "The absolute 4% difference in disease-free survival, alongside a 3.7% absolute overall survival benefit and a 26% relative risk reduction in the context of current advances in the adjuvant setting for breast cancer, makes the potential clinical utility of this intervention highly appealing."
Editors agreed that the perioperative use of local anesthetics "has the potential to reduce recurrence and mortality rates in women with early-stage breast cancer," and noted that implementing this simple, cost-effective intervention would be "reasonable."
