Preclinical hyperthermia (HT) research helps uncover heat-induced signaling pathways and improve synergy of anticancer therapies. This pilot study investigates the safety and feasibility of targeted delivery of fractionated HT in mouse xenografts with triple-negative breast cancer using our 2.45 GHz microwave preclinical system. Numerical simulations of the HT applicator on mouse model indicated 98% target coverage for tumors ≤700 \(\:{\text{m}\text{m}}^{3}\). HT experiment in healthy mice using invasive temperature probe established the safe power level for localized HT in tumor bearing mice. Mice with tumor volumes below 700 \(\:{\text{m}\text{m}}^{3}\) were divided into treatment and control groups (two per group) in the pilot study. Treatment group received six fractions of HT lasting 45 min each, with 48-hour interval between fractions. Tumor growth was monitored using caliper and treatment effects were assessed in terms of health status and histopathology. Mice body weight gain was stable (26–26.5 g) and no adverse effects were observed in both groups. Tumor growth in HT group reduced by 43% compared to controls. Histological analysis revealed significantly greater tumor damage in treated mice (40–70%) versus controls (5–10%). It is concluded that the preclinical system is robust for carrying out detailed preclinical investigations on HT induced thermal response mechanisms and combining HT with anticancer combination therapies.
