High‐Intensity Focused Ultrasound in Treatment of Primary Breast Cancer: A Systematic Review and Meta‐Analysis

ABSTRACT Background In recent years, tumor management strategies have focused on less invasive methods, aiming to yield optimal efficacy while minimizing further complications and enhancing the overall outcome of patients. High‐intensity focused ultrasound (HIFU), a known thermal ablative technique, has shown promising results in breast cancer treatment. Therefore, we performed this systematic review and meta‐analysis to assess the clinical, histopathologic, immunologic, and radiologic outcomes of HIFU ablative therapy and its complications in patients with primary breast cancer. Methods We searched PubMed and Scopus databases to identify the eligible articles. Data extraction was conducted by two independent authors. A random effects model was employed to pool the proportion of remaining tumor after HIFU therapy in breast cancer. A subgroup analysis was performed according to imaging guidance modality and study design. Moreover, the heterogeneity and bias were assessed using funnel plot, Egger's regression plot, and Baujat plot. Pooled CD4/CD8 ratio mean difference between HIFU and radical mastectomy was measured using a fixed‐effect model. Results We included 26 studies and 677 participants in the systematic review. Tumor necrosis rates varied, with 4 studies reporting less than 50% complete necrosis and 5 more than 50%. Two studies observed HIFU‐induced disturbances in the microvasculature of the targeted tissue. Six noted no contrast enhancement in successfully treated areas, two observed a thin rim indicating necrosis or fibrosis, and four reported a persistent enhancement in MRI images associated with a residual viable tumor. The weighted proportion of patients with residual tumor was 0.59 (95% CI; 0.44–0.73). The subgroup analysis demonstrated that although the pooled proportion of ultrasound‐guided studies was notably higher than magnetic resonance imaging‐guided studies (0.71 vs. 0.57), the between‐group difference was not statistically significant ( p = 0.1693). The diagnostic tools showed that the results are driven by certain studies, and there is also a potential small‐study effect. Furthermore, the CD4/CD8 ratio was higher in the HIFU group, with a weighted mean difference of 0.6 (95% CI: 0.41–0.78). The most prevalent side effects were pain (47.14%) and skin burn (2.59%). Conclusions HIFU is a relatively safe procedure for the treatment of breast cancer as an independent or conjugated therapy and its effectiveness is promising regarding histopathological response, immunological reactivity, and vascular damage in the targeted area.