Abstract
Introduction: This study compared the efficacy, complications, and related indicators of High-Intensity Focused Ultrasound Ablation (HIFU) and Radiofrequency Ablation (RFA) for treating benign breast tumors, aiming to provide effective evidence-based support for clinical practice. Methods: This study is a retrospective study. A retrospective analysis was conducted on data from patients undergoing thermal ablation surgery at The First Affiliated Hospital of Gannan Medical University between February 2021 and May 2024, divided into the HIFU group (147 cases, 231 tumors) and the RFA group (151 cases, 193 tumors), with perioperative indicators, postoperative efficacy, effective ablation rate, complications, prognosis, and satisfaction statistically analyzed. Results: The groups showed no significant differences in age, BMI, tumor diameter/volume, or proportion of tumors across size categories, ensuring comparability. Operative time was shorter for HIFU than RFA (p < 0.005), though hospital stay was longer for HIFU (p < 0.05). Intra/postoperative pain was lower in the HIFU group (p < 0.05). At 6 months post-op, volume reduction was greater with HIFU (p < 0.05); specifically, for tumors ≤1 cm no significant difference existed (p > 0.05), but for tumors >1–2 cm and >2–3 cm, HIFU showed superior volume reduction (p < 0.05). Overall volume change favored HIFU (p < 0.05). The effective ablation rate at 6 months was significantly higher for HIFU (p < 0.05), including for multiple lesions (p < 0.05). Postoperative pain scores (NRS) were significantly lower with HIFU (p < 0.05), and treatment satisfaction rates were significantly higher in the HIFU group (p < 0.05). Conclusion: Both HIFU and RFA are safe and effective for benign breast tumors.
Keywords: benign breast tumor, high-Intensity focused ultrasound ablation, radiofrequency ablation, clinical efficacy, multiple lesions
Benign breast tumors are common among women, predominantly affecting those aged 15–35 years. 1 Surgical excision remains the most effective and definitive clinical treatment. 2 However, traditional open excision carries risks of postoperative bleeding, wound infection, scarring, and breast deformity.3,4 In recent years, minimally invasive surgery has gained widespread adoption due to its advantages of precise targeting, reduced intraoperative bleeding, smaller incisions, and shorter operative times compared to open surgery. 5 Nevertheless, minimally invasive techniques can still lead to complications such as hematoma, breast dimpling, ductal injury, skin damage, and tumor residue. 6 Advances in imaging technologies like ultrasound have fostered the development of thermal ablation techniques—including High-Intensity Focused Ultrasound (HIFU), Radiofrequency Ablation (RFA), Microwave Ablation (MWA), and Laser Ablation (LAA)—showing significant promise in the local treatment of solid tumors. Guided by ultrasound or other imaging modalities, these techniques generate heat within the target area, inducing coagulative necrosis of the tumor tissue to achieve an effect analogous to surgical resection. 7
High-Intensity Focused Ultrasound ablation is a novel non-invasive targeted thermal ablation method for benign breast tumors. Its appeal stems from characteristics such as non-invasiveness, absence of bleeding, lack of surgical scars, and suitability for patients with recurrent tumors after previous surgery. 8 Its principle relies on the good penetrability and energy deposition properties of ultrasound waves in human tissue. Under ultrasound guidance, low-energy ultrasound waves generated by an external transducer are precisely focused through the skin, fat, and breast tissue onto the target. The combined effects of thermal energy, cavitation, mechanical stress, and sonochemistry induce coagulative necrosis within the target tissue. 9 The heat generated by HIFU raises the focal point temperature to 60–100 °C, causing irreversible cellular death and achieving tumor ablation. 10 Both HIFU and RFA offer distinct advantages over other surgical methods, especially for multiple benign tumors. 11 However, the relative merits and drawbacks of thermal ablation techniques like HIFU for benign breast tumors require further elucidation through comparative clinical studies, particularly head-to-head comparisons between ablation modalities. This study compares the clinical efficacy of HIFU and RFA to further investigate their advantages, disadvantages, and overall effectiveness.
Materials and Methods
Patient Data
This study is a retrospective study. Preoperative notification of the advantages and disadvantages of each surgical method, allowing patients to freely choose which surgical method to perform. Data from patients with benign breast tumors who underwent thermal ablation surgery at the Breast Diagnosis and Treatment Center of The First Affiliated Hospital of Gannan Medical University between February 2021 and May 2024 were collected. Inclusion Criteria: (1) Diagnosis of benign breast tumor （fibroadenoma）confirmed by breast ultrasound and/or pathological biopsy; (2) Age 18–60 years; (3) No cognitive or communication barriers; (4) Complete medical records with accessible data; (5) Tumor distance from nipple >0.5 cm; (6) Maximum tumor diameter measured by ultrasound or contrast-enhanced ultrasound (CEUS) between 0.5–3 cm; (7) For multiple lesions, all tumors must be ipsilateral and number less than 10. Exclusion Criteria: (1) Male patients; (2) Pregnant or lactating patients; (3) Pathological diagnosis of malignancy; (4) Abnormal coagulation function, liver/kidney function, cardiopulmonary function; acute infection; severe psychiatric disorders; (5) Skin ulceration over the breast; (6) Patients lost to follow-up. Patients were divided into the High-Intensity Focused Ultrasound ablation group (HIFU group) and the Radiofrequency Ablation group (RFA group) based on the treatment modality. Tumors were further stratified by diameter: ≤ 1 cm, 1 cm < diameter ≤2 cm, and 2 cm < diameter ≤3 cm. Patients with multiple lesions were also categorized separately (HIFU multiple lesions group vs RFA multiple lesions group). Comparisons were made regarding baseline characteristics, perioperative outcomes, efficacy, prognosis, complications, and satisfaction.The reporting of this study conforms to STROBE guidelines. 12
Surgical Methods
HIFU Group
Equipment: JC200 Focused Ultrasound Tumor Therapeutic System (Chongqing Haifu Medical Technology Co., Ltd), comprising a focused ultrasound transducer, ultrasound driving power supply, patient positioning device, and system software (Figure 1). Procedure: Local infiltration anesthesia with 2% lidocaine was administered. The patient was positioned prone on the treatment table, with the target breast immersed in a degassed water bath. The target tumor and adjacent structures were monitored via real-time ultrasound imaging. Pre-treatment planning and intraoperative scanning utilized the sagittal ultrasound mode, with a slice spacing of 3 mm. Spot scanning was used for energy delivery during HIFU. Treatment power started at 100 W and was gradually increased during the procedure, ranging from 100–300 W depending on the tumor location. The operator manually adjusted the focus while communicating with the patient regarding pain perception. Power and energy delivery were adjusted based on real-time ultrasound visualization of hyperechoic grayscale changes within the tumor or patient feedback. Ablation was stopped when the entire tumor area on ultrasound was covered by hypoechoic changes, appearing as a uniform hyperechoic zone around the tumor with no further expansion, indicating complete ablation. Post-HIFU, an ice pack was applied to the treated skin area for at least 30 min. Sulfur hexafluoride microbubble contrast agent was administered postoperatively, and ultrasound was used to assess tumor vascularity as a preliminary efficacy evaluation. For multiple tumors, patient positioning was adjusted individually for each tumor. As HIFU is a relatively new ablation technology without dedicated guidelines, the procedure followed the “Technical Management Specifications for Tumor Ablation Therapy (2017 Edition).”
Figure 1.
The Working Principle of HIFU.
RFA Group
Equipment: RFE-3SN17G × 250–30 multi-tine radiofrequency ablation electrode (Nanjing Anjun Medical Co., Ltd); RITA 1500× radiofrequency generator (AngioDynamics, USA), comprising a central trocar needle, peripheral electrode needles, guide needle, guide needle hub, sliding handle, rear handle, cable, and plug (Figure 2). Procedure: Local infiltration anesthesia with 2% lidocaine was administered. A 1-mm skin incision was made at the puncture site over the benign tumor. The RF ablation needle was inserted through the incision under ultrasound probe guidance. The needle tip was advanced percutaneously under real-time ultrasound visualization until positioned within the tumor. The trocar was withdrawn, deploying the multi-tined RF ablation electrode. Under continuous ultrasound guidance, the needle tip was centered within the tumor. Radiofrequency energy was then activated, gradually increasing to the target temperature (selected from different settings) within 2 min. Intraoperative ultrasound monitored the ablation zone, characterized by the disappearance of vaporization shadows and a change from hypoechoic to hyperechoic appearance. Ablation was stopped when the entire tumor area showed uniform hyperechoic changes with no further expansion, indicating completeness. For multiple tumors, separate needle insertions approximately 2 cm from each tumor were performed, with each lesion ablated individually. The procedure followed the “Chinese Expert Consensus on Radiofrequency or Microwave Ablation for Breast Fibroadenoma (2022 Edition).”
Figure 2.
The Working Principle and Competition Settings of RFA.
Outcome Measures
Preoperative Baseline Data
Included patient age, BMI, benign breast tumor diameter/volume, and proportion of tumors stratified by diameter (≤1 cm, 1 cm < diameter ≤2 cm, 2 cm < diameter ≤3 cm).
Perioperative Indicators
Included operative time, hospital stay, intraoperative and postoperative pain severity assessed using the Numerical Rating Scale (NRS) (Table 1), procedural success rate, proportion of patients with multiple lesions treated, and treatment energy dose (where applicable).
Table 1.
Numerical Rating Scale (NRS) for Pain.
| Score | Clinical Manifestation |
|---|---|
| 0 | No pain |
| 1–3 | Mild pain (tolerable) |
| 4–6 | Moderate pain (tolerable, affects sleep) |
| 7–10 | Severe pain (intolerable) |
Postoperative Indicators
Included benign breast tumor volume reduction rate at 3 months and 6 months postoperatively (calculated as: [(Initial Volume - Final Volume) / Initial Volume] × 100%), volume reduction rate for multiple lesions at 6 months, and volume reduction rate at 6 months stratified by tumor diameter. Pre- and postoperative tumor volumes were measured independently by three experienced ultrasonographers, and the average value was used. Breast ultrasound employed high-frequency probes (7.5-15 MHz).
Prognosis and Complications
Prognostic indicators included postoperative tumor volume changes, time to pain resolution, time to return to normal work, effective ablation rate at 3 months (defined as volume reduction ≥65%) and 6 months, effective ablation rate for multiple lesions at 6 months, and treatment satisfaction. Postoperative tumor outcomes were categorized as: Enlarged (volume increase >10%), Stable (volume change within ±10%), Reduced (volume decrease >10% but <65%), or Effectively Ablated (volume decrease ≥65%). Complications recorded included subcutaneous hematoma, wound infection, poor wound healing, breast deformity, skin burn, nausea, and pain. 13
Statistical Analysis
Statistical analysis was performed using SPSS 26.0 software. Normally distributed continuous data were expressed as mean ± standard deviation (x̄ ± SD) and compared using Student's t-test (two groups) or ANOVA (multiple groups). Non-normally distributed continuous data were expressed as median and interquartile range (M (P25, P75)) and compared using non-parametric tests (Mann-Whitney U or Kruskal-Wallis). Categorical data were expressed as rates or percentages and compared using Chi-square tests or Fisher's exact test. The significance level was set at α=0.05. A *p*-value <0.05 was considered statistically significant.
Results
Comparison of Baseline Characteristics
A total of 298 patients meeting the criteria for thermal ablation of benign breast tumors were included. Among them, 147 patients (231 tumors) underwent HIFU, and 151 patients (193 tumors) underwent RFA. Preoperative clinical baseline characteristics are shown in Table 2. There were no significant differences between the groups in age, BMI, tumor diameter, tumor volume, or the proportion of tumors within different diameter ranges (*p* > 0.05), confirming comparability. A significantly higher proportion of patients in the HIFU group (51 patients) had multiple lesions compared to the RFA group (31 patients, *p* = 0.0062).
Table 2.
Comparison of Baseline Characteristics Between Groups.
| Baseline Characteristic | HIFU Group (n = 147 pts / 231 tumors) | RFA Group (n = 151 pts / 193 tumors) | p-value |
|---|---|---|---|
| Age (years) | 33（24,41） | 33（26,40） | 0.597 |
| BMI (kg/m²) | 21.49 ± 2.78 | 21.54 ± 2.57 | 0.722 |
| Tumor Diameter (mm) | 11.9（10.0,14.0） | 12.0（9.6,14.8） | 0.559 |
| Tumor Volume (mm³) | 478.86（284.13,957.05） | 462.00（246.29,847.54） | 0.508 |
| Tumor Diameter Stratification | 0.026 | ||
| ≤1 cm | 96（41.6%） | 67（38.4%） | |
| >1 cm & ≤2 cm | 117（50.6%） | 113（54.2%） | |
| >2 cm & ≤3 cm | 18（7.8%） | 13（7.4%） | |
| Patients with Multiple Lesions | 51 | 31 | 0.0062 |
*Note: Data presented as Median (IQR) or Mean ± SD or n (%). Tumor diameter group percentages are based on total tumors per group (HIFU n = 231, RFA n = 193).*
Comparison of Intraoperative Outcomes
All procedures were technically successful (100% success rate), including 2 patients with large multiple tumors who underwent staged HIFU treatments successfully. Immediately post-HIFU, sulfur hexafluoride microbubble contrast was administered; ultrasound showed complete absence of blood flow signals within all treated tumors. The median operative time was significantly shorter in the HIFU group (17 min) compared to the RFA group (30 min, *p* < 0.05). The mean hospital stay was significantly longer in the HIFU group (1.32 days) compared to the RFA group (1.16 days, *p* < 0.05). The mean intraoperative/postoperative pain score (NRS) was significantly lower in the HIFU group (2.51) compared to the RFA group (2.94, *p* < 0.05) (Figure 3).
Figure 3.
Comparison of Intraoperative Outcomes (A. Operation Time (min), B. Hospital Stay (days), C. Pain NRS Score).
Comparison of Postoperative Ablation Efficacy
Volume Reduction Rate
The mean treatment energy dose in the HIFU group was 10821.6 ± 7303.4 Joules. Real-time calculation of energy dose was not feasible for RFA. At 3 months postoperatively, tumors in the RFA group showed variable trends (some shrinking, some enlarging), while most tumors in the HIFU group showed shrinkage (though some enlarged). By 6 months, most tumors in both groups showed volume reduction, with fewer enlarging; significantly more tumors in the HIFU group reached the effective ablation range (Figure 4).
Figure 4.
Volume Reduction Rates (A. RFA 3 m, B. HIFU 3 m, C. RFA 6 m, D. HIFU 6 m).
There was no significant difference in volume reduction rate at 3 months between groups (*p* > 0.05). However, at 6 months, the mean volume reduction rate was significantly higher in the HIFU group (79.42% ± 24.87%) compared to the RFA group (59.68% ± 57.09%, *p* < 0.05). For individual lesions within multiple tumors at 6 months, the mean reduction rate was significantly higher in the HIFU group (76.60% ± 25.84%) versus RFA (55.24% ± 51.32%, *p* < 0.05). Stratified by tumor diameter at 6 months: No significant difference for tumors ≤1 cm (*p* > 0.05). For tumors 1 cm < diameter ≤2 cm, the HIFU group had a significantly higher mean reduction rate (77.91% ± 26.36%) versus RFA (57.52% ± 64.01%, *p* < 0.05). For tumors 2 cm < diameter ≤3 cm, the HIFU group also showed a significantly higher mean reduction rate (82.37% ± 13.62%) versus RFA (71.86% ± 14.64%, *p* < 0.05). See Table 3.
Table 3.
Comparison of Intraoperative and Postoperative Recovery.
| Indicator | HIFU Group | RFA Group | p-value |
|---|---|---|---|
| Volume Reduction Rate at 3 months | 58.30% ± 27.09% | 38.95% ± 56.82% | 0.314 |
| Volume Reduction Rate at 6 months | 79.42% ± 24.87% | 59.68% ± 57.09% | 0.003 |
| Vol. Red. Rate per Lesion (Mult. Tumors) at 6m | 76.60% ± 25.84% | 55.24% ± 51.32% | 0.014 |
| Vol. Red. Rate at 6 m by Diameter | |||
| ≤ 1 cm | 82.13% ± 26.95% | 71.70% ± 40.65% | 0.344 |
| > 1 cm & ≤ 2 cm | 77.91% ± 26.36% | 57.52% ± 64.01% | 0.028 |
| > 2 cm & ≤ 3 cm | 82.37% ± 13.62% | 71.86% ± 14.64% | 0.045 |
Volume Changes
In both groups, the majority of benign breast tumors showed significant volume reduction over time post-treatment. Mean tumor volume in the HIFU group decreased from baseline to 306.41 mm³ at 3 months and 174.82 mm³ at 6 months. In the RFA group, mean volume decreased to 522.19 mm³ at 3 months and 304.73 mm³ at 6 months. The volume reduction was statistically significant over time within each group (*p* < 0.05). Volume trends are illustrated in Figure 5.
Figure 5.
Changes in Benign Breast Tumor Volume Over Time (HIFU vs RFA).
However, some tumors showed enlargement or stability postoperatively. HIFU group results at 3 months: Enlarged 13%, Stable 2%, Reduced 46%, Effectively Ablated 39%. At 6 months: Enlarged 2%, Stable 0%, Reduced 16%, Effectively Ablated 82% (Figure 4). RFA group at 3 months: Enlarged 11%, Stable 53%, Reduced 15%, Effectively Ablated 21%. At 6 months: Enlarged 8%, Stable 3%, Reduced 30%, Effectively Ablated 58% (Figure 6). Overall, the proportion of effectively ablated tumors increased over time in both groups.
Figure 6.
Postoperative Tumor Volume Outcome Categories (A. 3 m, B. 6 m).
Ultrasound Follow-up
Postoperative ultrasound follow-up confirmed significant shrinkage in some tumors from both groups compared to pre-operative size (Figure 7).
Figure 7.
Pre-Op and Post-Op Ultrasound (A. HIFU Pre, B. HIFU 6 m, C. RFA Pre, D. RFA 6 m). Arrows Indicate Tumor Location.
Effective Ablation Rate
Successful ablation was defined by contrast-enhanced ultrasound (CEUS) showing no perfusion within the tumor, confirming necrosis. The non-perfused volume ratio (NPVR) was calculated as (Non-perfused Volume / Baseline Tumor Volume) × 100%. At 3 months postoperatively, there was no significant difference in the effective ablation rate between HIFU and RFA groups (*p* > 0.05). At 6 months, the effective ablation rate was significantly higher in the HIFU group (188/228 tumors, 82.70%) compared to the RFA group (62/107 tumors, 57.90%, *p* < 0.05). Stratified by diameter at 6 months: No significant difference for tumors ≤1 cm (HIFU 78.26% vs RFA 62.17%, *p* > 0.05). For tumors 1 cm < diameter ≤2 cm, the HIFU group had a significantly higher rate (100/120 tumors, 83.33% vs RFA 41/65 tumors, 63.08%, *p* < 0.05). For tumors 2 cm < diameter ≤3 cm, no significant difference (HIFU 12/18, 66.67% vs RFA 8/13, 61.54%, *p* > 0.05). The effective ablation rate for multiple lesions at 6 months was significantly higher in the HIFU group (114/133 lesions, 86.3%) versus RFA (23/45 lesions, 52.4%, *p* < 0.05). Time to pain resolution and return to normal work was significantly shorter in the HIFU group (*p* < 0.05). See Table 4. In the follow-up of this study, no recurrence of lesions at the surgical site was found in both techniques.Both groups of patients did not show any recurrence of the original tumor, and some patients who still had incomplete absorption one year after surgery underwent a second surgery.
Table 4.
Comparison of Prognostic Outcomes.
| Indicator | HIFU Group | RFA Group | *p*-value |
|---|---|---|---|
| Effective Ablation Rate at 3 months | 44.10% | 45.10% | 0.894 |
| Effective Ablation Rate at 6 months | 82.70% | 57.90% | 0.000 |
| Eff. Abl. Rate for Multiple Lesions at 6m | 86.30% | 52.40% | 0.006 |
| Time to Pain Resol. & Return to Work (days) | 1.1 ± 0.4 | 2.1 ± 0.6 | 0.000 |
| Eff. Abl. Rate at 6 m by Diameter | |||
| ≤ 1 cm | 78.26% | 62.17% | 0.061 |
| > 1 cm & ≤ 2 cm | 83.33% | 63.08% | 0.002 |
| > 2 cm & ≤ 3 cm | 66.67% | 61.54% | 0.768 |
Note: Data presented as % or Mean ± SD.
Comparison of Complications
There was no significant difference in breast appearance between the two techniques. All complications according to CTCAE v5.0 were Grade 1; no Grade ≥2 complications occurred. The most common adverse event in both groups was localized stabbing or distending pain in the treatment area. In the HIFU group: 2 patients (1.4%) reported localized warmth at the site, resolving spontaneously with ice application; 1 patient (0.7%) experienced mild skin burns and edema near the puncture site (possibly due to large tumor size and proximity to skin, with air bubbles during local anesthesia), resolving with ice and recombinant bovine basic fibroblast growth factor gel. In the RFA group: 34 patients (22.52%) reported chest tightness after elastic bandage compression, relieved by loosening the bandage within 24 h; all RFA patients (100%) developed small scars due to the 1 mm incision; 5 patients (3.3%) developed minor subcutaneous hematomas (possibly related to proximity to vessels or inadequate hemostasis), resolving with compression; 3 patients (1.9%) experienced nausea intra/post-operatively (possibly related to lidocaine dose). No skin burns (RFA), infections, or breast deformities were observed. The overall complication profile differed significantly between groups (Fisher's exact test value: 177.97; *p* < 0.05). See Table 5.
Table 5.
Comparison of Postoperative Complications.
| Complication | HIFU Group (n = 147 pts) | RFA Group (n = 151 pts) |
|---|---|---|
| Localized Stabbing/Distending Pain | 145 (98.6%) | 151 (100%) |
| Incision/Surgical Scar | 0 (0%) | 151 (100%) |
| Subcutaneous Hematoma | 0 (0%) | 5 (3.3%) |
| Skin Burn | 3 (2.0%) | 0 (0%) |
| Chest Tightness | 0 (0%) | 34 (22.5%) |
| Nausea | 0 (0%) | 3 (1.9%) |
Comparison of Satisfaction
Patient satisfaction was assessed via questionnaire during follow-up. Among the patients followed (HIFU: 134, RFA: 131), overall satisfaction was high in both groups. However, the proportion of patients reporting satisfaction with the treatment was significantly higher in the HIFU group compared to the RFA group (*p* < 0.05). See Figure 8.
Figure 8.
Patient Satisfaction (HIFU vs RFA).
Discussion
Benign breast tumors are prevalent among women. Most exhibit a long, slow natural course, though some grow rapidly. Incidence appears to be rising, potentially linked to increased life stress and lifestyle changes. 14 Management options include observation and surgical intervention. While surgical excision is the mainstay, traditional open surgery is associated with significant glandular trauma, prolonged recovery, scarring, and bleeding risks, diminishing its appeal. Minimally invasive vacuum-assisted biopsy (VAB) reduces scarring but still carries risks of glandular damage, bleeding, dimpling, and residual tumor. 15 In contrast, HIFU directly destroys tumor tissue via focused ultrasound waves. The focal point can be scanned throughout the tumor's 3D volume until complete coverage is achieved, with a sharp demarcation between treated and untreated tissue and no damage beyond the focus. It offers advantages of non-invasiveness, good directionality, tissue penetration, focusability, real-time monitoring, and precise targeting. 16 RFA, another thermal ablation technique, offers benefits over open surgery like minimal invasiveness, rapid effect, and significant efficacy. RFA also induces complete coagulative necrosis but requires slow, controlled temperature rise to minimize central carbonization. 17 Our comparative study provides further insights into the relative merits of these two ablation techniques.
This study included 298 patients (147 HIFU, 151 RFA). Technical success was 100% in both groups. Tumor volumes decreased significantly over time in both groups at 3 and 6 months postoperatively. Critically, at 6 months, the HIFU group demonstrated a significantly higher mean volume reduction rate and a markedly higher effective ablation rate (82.7%) compared to RFA (57.9%, *p* < 0.05). This confirms that both HIFU and RFA are effective treatments, with efficacy increasing over time, and suggests HIFU may achieve effective ablation more rapidly.
In the treatment of benign breast tumors with multiple lesions, the average volume reduction rate in the HIFU group was 76.60%, which was higher than 55.24% in the RFA group. In the HIFU group, the average volume reduction rate of benign breast tumors with 1 cm ＜ diameter ≤ 2 cm was 78.48%, which was also much higher than that in the RFA group, and the difference was statistically significant; At the same time, the volume reduction rate of benign breast tumors with a diameter of 2 cm ＜ 3 cm at 6 months after operation was 82.37% in HIFU group, and the difference was statistically significant. In terms of the effective ablation rate of patients with multiple lesions, the HIFU group (average 86.3%) was also much higher than the RFA group (average 52.4%), and the difference was statistically significant (P < 0.05). This is because, first of all, HIFU treatment can rapidly increase the temperature of the target tissue area. During the treatment process, ultrasound real-time imaging can monitor the echo changes of the treatment area, accurately evaluate the target tissue and surrounding tissues, and reduce the absorption of the inactivated tissue by the body due to excessive ablation and carbonization in the tumor tissue 18 ; HIFU can achieve safe and effective ablation, which is not affected by the moving organs, while killing tumor cells, and does not affect the surrounding normal cells and vascular system. Its multi focus combination therapy can simultaneously treat multiple benign tumors distributed in four quadrants, or even multiple benign tumors in the same quadrant. It has the advantage of multi-point ablation, especially in large multiple benign breast tumors, it can improve the absorption rate of necrotic tumors after ablation and reduce the incidence of complications; At the same time, the therapeutic target can be scanned in motion along the three-dimensional shape of the benign tumor, covering the tumor in an all-round way, and the boundary between the therapeutic area and the non therapeutic area is clear until the tumor tissue is destroyed. 19 The ablation range is accurate, and the energy dose can also be accurately controlled. The average treatment dose in the HIFU group is 10821.6 ± 7303.4j. Second, radiofrequency ablation inserts the radiofrequency ablation electrode into the benign breast tumor tissue through percutaneous puncture, generating high-frequency AC current to radiate the energy in an oval way, especially the accurate evaluation of tumor ablation, the control of appropriate energy and treatment time, and the real-time monitoring of the ablation process, including the histopathological area of complete coagulation necrosis that cannot be accurately determined by ultrasound monitoring, the fuzzy edge of complete necrosis caused by the hyperecho of heated breast tissue, and the deeper area that cannot be monitored by ultrasound image shadow. 20 Based on this, it is impossible to accurately determine the necrotic range of the lesion during ablation and whether there is residual tumor. Especially in large benign tumors, it is impossible to accurately control the energy dose, which affects the absorption rate of necrotic tumor tissue. At the same time, it is impossible to further ablate the tumor with incomplete peripheral ablation. Whether it is to increase the release of energy or multi-point ablation, it will increase the risk of expanding the carbonized area of breast tissue. When the local tissue temperature rises to 100 °C, the tissue is prone to boiling, gasification or carbonization, and its resistance increases to limit the flow of RF current, reduce the heat transfer efficiency, resulting in the reduction of ablation range. 21 This experiment also further verified the results: in RFA group, some benign tumors had different degrees of volume expansion or stable trend at 3 months and 6 months after operation; For benign breast tumors with different sizes and diameters, especially those with diameters ranging from 1 to 2 cm, the average volume reduction rate of RFA group was 57.52%, which was lower than that of HIFU group (77.91%). At the same time, the effective ablation rate of 1 cm ＜ diameter ≤ 2 cm MRFA group was also lower than that of HIFU group; The size of nodules may affect the absorption effect of ablation focus after RFA; This is because radiofrequency ablation can not completely destroy the tissue 2.0 cm away from the center of the lesion. The breast tissue near the radiofrequency electrode is directly heated by the maximum current, and the tissue far away from the radiofrequency electrode is indirectly heated by heat conduction. The location of tumor lesions also affects the efficacy of RFA. When tumor lesions are close to large blood vessels, tumor cells cannot be completely removed due to blood cooling. 22 However, a small part of the tumor volume showed a trend of expansion. It was considered that the uneven radiation of radiofrequency ablation energy to the tumor tissue and surrounding normal tissue resulted in irregular absorption of ablation tissue and edema of normal tissue, and some were caused by excessive energy deposition and carbonization of normal tissue; It can be concluded that in the treatment of multiple and benign breast tumors with a diameter of 1∼2 cm, HIFU treatment is more advantageous and controllable, and the options are diverse. In this experiment, two patients with multiple lesions underwent secondary HIFU treatment after the interval cooling period, and the multiple lesions were effectively ablated.
In terms of operation time, the operation time of HIFU group is shorter than that of RFA group. For patients who can not tolerate long-term operation treatment, HIFU treatment takes a shorter time, which can reduce the generation of intraoperative anxiety and further reduce the occurrence of intraoperative complications, especially the occurrence of benign breast tumors is related to endocrine system estrogen (E), progesterone (P) disorders and even anxiety. 23 In terms of hospitalization time, the RFA group was shorter than the HIFU group. Considering that in the RFA group, some patients still required to perform breast tumor puncture and radiofrequency ablation at the same time after informing them of the risk of performing radiofrequency ablation treatment without reporting the pathological results of breast tumor puncture, and then formulated the corresponding treatment plan according to the pathological results of breast tumor puncture, which significantly reduced the hospitalization time. The single center prospective cohort study conducted by kovatcheva et al 24 also confirmed the efficacy of secondary hiuf in the treatment of breast fibroadenoma. On the basis of one HIFU treatment (group 1), some patients received secondary HIFU treatment (group 2) during the follow-up period. The volume of breast fibroadenoma in the two groups decreased during the postoperative follow-up, gradually absorbed as the follow-up time passed, and the secondary HIFU treatment had a more significant volume reduction effect. High intensity focused ultrasound ablation has the advantage of shorter operation time than radiofrequency ablation, but in terms of hospitalization time, we can further explore a treatment scheme suitable for multiple HIFU treatment of multiple and large-diameter benign breast tumors and further shorten the hospitalization time, which may be solved with the innovation of medical technology in the future.
In this experiment, the most common adverse reactions of the two groups were tingling or swelling pain in the treatment area. In terms of intraoperative and postoperative pain scores, the average values of the two groups were at a low level, and the average NRS of the HIFU group and RFA group were 2.51 and 2.94, respectively. The difference was statistically significant (p < 0.05). In HIFU group, 2 patients (1.4%) had burn sensation at the scar, which could be relieved by themselves after operation. HIFU has the advantages of no surgical scar and surgical incision in the treatment of benign breast tumor, but the treatment is affected by surgical scar, so the treatment of patients’ scar should be carried out carefully, as Zhang C et al 25 proposed in the experiment that ultrasonic beam can reach the target tissue through skin, adipose tissue and normal breast gland tissue. When the ultrasonic beam is at the junction of different tissues, the deposition of ultrasonic will be amplified. When the scar is in the acoustic channel through which the ultrasonic beam passes, the abnormal scar tissue and surrounding normal tissues will lead to the deposition of ultrasonic energy, which will cause thermal injury and skin scald during treatment. Another patient (0.7%) had skin scald for several times with mild edema. Considering the large size of the tumor and the close distance from the skin, after local anesthesia, there were bubbles at the skin puncture site, resulting in mild skin scald. It turned better after ice compress and drug conservative treatment. At present, in terms of reducing the risk of skin burns, for patients with multiple and large-diameter benign breast tumors, multiple HIFU treatments can be used to ensure the cooling interval and reduce energy deposition. At the same time, local anesthetics were injected into the subcutaneous space to increase the distance between the skin and the tumor. In RFA group, 34 patients (22.52%) developed chest tightness after compression bandage, and the elastic bandage could be slightly tightened 24 h after operation to relieve symptoms; In RFA group, the incision size was 1 mm, and small skin scars (100%) were inevitable after operation. Among them, 5 patients (3.3%) had mild subcutaneous hematoma. When considering the ablation of benign breast tumor tissue, it was close to the large blood vessels. Due to the effect of blood cooling, the tumor cells were not completely removed, and the vascular injury was not effectively stopped; Subcutaneous hematoma was slowly absorbed after 24 h of compression bandage; Another 3 patients (1.9%) developed nausea, which was caused by intraoperative injection of local anesthetic lidocaine; No discomfort such as skin scald, infection and breast deformation was found during the study.
At the same time, in the follow-up, the pain recovery and normal working time in the HIFU group were lower than those in the RFA group, and the difference was statistically significant (P < 0.05), which showed that HIFU treatment had faster recovery speed, less trauma to breast tissue, faster recovery of normal life and work after treatment, and improved the quality of life. At the same time, 126 patients (94%) of 134 patients in the HIFU group were satisfied with the operation and breast appearance, and some patients were considered to be general and a few were dissatisfied, which was much higher than that in the RFA group (76.6%), indicating that patients had a higher evaluation of HIFU in the treatment of benign breast tumors and were more inclined to choose high intensity focused ultrasound ablation.
Limitations
As a retrospective study, inherent limitations include potential for selection bias, subjective errors, and incomplete/inaccurate data. The single-center design limits generalizability.
Conclusion
The management of benign breast tumors remains a focus of clinical attention. Evolving from open surgery to minimally invasive techniques like VAB, thermal ablation (HIFU, RFA) now offers promising alternatives. HIFU, characterized by non-invasiveness (no scar, no bleeding), shorter procedure time, rapid recovery, fewer complications, tolerable pain, real-time monitoring, and treatment flexibility, demonstrates particular efficacy for multiple lesions and tumors 1–2 cm in diameter, alongside higher patient satisfaction. RFA offers a shorter hospital stay. Both HIFU and RFA are safe and effective treatments for benign breast tumors. Future directions include exploring combination therapies (ablation + drugs) and robotic guidance to further enhance outcomes.
Acknowledgements
Not applicable.
Footnotes
ORCID iD: Zhiyong Liu https://orcid.org/0000-0003-3277-7626
Ethics Approval: This study was approved by the Medical Ethics Committee of First Affiliated Hospital of Gannan Medical University (Approval No. GNYFY202101-07). Permission for publication was subsequently granted by the same committee (Approval No. LLsc-2024 No. 334).
Patient Consent Statement: The requirement for patient informed consent was waived due to the retrospective nature of the study.
Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: General Project (2024KFKT025), Open Research Program of the State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing.
Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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