Cryoablation-guided breast-conserving surgery: a single-center, retrospective study based on a propensity score-matched cohort

Introduction

According to the statistics in 2025, breast cancer represents approximately 32% of all newly diagnosed cancers in women (1). Breast-conserving surgery (BCS) has become the standard treatment for early-stage breast cancer (2,3), but its invasiveness may prolong treatment duration and increase the incidence of procedure-related adverse events (4). Moreover, some cosmetic outcomes, including scar formation and breast asymmetry, dissatisfy approximately 10% to 40% of patients (5). The goals of BCS involve the complete removal of tumor lesions, maximal preservation of breast shapes, and achievement of negative surgical margins (6). Surgical specimens after BCS display a positive margin rate of approximately 9.4% and a positive or close margin rate of approximately 17.8% (7). For patients with positive or close surgical margins after BCS, the probability of local and distant recurrences increases, which is associated with a higher mortality (7,8). Therefore, during BCS, surgeons should ensure negative margins and avoid close margins to improve patients’ prognoses (7,9).

No standards have been internationally recognized for real-time margin assessment during BCS. Current intraoperative assessment commonly relies on pathological analysis (e.g., frozen section analysis and imprint cytology), which can prolong surgical duration and have a limited implementation (10,11). Routine cavity shaves can reduce the incidence of positive margins (12), but may result in increased excision of breast volume (13). During intra-BCS exploration, most surgeons use the naked eye to differentiate tumor tissue from adjacent normal breast parenchyma, and then palpate to determine the extent of resection. In addition to palpation, small or non-palpable lesions should be localized before the start of BCS. Common localization methods include preoperative ultrasound marking and dye marking, both intending to facilitate lesion localization and margin determination (14,15). However, ultrasound marking depends on sonographic visibility and operators’ experience (14). In addition, the accuracy of dye marking may be compromised as the dye diffuses into the surrounding tissue, particularly when the time interval between localization and surgical initiation is prolonged (15). Therefore, the outcome of BCS is largely associated with the surgeon’s experience and other subjective factors.

In recent years, cryoablation has demonstrated a promising clinical efficacy in the treatment of small breast cancers (16), mainly through generating extreme cold temperatures (17). Cryoablation involves the insertion of a cryoprobe into the tumor under the guidance of imaging tools, such as ultrasound. Using cryogens, such as argon gas or liquid nitrogen, the cryoprobe generates an ice ball that covers the tumor and rapidly reduces the target tissue temperature to lethal levels (18). These low temperatures induce the formation of intracellular and extracellular ice crystals, leading to osmotic shifts and the collapse of cellular structures. Repeated freeze-thaw cycles damage tumor microvasculature, causing ischemia and enhanced tumor necrosis (17-19). Compared to other ablation techniques, cryoablation is more tolerable because of the analgesic effect of freezing in the treatment of small breast cancer (20). Additionally, cryoablation is highly compatible with ultrasound guidance, allowing smooth real-time monitoring of the treatment procedure (18,21).

At present, the indications for cryoablation in breast cancer remain relatively limited to a small subset of patients. As cryoablation has not yet become a standard alternative to surgery for patients with breast cancer, most patients still undergo surgery after cryoablation (20,22,23). However, few studies have examined the impact of cryoablation on subsequent BCS and sentinel lymph node biopsy (SLNB). In our previous studies, we have found that compared to non-ablated lesions, breast tumors become more palpable after cryoablation, with clearer intraoperative appearance and texture. Based on these observations, we hypothesized that cryoablation-treated breast tumors could be resected more accurately than untreated primary tumors during BCS.

In this retrospective study, we assessed whether preoperative cryoablation could improve the safety of surgical margins and accuracy of BCS for early-stage breast cancer, and influence the success rate of SLNB. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0027/rc).

Methods

Study design

A retrospective study was designed, in which clinical data were collected from all patients who underwent BCS in the Department of Breast Surgery at The First Affiliated Hospital with Nanjing Medical University between December 2024 and December 2025. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Committee of The First Affiliated Hospital with Nanjing Medical University (No. 2024-SR-725) and individual consent for this retrospective analysis was waived.

Inclusion criteria were as follows: (I) female patients aged between 18 and 70 years old; (II) preoperative imaging confirmed a single breast tumor lesion; (III) clinical assessment identified a tumor diameter of ≤3 cm; (IV) core needle biopsy (CNB) confirmed the breast cancer as invasive; (V) the patient received BCS. Exclusion criteria were as follows: (I) the patient had received systemic chemotherapy, targeted therapy, or local radiation therapy prior to surgery; (II) CNB revealed that the tumor was invasive carcinoma with extensive intraductal component (≥50%); (III) the tumor had invaded the skin or muscle; (IV) the tumor had invaded the nipple; (V) the tumor was pathologically defined as metaplastic carcinoma, inflammatory breast cancer, or concomitant sclerosing adenosis; (VI) the patient showed a poor overall condition or coagulation dysfunction.

Preoperative assessment

Before treatment, all patients were diagnosed with invasive early-stage breast cancer based on a multimodal diagnostic approach, including clinical examination, imaging evaluation, and pathological confirmation by CNB. Prior to BCS, biopsy samples were also subjected to immunohistochemical (IHC) staining to determine hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) expression. Post-operative adjuvant systemic therapy was recommended according to pathological stage and molecular subtype.

Cryoablation procedures

Before cryoablation, ultrasound skin marking was used to localize the target tumor. The three orthogonal diameters of the tumor were measured and recorded by ultrasound. Tumor images with the longest cross-section were obtained, with the longest axis and its perpendicular axis designated as the long axis and short axis, respectively, and the plane containing both axes was defined as the maximal plane. The corresponding skin projections and the extent of the tumor were marked. The puncture site of the cryoprobe was planned within the predetermined surgical incision. Povidone iodine disinfectant was used to routinely disinfect the skin around the puncture site, and after draping, local infiltration anesthesia was administered. The cryoablation device used in this study was the AH-22 system (Beijing Sunshine Yibang Medical Technology Co., Ltd., Beijing, China). The cryoprobe utilized was the K-13S (Beijing Sunshine Yibang Medical Technology Co., Ltd., Beijing, China).

Cryoablation employed a single-cryoprobe approach. First, the cryoprobe (K-13S) was connected to the AH-22 system, and its freezing and thawing effects were tested using sterile saline. After confirming that both the cryoprobe and the cryoablation system were functioning properly, the cryoprobe was inserted into the tumor through a pre-set puncture site. Under ultrasound guidance, the cryoprobe was adjusted to the position centered along both the long and short axes of the tumor. The tip of the cryoprobe was extended 1.0 cm beyond the tumor’s edge. The cryoablation protocol was set to 100% output power and individualized according to tumor diameter (Table 1). Then, the cryoprobe was fixed in position, while ultrasonography was used continuously to monitor echogenic changes in the mass and the expansion of the ice ball, ensuring that the ice ball completely covered the tumor and extended at least 1 cm beyond its boundary. Warm saline-soaked gauze or a sterile glove filled with warm saline was applied to the skin surrounding the treatment area to prevent frostbite.

BCS procedures

Approximately one week after cryoablation, BCS was performed on patients in the cryoablation group.

As controls, the patients in the surgery group underwent the same ultrasound skin marking procedures as those in the cryoablation group, and then underwent BCS directly. Neither group underwent preoperative wire localization or dye marking for tumor localization. The BCS procedures were the same in both groups. A radial or curved skin incision was made according to the localization of the tumor, followed by layer-by-layer dissection of the subcutaneous tissue. The tumor was localized by differentiating its color, texture, and morphology from normal tissues and by palpating its firm boundaries. After localization, the tumor was separated from the overlying tissue and exposed. The breast tissue was then dissected circumferentially along the tumor margin into the retromammary space, allowing the surgeon to mobilize the tumor manually and assess the extent of resection margins. The tumor was subsequently excised completely from the surrounding breast tissue. SLNB was performed in eligible patients in both groups. Systemic treatment was recommended based on established clinical guidelines.

Pathologic evaluation

After BCS, the resected specimens were promptly delivered to the pathology department for further processing. The volume of each specimen was measured, and its resected margins were inked by the pathologist. The specimen was serially sectioned at 5 mm intervals. Sufficient tissue samples were collected from the ablation zone and subjected to hematoxylin and eosin (H&E) staining, immunohistochemical staining, and nicotinamide-adenine dinucleotide (NADH) diaphorase staining. The viability of tumor cells after cryoablation was examined and documented under an optical microscope. Complete ablation was defined as the absence of viable tumor cells. A positive margin was defined as the presence of tumor cells at any site on the inked margin, whereas a negative margin was defined as the absence of tumor cells at all inked margins (9). Additionally, a close margin was defined as a distance of less than 1 mm between tumor cells and the inked margin, in the absence of tumor on ink (24). If the tumor was located 1 mm to 3 cm away from each inked margin, BCS was considered accurate (25).

Safety evaluation

Patients’ vital signs were continuously monitored throughout the cryoablation procedures. Treatment-related AEs, particularly skin-related AEs and pain, were recorded. The severity of AEs was evaluated using a five-level grading system, and that of pain using the numerical rating scale (NRS). Corresponding management measures for AEs were also documented.

Follow-up

All patients underwent a comprehensive breast physical examination immediately after cryoablation, three days post-cryoablation, and before BCS. Clinical features, including breast symmetry, scar visibility, lesion size, and lesion firmness, were compared before and after cryoablation. The two groups of patients were followed up and re-examined at the outpatient department at 1, 3, 6, 9 and 12 months after BCS. Follow-up assessments involved breast ultrasonography, documentation of subsequent adjuvant treatment plans, short- and long-term AEs and their management. Post-operative breast symmetry and cosmetic outcomes were assessed using a four-point scale (excellent, good, fair, and poor) based on the Harvard Cosmesis Criteria (26,27), with standardized frontal photographs compared with those of the contralateral breast. An excellent result indicated a nearly identical appearance; a good result indicated a slight difference; a fair result indicated an obvious difference without severe distortion; and a poor result indicated a marked breast distortion. The subjective evaluation was conducted by an expert panel from our department. The post-operative length of stay (LOS) was calculated as the time interval between the date of BCS and the discharge date.

Statistical analysis

Numerical data were summarized using descriptive statistics, including median, percentile, range, mean, and standard deviation. To reduce potential bias and confounding due to baseline clinical differences between both groups, propensity score matching (PSM) in a 1:2 ratio was performed for variables including age, tumor histology, tumor size, molecular subtype, and clinical axillary lymph node status. Normally distributed continuous variables were compared using Student’s t-test. The Wilcoxon rank-sum test was used for continuous variables that were not normally distributed. The chi-square test or Fisher’s exact test was used to compare categorical variables. All statistical analyses were performed using software PASS 2025 and IBM SPSS Statistics version 29.0. A two-sided P<0.05 was considered statistically significant.

Results

Baseline characteristics

This retrospective study analyzed the data from 269 patients who underwent BCS at our center between December 2024 and December 2025. Screened by inclusion and exclusion criteria, 207 patients were eligible. Of them, 41 patients underwent ultrasound-guided cryoablation followed by BCS approximately 1 week later, whereas the remaining 166 patients underwent direct BCS after the completion of relevant examinations and preoperative ultrasound skin marking. Figure 1 illustrates the flowchart for patient selection. Before treatment, all patients were diagnosed with invasive early-stage breast cancer according to a combination of clinical, imaging, and pathological (core needle biopsy) data. Figure 2 shows the pre-ablation ultrasound, mammography, and magnetic resonance imaging (MRI) findings of a representative patient with early-stage breast cancer. The baseline clinical characteristics of patients who underwent preoperative cryoablation are presented in Table 2. After PSM, a matched cohort was formed, consisting of 37 patients in the cryoablation group and 74 patients in the surgery group. The baseline characteristics of the two groups are summarized in Table 3. In this matched cohort, no statistically significant differences were observed in age, tumor size, clinical axillary lymph node status, tumor histology or molecular subtype.

Figure 1 Study flowchart.

Figure 2 Pre-ablation breast imaging findings in a 36-year-old woman with early-stage breast cancer. (A) The MLO mammographic view demonstrated an irregular mass (arrow) measuring approximately 1.7 cm in the upper outer quadrant of the right breast. The lesion was classified as BI-RADS category 4B. (B) Ultrasound revealed a hypoechoic mass (arrow) in the right breast, located deep to the glandular margin at the 10 o’clock position, measuring approximately 1.7 cm and classified as BI-RADS 4B. (C) Magnetic resonance imaging revealed an enhancing mass (arrow) measuring approximately 1.7 cm in the upper outer quadrant of the right breast, classified as BI-RADS 4C. BI-RADS, Breast Imaging Reporting and Data System; MLO, mediolateral oblique.

Preoperative cryoablation-guided BCS

In the cryoablation group, a total of 37 breast specimens were harvested after resection, and none exhibited a positive margin, regardless of whether complete ablation was achieved. The rate of accurate surgery in the cryoablation group was 83.78% (31/37), with a mean resected specimen volume of 79.32±46.93 cm³. Among the 6 patients with inaccurate surgery in this group, pathological examination showed that 2 cases (2/37, 5.41%) had a close margin, and 4 cases (4/37, 10.81%) had a largest margin >3 cm. The rate of accurate surgery in the surgery group was 59.46% (44/74), with a mean resected specimen volume of 78.77±41.45 cm³. Among the 30 patients with inaccurate surgery in this group, pathological examination showed that 6 cases (6/74, 8.11%) had a positive margin, 18 cases (18/74, 24.32%) had a close margin, and 8 cases (8/74, 10.81%) had a largest margin >3 cm. It is worth noting that 2 cases had both a close margin and a largest margin >3 cm. In contrast, the cryoablation group exhibited a significantly lower rate of positive or close margin (5.41% vs. 32.43%, P=0.002) and a higher rate of accurate surgery (83.78% vs. 59.46%, P=0.01) (Table 4). Additionally, the mean operative time for BCS in the cryoablation group was approximately 10 minutes shorter (76.65±8.17 vs. 86.50±16.29 min, P<0.001). No statistically significant between-group differences were observed in the rate of largest margin >3 cm, pathological tumor size, pathologic axillary lymph node status, resected specimen volume or estimated blood loss (all P>0.05).

Effect of cryoablation

The effect of cryoablation in the treatment of breast cancer was assessed in 37 patients. Of them, 2 patients had tumors of ≤1 cm, 11 patients of >1 and ≤2 cm, and 24 patients of >2 cm on ultrasound. In the initial stage of cryoablation, the temperature at the cryoprobe tip could drop below −160 ℃ within 60 seconds. The AH-22 system provided real-time monitoring of this temperature. Throughout the treatment, the target tumor region showed typical ultrasound appearances (Figure 3A-3D). The ice ball expanded outward from the cryoprobe, gradually covering and extending beyond the entire hypoechoic tumor area. On the tumor’s long-axis ultrasound image, a crescent-shaped hyperechoic margin was observed, along with a uniform elliptical hypoechoic area caused by ultrasound reflection from the ice ball and an accompanying posterior acoustic shadow. The tumor’s short-axis ultrasound image showed an arched hyperechoic edge, with a uniform hypoechoic circular region inside and an acoustic shadow posterior. Ultrasound-guided cryoablation was successfully performed in all 37 patients under local anesthesia, with a mean duration of 38.11±9.53 min. Under ultrasound guidance, all tumors were completely covered by ice balls formed during cryoablation.

Figure 3 Ultrasound-guided cryoablation images in a 36-year-old woman with early-stage breast cancer; the patient is the same individual shown in Figure 2. (A) Long-axis ultrasound imaging confirmed that the cryoprobe’s distal tip (arrow) was 1 cm beyond the mass, and the cryoprobe was well positioned. (B) The cryoprobe (arrow) was positioned at the center of the tumor’s short axis before cryoablation. (C) During cryoablation, long-axis ultrasound imaging demonstrated that as the ice ball rapidly expanded, its hyperechoic margin gradually covered the tumor boundary, while the cryoprobe (arrow) remained visible. (D) During cryoablation, short-axis ultrasound imaging showed that the ice ball margin covered and extended beyond the tumor boundary.

In routine post-BCS pathological examination, all specimens resected from the cryoablation group exhibited three generally distinct zones. The central ablation zone appeared as a dark red necrotic region, indicating that severe cryogenic damage had caused hemorrhagic necrosis. The peripheral ablation zone presented as a light red ring-shaped area approximately 0.5–1 cm thick. All tumors in the cryoablation group were confined within the ablation zone. The outermost zone consisted of normal adipose and glandular tissue. The boundaries between the central ablation zone, peripheral ablation zone, and normal breast tissue could be clearly distinguished by the naked eye (Figure 4A,4B). Following cryoablation, the tumor tissue became firmer and showed a tactile profile clearly distinct from that of the surrounding tissue. A significant difference in the overall tumor morphology was observed between both groups (Figures 4,5). H&E staining, IHC staining and NADH-diaphorase staining revealed complete ablation in 35 of the 37 cases in the cryoablation group, with no viable tumor cells detected in the central ablation zone, peripheral ablation zone, or adjacent tissue beyond the ablation zone (Figure 6A,6B). The complete ablation rate of cryoablation was 94.59% [35/37; 95% confidence interval (CI): 82.3–98.5%]. Post-operative pathological specimens from all patients were visually inspected, showing that the cryoprobe puncture was inaccurate in 2 patients, and their tumors were incompletely ablated. Despite incomplete ablation, both cases also underwent accurate surgery, with resected specimen volumes of 87.50 cm³ (slightly larger than the average) and 51.75 cm³, respectively. They showed no increase in complications or prolongation of LOS either.

Figure 4 Gross appearance of pathological specimens from a 35-year-old patient in the cryoablation group after breast-conserving surgery. (A) Macroscopic view of multiple sections from the breast-conserving specimen. (B) Single cross-sectional view of the specimen showed dark-red hemorrhagic necrosis in the central ablation zone (black arrows), a light-red peripheral ablation zone (red arrows), and normal breast tissue at the outermost margin (yellow arrows).

Figure 5 Gross appearance of the pathological specimens from a 40-year-old patient in the surgery group after breast-conserving surgery. The tumor exhibited irregular infiltrative growth (arrows), with a grayish-white color and a nodular appearance on the section. The boundary was blurry between the tumor and the surrounding tissue.

Figure 6 Hematoxylin and eosin staining of tumor tissue from a 57-year-old patient with breast cancer after cryoablation. (A) At 100× magnification, the tumor tissue in the central ablation zone exhibited transparent necrosis with areas of hemorrhage. No intact tumor cell structures were observed. However, residual nuclear debris from disrupted tumor cells remained visible (black arrow). (B) At 100× magnification, no viable tumor cells were detected in the peripheral ablation zone (red arrow) or the adjacent normal glandular tissue (yellow arrow).

Cryoablation-related AEs

All 37 patients in the cryoablation group tolerated cryoablation, with 8 patients (8/37, 21.62%) reporting mild pain, 2 patients (2/37, 5.41%) moderate pain, and 27 patients (27/37, 72.97%) no pain. Pain decreased gradually and disappeared within 24 hours following cryoablation. Additionally, two patients (2/37, 5.41%) experienced mild skin-related AEs, including one with mild skin frostbite (approximately 1 cm in diameter) and one with local subcutaneous hematoma in the nipple-areola region (Table 5). Skin frostbite was managed with regular dressing changes to cleanse the wound, followed by the application of non-adhesive sterile dressings to keep the wound dry. Both mild skin frostbite and subcutaneous hematoma resolved within 7 days. No patient experienced persistent AEs or other cryoablation-related complications, such as incision infection or pectoral muscle frostbite. No surgeries were delayed because of cryoablation-related complications.

SLNB after cryoablation

Of the 37 patients receiving cryoablation, 36 (36/37, 97.30%) underwent SLNB. Routine pathological examination confirmed positive sentinel lymph nodes (SLNs) in 11 patients (11/36, 30.56%) (Table 4). The success rate of SLNB was 100% (36/36) in this group, with SLNs successfully identified during the surgery in all patients. In the cryoablation group, the median number of detected SLNs was 3 (range: 1–5). In the surgery group, 62 patients (62/74, 83.78%) underwent SLNB, and routine pathological examination confirmed positive SLNs in 10 patients (10/62, 16.13%) (Table 4). The success rate of SLNB was 100% (62/62) in the surgery group, with a median of 2 SLNs detected (range: 1–4). No statistically significant between-group difference was observed in pathologic SLN status (P>0.05). The success rate of SLNB was the same in both groups.

Follow-up outcomes

The mean post-operative LOS in the cryoablation group was 1.59 days, approximately 1 day shorter compared to the 2.62 days in the surgery group (P<0.001). The median follow-up time in the cryoablation group was 9 months (range: 1–12 months), with 9 patients followed up for 12 months. The median follow-up time in the surgery group was 6 months (range: 1–12 months), with 15 patients followed up for 12 months. During the follow-up, all patients in both groups survived, with no observed local or systemic tumor recurrence. Two patients in the surgery group developed incision infections during the follow-up, whereas no other AEs were observed in either group. Cosmetic outcomes were rated as excellent or good in over 90% of patients in each group. No statistically significant differences were found between the two groups regarding post-operative adjuvant therapy regimens, incidence of AEs, or post-operative cosmetic outcomes (all P>0.05).

Discussion

Cryoablation, a minimally invasive ablation therapy, has been proven effective and safe to treat benign breast fibroadenomas (28,29) and is considered as a potential alternative to surgery. However, it remains in the early stages of clinical research for the treatment of breast cancer. Most previous clinical studies have been limited to invasive carcinomas with a tumor diameter of ≤2 cm and favorable molecular subtypes (30-33). In young or high-risk patients with breast cancer, current evidence remains insufficient to support the omission of surgery after cryoablation. In our previous studies, we have found that the intraoperative appearance and texture of breast tumors can be more clearly defined after cryoablation than those of non-ablated lesions. We hypothesized that cryoablation might facilitate the accurate resection of breast tumors.

A positive resection margin after BCS typically necessitates secondary resection to achieve marginal negativity (34,35). However, secondary resection can pose larger physical, mental and economic burdens on patients, and excessive removal of normal tissue potentially impairs breast appearance and quality of life (36,37). Meta-analytic evidence links margin involvement (and in some analyses, close margins) with inferior oncologic outcomes, underscoring the importance of thoroughly clearing margins at the first operation (7). Therefore, precise intraoperative identification of positive or close margins is needed to improve surgical outcomes.

In this single-center retrospective study, we evaluated whether preoperative cryoablation could assist in BCS without compromising standard oncologic clinical pathways. We found that cryoablation-guided BCS was technically feasible and statistically associated with higher margin quality and operative efficiency, without adversely affecting SLNB identification. A key interpretation of these findings is that cryoablation produces an ablation zone that enhances palpability and conspicuity, thereby improving the accuracy of intraoperative tumor localization. Mechanistically, the freeze-thaw-freeze cycle directly induces cellular lethality and microcirculatory failure, yielding a necrotic zone within the targeted tissue (38,39). After cryoablation, the tumor area appeared dark red with a firm texture and a distinct boundary from the surrounding normal breast tissue, providing clear landmarks for intraoperative exploration and tumor removal during BCS. No positive margin was found in breast specimens from patients in the cryoablation group, regardless of whether complete ablation was achieved. This may be explained by the fact that, although complete ablation was not achieved in two patients owing to inaccurate cryoprobe placement, the tumors remained within the ablation zone and this had a minimal impact on intraoperative tumor identification and localization. Notably, the cryoablation group showed a lower rate of positive or close margin and a higher rate of accurate resection. No significant differences were observed between the two groups in resected specimen volume, estimated blood loss, or post-operative cosmetic outcomes. We speculated that precise cryoablation, with minimal damage to surrounding normal breast tissue, may contribute to these superiorities. Additionally, the mean duration of BCS in cryoablation-pretreated patients was approximately 10 minutes shorter than that in non-ablated patients, which may be attributed to clearer tumor delineation after cryoablation, thereby facilitating BCS procedures. The mean post-operative LOS in the cryoablation group was approximately 1 day shorter, possibly because cryoablation did not result in complications that prolonged hospitalization.

Compared with the study by Tafra et al. (40), ours expanded the potential roles of cryoablation in BCS. Tafra et al. compared the beneficial effects of cryoablation-assisted localization and needle-wire localization in BCS, finding no significant difference in the positive margin rate between the two methods; however, the volume of resected tissue was significantly smaller in the cryoablation-assisted localization group than in the needle-wire localization group. In contrast, our findings suggested that beyond the assistance in tumor localization, preoperative cryoablation also eased intraoperative tumor identification and allowed more precise excision by creating a firmer and clearer lesion. In our study, given that the patients in the surgery group only underwent ultrasound-guided skin marking before BCS, our findings suggested that cryoablation may offer superior guidance to ultrasound-guided skin marking in BCS. Compared with ultrasound skin marking, cryoablation is disadvantageous in terms of treatment time, cost, and equipment requirements. Nevertheless, it remains a valuable adjunct, rather than an essential technique, for precise BCS. Cryoablation-guided BCS should be used as a complement to current strategies, such as cavity shaving. Notably, a meta-analysis shows that conventional margin assessment tools vary widely in diagnostic accuracy and practicality (10), while technique-driven approaches (e.g., cavity shaving) can reduce positive margins, but may require additional tissue removal (12,13). The impact of cryoablation-guided BCS on the performance and applicability of these techniques also requires further investigation.

The present study included 37 early-stage breast cancer patients with tumor diameters ≤3 cm and multiple molecular subtypes, thus expanding the indications of cryoablation summarized in previous research. In terms of safety, most patients experienced only mild or no pain during treatment with only local anesthesia, and the mean duration of cryoablation was shorter than 50 minutes. Skin-related AEs were rare, with only two patients (5.41%) experiencing mild events. This study did not observe any grade 3 or higher AEs associated with cryoablation. These data suggested that cryoablation could achieve good results in ablating unifocal invasive breast cancer with a diameter of ≤3 cm, with a complete ablation rate exceeding 90%. Therefore, cryoablation is both safe and effective for treating early-stage breast cancer.

SLNB is a standard surgical technique used to evaluate lymph node status in patients with early-stage breast cancer who present with clinically negative lymph nodes (41,42). It has been suspected that cryoablation might interfere with SLN detection (43). In our study, however, the success rate of SLNB in the cryoablation group was 100% (36/36), identical to that in the surgery group (100%, 62/62). No statistically significant between-group differences were observed in pathologic SLN status (P>0.05). These results suggest that preoperative cryoablation did not adversely impact the success rate of subsequent SLNB, and could be performed as an adjunct compatible with BCS.

In addition, cryoablation has been linked to immune cell recruitment and abscopal effects, supporting the hypothesis that cryoablation could induce systemic antitumor immune responses against breast tumors (44,45). Moreover, cryoablation may augment the responses to systemic immunotherapy (46). Cryoablation may not only guide BCS but also modulate the breast cancer immune microenvironment, warranting further evaluation in future clinical trials. Notably, no consensus exists on the clarity of tumor margins following cryoablation. Cryoablation-related factors, including ablation duration, the interval between cryoablation and surgery, and peri-ablation bleeding, may also influence the operator’s assessment of the ablation boundary. Future studies should incorporate elastography scores to enable a more objective evaluation of post-treatment changes in tumor margins and tissue stiffness.

This study has several limitations. First, its retrospective, single-center design may have introduced selection and information bias. Although PSM helped balance baseline characteristics of the two groups, body mass index (BMI) and other factors relevant to cosmetic outcomes, such as breast volume and breast density, were not included and matched, leaving residual confounding and selection bias. Larger, prospective, multicenter randomized controlled trials are needed in the future to validate the role and mechanism of cryoablation in guiding BCS. Second, although the matched sample size was sufficient to detect large differences in the pathological results of specimen margins, it provided limited statistical power for evaluating rarer events and subgroup analyses (e.g., molecular subtype-specific effects). Third, follow-up duration may be inadequate to fully assess long-term local recurrence and survival, particularly in patients with late recurrence risk. Longer follow-up periods are needed to evaluate the impact of cryoablation-guided surgery.

Conclusions

In conclusion, this retrospective study suggests that cryoablation-guided BCS is feasible and safe for early-stage breast cancer. Compared with standard BCS, cryoablation-guided BCS may enable more accurate resection and is also associated with a lower positive or close margin rate, shorter surgical duration and post-operative LOS. Moreover, cryoablation does not negatively affect the success rate of subsequent SLNB.

Acknowledgments

The authors would like to thank all the patients and researchers for their valuable help.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0027/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0027/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0027/prf

Funding: This study was supported by the National Natural Science Foundation of China (No. 82172683).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0027/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved bythe Institutional Ethics Committee of The First Affiliated Hospital with Nanjing Medical University (No. 2024-SR-725)and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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