Post-treatment patient satisfaction in early-stage breast cancer: comparison of cryoablation versus breast conservation therapy using BREAST-Q

Introduction

Over two million women worldwide, are diagnosed with breast cancer annually (1). However, treatment advances have led to increasing survival rates in many countries, including Japan (2). Various multidisciplinary oncology groups have recommended surgical de-escalation. De-escalation, particularly in the context of early breast cancer, involves a shift from radical surgery to breast conservation, favoring less-intensive surgical interventions. Currently, local treatments for breast cancer are trending towards minimally invasive procedures without compromising curative intent. This shift is largely due to early detection, which is facilitated by widespread breast cancer diagnosis, screening efforts, and advances in radiation therapy and systemic treatments (3,4). Currently, breast-conserving therapy (BCT) represents approximately 60% of all surgical treatments in Japan (5), and nonsurgical, minimally invasive therapies, such as radiofrequency ablation therapy (6) and cryotherapy (7), have emerged as novel treatment options.

Cryoablation has emerged as an established minimally invasive alternative to partial resection for early-stage breast cancer (8). However, few studies have compared patient satisfaction and health-related quality of life (HRQOL) (9) outcomes between cryoablation and BCT (10,11). Assessing these outcomes is crucial, as they provide essential information to help patients make informed treatment decisions. Therefore, evaluating and comparing these two treatment modalities in terms of patient satisfaction and HRQOL is of clinical importance.

Cryoablation, which induces target tissue necrosis through freeze-thaw cycles, is a short, safe, and effective outpatient procedure performed under local anesthesia for benign and malignant tumors of various organs, particularly in patients with early-stage breast cancer (8). The treatment of breast cancer has shifted from radical mastectomy to simple mastectomy, breast-conserving surgery, and recently, minimally invasive techniques, including radiofrequency ablation and cryoablation. The ICE3 clinical trials have shown that cryoablation without tumor resection for early-stage, low-risk, hormone receptor-positive breast cancer is a safe alternative to surgery (8).

Evaluation of emerging de-escalation therapies in breast cancer treatment encompass various aspects including effectiveness, HRQOL, patient satisfaction and cosmetic outcomes, alongside oncologic control (12,13). Specific HRQOL and patient satisfaction outcomes relevant to treatment decisions typically include Satisfaction with Breast cosmetic outcomes and QOL across the spectrum of physical, psychosocial, and sexual well-being. One of the most widely used tools to assess patient HRQOL and satisfaction internationally is the BREAST-Q, a rigorously developed patient-reported outcome measure used in cosmetic and reconstructive breast surgery and clinical practice (14-18). The prospective collection of center-specific data for different types of breast surgery is necessary for planning patient-centered and evidence-based care (18).

Previous study on BCT have shown that patient satisfaction measured by the BREAST-Q is influenced by factors such as body mass index (BMI) at the time of surgery, changes in BMI post-surgery, extent of axillary surgery, lymph node status, tumor size, specimen weight, and delayed wound healing (>30 days) (3).

Cryoablation has been conducted in a limited number of hospitals; therefore, research on patient satisfaction using the BREAST-Q remains scarce, especially among patients who have undergone minimally invasive percutaneous cryoablation treatment for breast cancer. Although BREAST-Q results have been documented for Western populations for a short post-treatment period, there is a paucity of BREAST-Q studies focusing on Asian patients with small breast size and a long post-treatment period.

In this study, we aimed to evaluate the post-operative HRQOL and patient satisfaction with cryoablation versus BCT in patients with early-stage breast cancer (Stage 0–1) using the BREAST-Q. This study will provide evidence to inform decision making for treatment choices in patients with early-stage breast cancer. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-24-394/rc).

Methods

Study design

This study was a prospective observational comparative study. A cross-sectional survey was conducted to retrospectively gather clinical information and establish a breast cancer patient cohort to assess post-operative patient satisfaction following cryotherapy versus BCT.

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol was approved by the Kameda Medical Center Clinical Research Review Committee (No. 21-036) and met the guidelines of the responsible governmental agency. Informed consent was obtained in the form of opt-out on the web-site.

Study population

At Kameda Medical Center, cryoablation has been performed on patients with early breast cancer since 2006. This study included patients with stage 0 and I breast cancer who underwent cryoablation or BCT at the hospital between April 1, 2022, and June 30, 2022. Patients who underwent axillary dissection, those with a tumor diameter >15 mm, those with bilateral breast cancer, and those who did not receive radiation therapy were excluded. As this study was an observational comparative study, the sample size was determined based on the available patient pool during the study period.

Outcomes

Post-operative patient satisfaction was assessed using the BREAST-Q questionnaire which comprises ten distinct components including Psychosocial Well-being, Sexual Well-being, Satisfaction with Breasts, Physical Well-being related to the chest area, Satisfaction with Information provided by breast surgeons, Satisfaction with Information given by radiation oncologists, Satisfaction with Surgeons, Satisfaction with Medical Teams, Satisfaction with Office Staff, and Adverse Effects of Radiation. With the exception of Adverse Effects of Radiation, each component was scored on a standardized scale of 0–100, with 100 indicating the highest patient satisfaction. No standardized scores were calculated for the Adverse Effects of Radiation, and patient satisfaction was indicated on a 1–3 Likert scale (1, not at all; 2, a little; 3, a lot). Similar to previous studies (12,19), the Satisfaction with Breasts component served as the primary endpoint in this study, while the other components were considered as secondary endpoints.

The survey was administered using the BREAST-Q [Version 2.0^©, Breast Conserving Therapy Module, Pre- and Post-operative Scales, Japanese (JP) Version] (20). The validity of the BREAST-Q in assessing HRQOL and patient satisfaction has been demonstrated in numerous studies (2,12,19). Outpatient staff distributed the survey to patients during routine clinic visits, and responses were collected on-site. Patient responses were kept confidential and were not disclosed to the treating physician.

Other variables

Additional patient characteristics obtained from electronic medical records included age; length of follow-up between surgery and survey; BMI at treatment day; tumor diameter; breast cancer pathology by biopsy [invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), invasive lobular carcinoma (ILC), special types]; breast cancer subtype by biopsy [luminal (PR-positive and/or ER-positive, HER2-negative), pure HER2 (-negative, ER-negative, HER2-positive), triple negative (TN)]; cancer stage (0, 1); tumor removal volume for BCT; adjuvant therapy (chemotherapy, endocrine, or radiation therapy).

Procedures

A biopsy was performed on all patients, and if invasive cancer was detected by pathology, a sentinel lymph node biopsy was conducted. Patients were divided into two groups according to the surgical procedure employed (cryoablation or BCT).

Cryoablation procedure

Cryoablation is a minimally invasive cancer treatment that utilizes extremely low temperatures to freeze and eliminate malignant cells. Cryoablation was performed at the hospital by a breast cancer surgeon with 40 years’ experience. The IceCure ProSense^TM cryoablation system (IceCure-Medical Ltd., Caesarea, Israel; Figure 1A) and a diameter needle known as a cryoprobe (10 G, 3.4 mm) were used for all cryoablation procedures. The ProSense^TM system maintained a cooling-center temperature of −170 °C at the cryoprobe tip (Figure 1B). The procedure was performed under ultrasound (US) guidance, with clear visualization of the tumor, cryoprobe position, and ice ball (Figure 2). Cryoablation was performed under local anesthesia according to standard day surgery protocols, with one freeze-thaw-freeze cycle of approximately 40 min and sufficient margin for the tumor.

Figure 1 Cryoablation system. (A) The ProSense^TM system used in this study. (B) The cryoprobe used in this study. The red circle shows the ice-covered tip of the cryoprobe. The temperature at the center is maintained at −170 °C.

Figure 2 Ultrasound imaging findings in a patient. (A) Cryoablation image. (B) Ultrasound image before cryoprobe insertion. A tumor measuring 8.0 mm × 9.0 mm is indicated by the white arrow. (C,D) Ultrasound image before and after cryoprobe freezing: (C) at the start of freezing; (D) at the end of freezing; the frozen area (“no-echo” area) was enlarged from C to D.

BCT procedure

Surgical resection was performed by a trained and experienced breast cancer surgeon according to standard protocols (21-24). The procedure was performed under general anesthesia and lasted for approximately 120 min.

Statistical analysis

Descriptive statistics were obtained for the demographic and clinical characteristics of patients in both the BCT and cryoablation groups. Between-group differences were assessed using the t-test for continuous variables and the χ² test for categorical variables.

Propensity score matching was used to adjust for patient background imbalances between the groups. A logistic model was used to calculate the propensity scores. In the model, exposure status (BCT or cryotherapy) was the dependent variable and potentially confounding variables (age at treatment, BMI, and length of follow-up period between surgery and survey) were used as explanatory variables. Matching was performed on a 1:1 basis using the nearest-neighbor method. The caliper was set at 10% of the standard deviation of the propensity score. The balance between groups for each variable before and after matching was evaluated by calculating the standardized mean difference (SMD). Following previous research, we judged that a variable was balanced when the SMD was less than 0.1 (25).

The t-test was used to compare cosmetic outcomes between groups, and the chi-square test was used to compare response rates. Statistical significance was defined as a two-sided P value of <0.05.

Results

A total of 147 Asian female patients underwent either cryoablation (n=42) or BCT (n=105) for breast cancer and attended outpatient visits between April 1 and June 30, 2022. Among these patients, 112 were diagnosed with stage 0 or 1 disease. Of the 112 patients, 36 were excluded, while 76 patients (35 with cryoablation and 41 with BCT) were included in the analysis (Figure 3).

Figure 3 Patient flowchart.

Table 1 shows the demographic information of patients in both groups. The observation period (1,527.74 vs. 1,458.95 days, P=0.80), patients’ age (60.31 vs. 56.9 years, P=0.19) and BMI over 25 kg/m² (11 participants vs. 8 participants, P=0.35) were not significantly different between the cryoablation and the BCT groups, respectively. All patients underwent post-operative radiation therapy after breast conservation or cryoablation therapy. Approximately one-quarter of the patients who underwent BCT also received post-operative chemotherapy, while none of the patients who underwent cryoablation received post-operative chemotherapy (26.8% vs. 0%, P=0.003).

Table 2 shows patient characteristics following propensity score matching. After adjusting for confounding variables, age, BMI, and length of follow-up period between surgery and survey were balanced (SMD <0.1).

The primary endpoint, “Satisfaction with Breasts” score measured by the BREAST-Q, was higher in the cryoablation group compared to the BCT group (cryoablation vs. BCT: 71.0±18.6 vs. 56.3±16.5). Similar trends were observed across other scales (Figure 4).

Figure 4 The results of the BREAST-Q score before propensity score matching. *, P<0.05; **, P<0.01. N.S., not significant; BCT, breast-conserving therapy.

Further, after adjusting for patient characteristics (age at treatment, BMI, and length of follow-up period between surgery and survey) using propensity score matching, patients in the cryoablation group exhibited higher levels of satisfaction compared to those in the BCT group (Figure 5).

Figure 5 The results of the BREAST-Q score after adjusting patient background with propensity score matching. *, P<0.05; **, P<0.01. N.S., not significant; BCT, breast-conserving therapy.

Discussion

In this study, the BREAST-Q was used to compare post-operative patient satisfaction between surgical therapy (BCT) and non-surgical therapy (cryoablation) in patients with early breast cancer (Stage 0–1). The results indicated that patients who underwent cryoablation experienced significantly higher satisfaction with their breast cancer treatment. Similar findings were noted for secondary outcomes. Moreover, the results remained consistent even after adjusting for confounding factors such as age at treatment, BMI, and length of the follow-up period between surgery and the survey.

Few studies (7,12) have assessed satisfaction after cryoablation using the BREAST-Q questionnaire and compared it with satisfaction after BCT. Khan et al. showed a significant increase of 12 points (P=0.017) in the Satisfaction with Breast score post cryoablation compared to surgical resection (12). In our study, a greater increase of 14.7 points was observed (cryoablation vs. BCT: 71.0±18.6 vs. 56.3±16.5, P=0.001). We believe that our study included a larger sample size and more detailed analysis compared to Khan et al.’s study (12).

A recent report by the Organization for Economic Co-operation and Development (OECD) (26), reviewed 270 studies that used BREAST-Q post BCT. According to the study, the Satisfaction with Breast parameter of the BREAST-Q had a mean score of 62 (range: 35–79), with a mean follow-up time of 4.0 years. The score in the current study was within the same range (56.3±16.5). In contrast, the score for the primary outcome was significantly higher for the non-surgical cryoablation group (71.0±18.6, mean follow-up time: 4.2 years) than that for the BCT group. This suggests that cryoablation may result in greater patient satisfaction than conventional BCT. Cryoablation has been shown to be safe and effective for patients with hormone receptor-positive breast cancer, tumor size <15 mm, absence of axillary lymph node metastasis, and grade 1 or 2 tumors (8). Cryoablation destroys cancer cells through direct mechanisms, leading to necrotic and/or apoptotic bodies. Unlike lumpectomy, cryoablation does not involve the surgical removal of tissue. Over subsequent weeks and months, the dead tissue is gradually removed or absorbed by the phagocytic activity of inflammatory cells and replaced by a fibrous, collagenous scar.

In this study, the ablated area was replaced with a fibrotic collagenous scar that could be palpated by the patient as a mass. In contrast, BCT excises the mass leaving nothing palpable. Stolpner et al. speculated that awareness of a mass inside the breast might lead to lower satisfaction (27). However, in our study, the cryoablation group scored higher than the BCT group on all BREAST-Q scores. Cryoablation provided patients with a degree of satisfaction that outweighed the presence of remaining lumps in the breast.

This study found that cryoablation resulted in higher patient satisfaction than BCT. We believe that this is partly because cryoablation did not involve excision; therefore, the breast volume did not change before and after treatment, and breast symmetry was not compromised. Previous studies have suggested that breast symmetry influences patient satisfaction (28,29).

Because of improved survival outcomes, breast cancer is increasingly perceived as a chronic disease; thus, survivors’ HRQOL and satisfaction have become a major focus of treatment. Cryoablation resulted in higher HRQOL and patient satisfaction in patients with early-stage breast cancer than in those with BCT. Moreover, cryoablation can be performed as an office surgery under local anesthesia, whereas in Japan, BCT requires general anesthesia and hospitalization. This supports cryoablation as a valuable treatment choice compared to BCT for patients with early-stage and low-grade breast cancer.

We also could not obtain presurgical BREAST-Q assessments due to the retrospective, observational nature of the study, which limited the evaluation of changes in BREAST-Q scores. To address this limitation, it is necessary to establish patient registries for future studies. This study did not include questions regarding the patients’ socioeconomic status (SES). BCT receives insurance coverage, whereas patients must bear additional out-of-insurance expenses for cryoablation. Therefore, it cannot be ruled out that SES may influence the BREAST-Q questionnaire, which may have biased the results of this study. Future studies should evaluate the differences in satisfaction after adjusting for patient background, including SES.

Finally, as a single-center study with a somewhat homogeneous patient population, our findings may lack generalizability. Further investigations, including the establishment of multicenter collaborative research registries are necessary for more in-depth exploration.

Conclusions

Cryoablation resulted in greater patient satisfaction in patients with early-stage breast cancer than in those with BCT. Our findings provide valuable scientific evidence to underpin treatment options for patients with early-stage, low-grade breast cancer. Cryoablation is also used as a local treatment for breast cancer patients with distant metastases that have been controlled through pharmacotherapy (30). Its application in breast cancer treatment is anticipated to become more widespread in the future.

Acknowledgments

We thank the outpatient staff of the Kameda Medical Center who cooperated in the survey.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-24-394/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-394/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-394/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-394/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 (as revised in 2013). The study protocol was approved by the Kameda Medical Center Clinical Research Review Committee (No. 21-036) and met the guidelines of the responsible governmental agency. Informed consent was obtained in the form of opt-out on the web-site.

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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