Abstract
Background
Current decision-making for the treatment of breast cancer liver metastases (BCLM) using ablation lacks strong evidence, especially for patients combined with extrahepatic metastases.
Purpose
To assess whether ablation plus systemic therapy (AS) improves survival outcomes in patients with BCLM compared to systemic therapy alone.
Materials and methods
This retrospective study analyzed patients with BCLM who received either AS or systemic therapy alone. Propensity score matching (PSM) and survival analysis were performed, taking into account factors like the characteristics of primary breast cancer, liver metastases and systemic therapies received.
Results
The study included 1021 female patients, with a median follow-up of 39.6 months. Of these patients, 132 underwent AS and 836 received systemic therapy alone. After PSM, among patients with BCLM (≤3 tumors, each ≤3 cm), the median overall survival (OS) for those treated with AS or systemic therapy alone was 65.5 and 40.4 months, respectively (HR = 0.48, p = .003); in the subset of patients with extrahepatic metastases, the median OS for those treated with AS and systemic therapy alone was 46.4 and 40.8 months, respectively (HR = 0.58, p = .047). Among patients with >3 cm or >3 lesions, the median OS for those treated with AS or systemic therapy alone was 45.2 and 29 months, respectively (HR = 0.67, p = .084).
Conclusions
Among patients with BCLM (≤3 tumors, each ≤3 cm), AS provide longer survival compared to systemic therapy alone, even with extrahepatic metastases. For patients with larger or more numerous metastases (>3 cm or >3 lesions), AS may provide survival benefit, but further validation is needed.
Keywords: Ablation, Breast cancer liver metastases, Liver resection, Systemic therapy
Highlights
-
•
For curatively ablatable BCLM (≤3 tumors, each ≤3 cm), ablation plus systemic therapy resulted in better OS than systemic therapy alone.
-
•
Even with extrahepatic metastases, ablation plus systemic therapy resulted in better OS than systemic therapy alone for curatively ablatable BCLM.
-
•
Ablation plus systemic therapy may offer OS benefit for larger or multiple BCLM tumors (>3 cm or >3 tumor counts) but needed further validation.
1. Introduction
The presence of liver metastases is a significant negative prognostic factor in patients with breast cancer, resulting in extremely poor survival rates without intervention [1]. Breast cancer is the most common cancer worldwide [2]. Approximately 50 % of patients with metastatic breast cancer develop liver metastases [3], and the median overall survival (OS) for patients with untreated breast cancer liver metastases (BCLM) is only 3–6 months after the diagnosis of metastasis [4].
Currently, the primary approach to managing BCLM is systemic therapy. However, it has been demonstrated that local control of oligometastases confined to the liver can be achieved in patients with advanced breast cancer with a combination of local and systemic therapy [5]. In addition, there is evidence that surgical resection can result in a survival benefit for patients with breast cancer and solitary resectable liver metastases [6].
Ablation represents an important local therapeutic option for patients with metastatic tumors, having been used successfully as a palliative treatment that offers potential survival benefits for many patients [7]. Studies have shown that particularly when used in combination with systemic therapy, ablation confers survival benefits for patients with metastases in the liver, lung, bone, and adrenal glands [5,8,9]. However, there remains a lack of high-quality evidence supporting the use of ablation in patients with BCLM. In this study, we endeavored to determine whether patients with BCLM derived benefit from ablation plus systemic therapy (AS), by comparing the length of OS of these patients with those receiving systemic therapy alone. We used propensity score matching (PSM) to minimize biases and approximate the conditions of a randomized controlled trial.
2. Materials and methods
2.1. Study design and participants
This two-center retrospective study involved patients with BCLM diagnosed between January 1, 2011 and December 31, 2022, and follow-up was concluded on October 7, 2023. All procedures were conducted with strict adherence to ethical standards and the study received approval from the Ethics Committee (Institutional Review Board approval number: B2024-096-01; SYSKY-2024-561-01). This retrospective study meets the informed consent exemption. All work is reported in line with the STROBE guidelines [10].
Eligible patients were 18–85 years old and had pathologically confirmed invasive breast cancer, liver metastases confirmed by imaging or pathology, and may have had concurrent metastases at other sites. Excluded patients were those who had primary malignant tumors or metastases not related to breast cancer and those who had incomplete data.
2.2. Ablation procedure
Ablation was performed by interventional radiologists under CT-guidance. The goal of ablation was complete ablation and an ablated tumor margin of ≥5 mm was achieved in all patients. If residual viable tumor was evident on immediate follow-up imaging, additional ablation could be performed at that time.
In general, ablation and chemotherapy were scheduled at least 3 weeks apart to minimize risks associated with chemotherapy-related bone marrow suppression, which typically peaks between 7 and 14 days post-chemotherapy. Patients could undergo multiple ablation sessions as needed.
2.3. Variables
For this study we evaluated various factors potentially affecting local control and OS, including patient age, molecular subtype and American Joint Committee on Cancer (AJCC), 8th edition staging of the primary breast cancer, characteristics of liver metastases evaluated by contrast-enhanced MRI or CT imaging, number and sites of extrahepatic metastases, and number and types of systemic therapies received both after liver metastases were identified.
Molecular subtypes of primary breast cancer were classified by immunohistochemistry as triple-negative, HER2-positive (hormone-receptor positive), HER2-positive (hormone-receptor negative), Luminal A-like, or Luminal B-like.
Characteristics of liver metastases evaluated included location, number, size, and synchronicity. Synchronous and metachronous liver metastases were defined based on whether the diagnoses of primary breast cancer and liver metastases occurred within or beyond a 6-month interval, respectively.
Systemic therapies prior to and following the diagnosis of BCLM were categorized as bone metastasis treatments, cyclin-dependent kinase 4/6 inhibitor (CDK4/6 inhibitors), chemotherapeutic agents, endocrine therapy, HER2-targeted therapy, immune checkpoint inhibitors (ICI), poly ADP-ribose polymerase (PARP) inhibitors, multi-targeted tyrosine kinase inhibitors (MTKI), and other targeted therapies (including drugs targeting epidermal growth factor receptor and mitogen-activated protein kinase kinase).
2.4. Outcomes
The primary study endpoint was the length of OS, measured from the time of first diagnosis of liver metastases. Patients alive at the end of the study period were censored at the date of their last recorded follow-up.
2.5. Statistical analysis
The analyses of continuous variables were performed using either the Student's t-test or the Mann-Whitney U test, based on the distribution characteristics. Either the χ2 test or Fisher's exact test was applied to the categorical data, depending on the scale of the data. To mitigate the impact of selection biases and confounding variables, propensity scores were computed through logistic regression, facilitating a 1:2 patient matching process. In a limited number of subgroup analyses, the PSM method was not used because of small sample size or insignificant differences between groups, and so in these analyses hazard ratio (HR), 95 % confidence interval (CI), and p-values were calculated using data before PSM. Survival rates were calculated via the Kaplan-Meier method and assessed using the Log-rank test. Some calculations of OS and 95 % CI were not possible because patients had high survival rates, were lost to follow-up, or had data censored. Differences of p < .05 were considered statistically significant. Statistical analyses were performed using software R, version 4.2.2 (released October 2022). The code for the analyses is available at https://github.com/Yiquan-Jiang/BCLM-ablation-research/blob/main/Code.
3. Results
3.1. Patient characteristics
Out of 1177 screened patients from 2 centers, patients were excluded as follows: 92 for incomplete systemic therapy records, 2 for missing BCLM location data, 21 for missing maximum diameters of liver metastases, 8 for undergoing concurrent liver resection and AS, and 33 for receiving transarterial chemoembolization or infusion therapy (Fig. 1). As a result, 1021 patients were ultimately included in the study based on the eligibility criteria (100 AS patients, 25 resection plus systemic therapy patients, and 687 systemic therapy alone patients from center 1; 32 AS patients, 28 resection plus systemic therapy patients, and 149 systemic therapy alone patients from center 2), with a median follow-up duration of 39.6 months (interquartile range [IQR]: 35.5, 45.6) after their BCLM diagnosis. Patient characteristics of the entire cohort are summarized in Table 1.
Fig. 1.
Flow diagram of selection of patients with breast cancer liver metastasis (BCLM) for the study and including grouping of patients by liver metastasis treatment feasibility.
Table 1.
Characteristics of 1021 patients with breast cancer and liver metastases (BCLM).
| Characteristic | Total Patients (n = 1021) |
|---|---|
| Age at BCLM diagnosis, median (IQR), yrs | 49 (42, 56) |
| Molecular Subtype, n (%) | |
| Luminal A-like | 110 (10.8) |
| Luminal B-like | 405 (39.7) |
| HER2-positive (HR-negative) | 133 (13) |
| HER2-positive (HR-positive) | 191 (18.7) |
| TNBC | 133 (13) |
| Unknown | 49 (4.8) |
| Primary AJCC Staging, n (%) | |
| I | 70 (6.9) |
| II | 251 (24.6) |
| III | 261 (25.6) |
| IV | 307 (30.1) |
| Unknown | 132 (12.9) |
| Liver Metastases, n (%) | 1021 (100) |
| Extrahepatic metastases, n (%) | 829 (81.2) |
| Liver Metastases Status | |
| Number of tumors, n (%) | |
| 1 | 292 (28.6) |
| 2 | 85 (8.3) |
| 3 | 23 (2.3) |
| ≥4 | 620 (60.8) |
| Unknown | 1 |
| Maximum tumor diameter, median (IQR), mm | 25 (16, 38) |
| Location of metastases in liver, n (%) | |
| Left lobe | 154 (15.1) |
| Right lobe | 248 (24.3) |
| Bilateral lobes | 619 (60.6) |
| Synchronicitya, n (%) | |
| Metachronous metastases | 717 (70.2) |
| Synchronous metastases | 279 (27.3) |
| Unknown | 25 (2.4) |
| Resection, n (%) | 53 (5.2) |
| Ablation, n (%) | 132 (12.9) |
Synchronous and metachronous liver metastases defined based on whether the diagnoses of primary breast cancer and liver metastases occurred within or beyond 6-month interval, respectively.
3.2. Cohort analysis of patients treated with ablation vs. systemic therapy
In the entire cohort, the survival of patients who received AS (n = 132; 2 received cryoablation, 78 received microwave ablation, 34 received radiofrequency ablation, 1 received cryoablation and microwave ablation, 9 received microwave ablation and radiofrequency ablation, and 8 received an unknown type of ablation) were compared to the survival of those who received systemic therapy alone (n = 836). For the entire cohort, before PSM the median OS was 50.7 months (95 % CI: 45.2,75.9) for AS group and 28.3 months (95 % CI: 26.3,31.0) for systemic therapy alone group, resulting in an HR of 0.47 (95 % CI: 0.357, 0.6147; p < .001). After PSM the median OS was 50.6 months (95 % CI: 44.9, 67.2) for those receiving AS (n = 119) and 39.9 months (95 % CI: 30.6, 45.7) for those receiving systemic therapy alone (n = 209), resulting in an HR of 0.64 (95 % CI: 0.47, 0.89; p = .008) (Fig. 2A, Sup Table 1).
Fig. 2.
Survival analyses of patients with breast cancer liver metastasis (BCLM) in the entire cohort (A) or the curatively ablatable group (≤3 tumors, each ≤3 cm) (B), comparing those treated with ablation or systemic therapy alone, before and after propensity score matching (PSM). Abbreviations: PSM, propensity score matching.
3.3. Subgroup analysis of patients with curatively ablatable BCLM (≤3 tumors, each ≤3 cm)
Within the subset of 306 patients deemed to have curatively ablatable liver metastases (≤3 tumors, each ≤3 cm), 79 were treated with AS, 22 underwent liver resection plus systemic therapy, and 205 received systemic therapy alone (Fig. 1, Table 2). Before PSM, the median OS was 65.5 months (95 % CI: 51.6, NA) for those receiving AS and 31 months (95 % CI: 28.9, 45.6) for those receiving systemic therapy, resulting in an HR of 0.45 (95 % CI: 0.3, 0.68; p <.001). After PSM, the median OS was 65.5 months (95 % CI: 46.4, NA) for those receiving AS (n = 61) and 40.4 months (95 % CI: 27.8, 48.5) for those receiving systemic therapy (n = 102), resulting in an HR of 0.48; (95 % CI: 0.3, 0.78; p = .003) (Fig. 2B). In this same subset, the median OS of those treated with AS was 65.5 months (95 % CI: 51.6, NA) while for those who underwent resection plus systemic therapy it was not reached (HR = 1.38; 95 % CI: 0.53, 3.56; p = .51).
Table 2.
Characteristics of patients with breast cancer and liver metastases (BCLM) who were deemed to have curatively ablatable liver metastasis (≤3 tumors, each ≤3 cm), treated with either systemic therapy or ablation, and analyzed before and after propensity score matching (PSM).
| Characteristic | Before PSM |
After PSM |
||||||
|---|---|---|---|---|---|---|---|---|
| Total Patients (n = 284) | Systemic Therapy (n = 205) | Ablation (n = 79) | pa | Total Patients (n = 163) | Systemic Therapy (n = 102) | Ablation (n = 61) | pa | |
| Age at BCLM Diagnosis, mean (SD), yrs | 49 (11) | 49 (11) | 49 (11) | 0.89 | 48 (10) | 48 (10) | 48 (11) | 0.76 |
| Primary Breast Cancer Status | ||||||||
| Molecular Subtype, n (%) | 0.08 | >0.99 | ||||||
| Luminal A-like | 38 (13.4) | 29 (14.1) | 9 (11.4) | 19 (11.7) | 12 (11.8) | 7 (11.5) | ||
| Luminal B-like | 102 (35.9) | 72 (35.1) | 30 (38) | 60 (36.8) | 39 (38.2) | 21 (34.4) | ||
| HER2 positive (HR-negative) | 38 (13.4) | 27 (13.2) | 11 (13.9) | 27 (16.6) | 16 (15.7) | 11 (18) | ||
| HER2 positive (HR-positive) | 59 (20.8) | 45 (22) | 14 (17.7) | 35 (21.5) | 21 (20.6) | 14 (23) | ||
| TNBC | 35 (12.3) | 28 (13.7) | 7 (8.9) | 16 (9.8) | 10 (9.8) | 6 (9.8) | ||
| Unknown | 12 (4.2) | 4 (2) | 8 (10.1) | 6 (3.7) | 4 (3.9) | 2 (3.3) | ||
| AJCC staging, n (%) | 0.32 | 0.92 | ||||||
| I | 20 (7) | 12 (5.9) | 8 (10.1) | 14 (8.6) | 8 (7.8) | 6 (9.8) | ||
| II | 57 (20.1) | 37 (18) | 20 (25.3) | 36 (22.1) | 23 (22.5) | 13 (21.3) | ||
| III | 77 (27.1) | 60 (29.3) | 17 (21.5) | 35 (21.5) | 20 (19.6) | 15 (24.6) | ||
| IV | 89 (31.3) | 67 (32.7) | 22 (27.8) | 55 (33.7) | 36 (35.3) | 19 (31.1) | ||
| Unknown | 41 (14.4) | 29 (14.1) | 12 (15.2) | 23 (14.1) | 15 (14.7) | 8 (13.1) | ||
| Breast Cancer Liver Metastases Status | ||||||||
| Number of tumors, n (%) | 0.14 | 0.91 | ||||||
| 1 | 208 (73.2) | 144 (70.2) | 64 (81) | 128 (78.5) | 79 (77.5) | 49 (80.3) | ||
| 2 | 61 (21.5) | 50 (24.4) | 11 (13.9) | 25 (15.3) | 16 (15.7) | 9 (14.8) | ||
| 3 | 15 (5.3) | 11 (5.4) | 4 (5.1) | 10 (6.1) | 7 (6.9) | 3 (4.9) | ||
| Maximum tumor diameter, median (IQR), mm | 16 (11, 22) | 16 (11, 22) | 18 (11, 24) | 0.27 | 16 (11, 22) | 16 (11, 22) | 17 (10, 21) | 0.94 |
| Location of metastases in liver, n (%) | 0.03 | 0.99 | ||||||
| Left lobe | 87 (30.6) | 72 (35.1) | 15 (19) | 40 (24.5) | 25 (24.5) | 15 (24.6) | ||
| Right lobe | 163 (57.4) | 110 (53.7) | 53 (67.1) | 105 (64.4) | 66 (64.7) | 39 (63.9) | ||
| Bilateral lobes | 34 (12) | 23 (11.2) | 11 (13.9) | 18 (11) | 11 (10.8) | 7 (11.5) | ||
| Synchronicityb, n (%) | 0.59 | 0.96 | ||||||
| Metachronous metastases | 187 (65.8) | 135 (65.9) | 52 (65.8) | 101 (62) | 64 (62.7) | 37 (60.7) | ||
| Synchronous metastases | 90 (31.7) | 66 (32.2) | 24 (30.4) | 56 (34.4) | 34 (33.3) | 22 (36.1) | ||
| Unknown | 7 (2.5) | 4 (2) | 3 (3.8) | 6 (3.7) | 4 (3.9) | 2 (3.3) | ||
| Extrahepatic metastasis, n (%) | 213 (75) | 161 (78.5) | 52 (65.8) | 0.03 | 111 (68.1) | 72 (70.6) | 39 (63.9) | 0.38 |
| Systemic Treatment after BCLM | ||||||||
| Bone metastasis treatment, n (%) | 148 (52.1) | 115 (56.1) | 33 (41.8) | 0.03 | 78 (47.9) | 50 (49.0) | 28 (45.9) | 0.7 |
| CDK4/6 inhibitor, n (%) | 36 (12.7) | 21 (10.2) | 15 (19) | 0.047 | 21 (12.9) | 12 (11.8) | 9 (14.8) | 0.58 |
| Number of chemotherapeutic agents, n (%) | 0.006 | 0.63 | ||||||
| 0 | 31 (10.9) | 15 (7.3) | 16 (20.3) | 19 (11.7) | 10 (9.8) | 9 (14.8) | ||
| 1-3 | 165 (58.1) | 122 (59.5) | 43 (54.4) | 98 (60.1) | 63 (61.8) | 35 (57.4) | ||
| ≥4 | 88 (31) | 68 (33.2) | 20 (25.3) | 46 (28.2) | 29 (28.4) | 17 (27.9) | ||
| Number of endocrine therapy agents, n (%) | 0.59 | 0.86 | ||||||
| 0 | 83 (29.2) | 63 (30.7) | 20 (25.3) | 52 (31.9) | 34 (33.3) | 18 (29.5) | ||
| 1-2 | 128 (45.1) | 92 (44.9) | 36 (45.6) | 63 (38.7) | 38 (37.3) | 25 (41) | ||
| ≥3 | 73 (25.7) | 50 (24.4) | 23 (29.1) | 48 (29.4) | 30 (29.4) | 18 (29.5) | ||
| HER2-targeted therapy, n (%) | 89 (31.3) | 61 (29.8) | 28 (35.4) | 0.36 | 63 (38.7) | 38 (37.3) | 25 (41) | 0.64 |
| ICI, n (%) | 22 (7.7) | 20 (9.8) | 2 (2.5) | 0.04 | 6 (3.7) | 4 (3.9) | 2 (3.3) | >0.99 |
| PARP inhibitor, n (%) | 3 (1.1) | 1 (0.5) | 2 (2.5) | 0.19 | 0 (0) | 0 (0) | 0 (0) | – |
| MTKI, n (%) | 34 (12) | 29 (14.1) | 5 (6.3) | 0.07 | 16 (9.8) | 11 (10.8) | 5 (8.2) | 0.59 |
| Other targeted therapyc, n (%) | 51 (18) | 38 (18.5) | 13 (16.5) | 0.68 | 30 (18.4) | 18 (17.6) | 12 (19.7) | 0.75 |
Based on Welch Two Sample t-test, Pearson's Chi-squared test, Fisher's exact test, or Wilcoxon rank sum test.
Synchronous and metachronous liver metastases defined based on whether the diagnoses of primary breast cancer and liver metastases occurred within or beyond 6-month interval, respectively.
Other targeted therapy included drugs targeting epidermal growth factor receptor (EGFR) and Mitogen-activated protein kinase kinase (MEK).Abbreviations: SD, standard deviation; IQR, interquartile range; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; TNBC, triple-negative breast cancer; CDK4/6, cyclin-dependent kinase 4/6; ICI, Immune checkpoint inhibitors; PARP, poly ADP-ribose polymerase; MTKI, multi-targeted tyrosine kinase inhibitors.
3.4. Subgroup analysis of patients with curatively ablatable BCLM (≤3 tumors, each ≤3 cm) combined with extrahepatic metastases
Within the subset of 213 patients with BCLM (≤3 tumors, each ≤3 cm) combined with extrahepatic metastases, 52 were treated with AS, and 161 received systemic therapy alone (Table 3). Before PSM, the median OS for those receiving AS was 56.8 months (95 % CI: 44.6, 82.4) while for those who received systemic therapy alone was 35.9 months (95 % CI: 27.9, 45.6), resulting in an HR of 0.56 (95 % CI: 0.36, 0.87; p = .011). After PSM, the median OS for those receiving AS (n = 39) was 46.4 months (95 % CI: 39.9, 82.4) while for those who received systemic therapy alone was 40.8 months (95 % CI: 28.9, 48.5), resulting in an HR of 0.58 (95 % CI: 0.34, 0.999; p = .047) (Fig. 3).
Table 3.
Characteristics of BCLM (≤3 tumors, each ≤3 cm) patients with extrahepatic metastases, treated with ablation or systemic therapy alone, and analyzed before and after propensity score matching (PSM).
| Characteristic | Before PSM |
After PSM |
||||||
|---|---|---|---|---|---|---|---|---|
| Total Patients (n = 213) | Systemic Therapy (n = 161) | Ablation (n = 52) | pa | Total Patients (n = 99) | Systemic Therapy (n = 60) | Ablation (n = 39) | pa | |
| Age at BCLM Diagnosis, mean (SD), yrs | 49(10) | 49(10) | 48(12) | 0.86 | 49(11) | 50(10) | 48(11) | 0.41 |
| Primary Breast Cancer Status | ||||||||
| Molecular Subtype, n (%) | 0.23 | 0.98 | ||||||
| Luminal A-like | 32 (15.0 %) | 26 (16.1 %) | 6 (11.5 %) | 8 (8.1 %) | 5 (8.3 %) | 3 (7.7 %) | ||
| Luminal B-like | 80 (37.6 %) | 62 (38.5 %) | 18 (34.6 %) | 38 (38.4 %) | 22 (36.7 %) | 16 (41.0 %) | ||
| HER2 positive (HR-negative) | 22 (10.3 %) | 16 (9.9 %) | 6 (11.5 %) | 13 (13.1 %) | 8 (13.3 %) | 5 (12.8 %) | ||
| HER2 positive (HR-positive) | 43 (20.2 %) | 33 (20.5 %) | 10 (19.2 %) | 21 (21.2 %) | 12 (20.0 %) | 9 (23.1 %) | ||
| TNBC | 26 (12.2 %) | 20 (12.4 %) | 6 (11.5 %) | 14 (14.1 %) | 10 (16.7 %) | 4 (10.3 %) | ||
| Unknown | 10 (4.7 %) | 4 (2.5 %) | 6 (11.5 %) | 5 (5.1 %) | 3 (5.0 %) | 2 (5.1 %) | ||
| AJCC staging, n (%) | 0.19 | 0.92 | ||||||
| I | 12 (5.6 %) | 7 (4.3 %) | 5 (9.6 %) | 9 (9.1 %) | 6 (10.0 %) | 3 (7.7 %) | ||
| II | 44 (20.7 %) | 29 (18.0 %) | 15 (28.8 %) | 25 (25.3 %) | 15 (25.0 %) | 10 (25.6 %) | ||
| III | 63 (29.6 %) | 52 (32.3 %) | 11 (21.2 %) | 27 (27.3 %) | 18 (30.0 %) | 9 (23.1 %) | ||
| IV | 60 (28.2 %) | 47 (29.2 %) | 13 (25.0 %) | 24 (24.2 %) | 13 (21.7 %) | 11 (28.2 %) | ||
| Unknown | 34 (16.0 %) | 26 (16.1 %) | 8 (15.4 %) | 14 (14.1 %) | 8 (13.3 %) | 6 (15.4 %) | ||
| Breast Cancer Liver Metastases Status | ||||||||
| Number of tumors, n (%) | 0.14 | 0.81 | ||||||
| 1 | 151 (70.9 %) | 109 (67.7 %) | 42 (80.8 %) | 76 (76.8 %) | 46 (76.7 %) | 30 (76.9 %) | ||
| 2 | 49 (23.0 %) | 42 (26.1 %) | 7 (13.5 %) | 17 (17.2 %) | 11 (18.3 %) | 6 (15.4 %) | ||
| ≥3 | 13 (6.1 %) | 10 (6.2 %) | 3 (5.8 %) | 6 (6.1 %) | 3 (5.0 %) | 3 (7.7 %) | ||
| Maximum tumor diameter, median (IQR), mm | 16 (11, 22) | 16 (11, 21) | 18 (13, 23) | 0.19 | 17 (10, 22) | 16 (10, 21) | 18 (10, 23) | 0.48 |
| Location of metastases in liver, n (%) | 0.07 | 0.54 | ||||||
| Left lobe | 64 (30.0 %) | 55 (34.2 %) | 9 (17.3 %) | 26 (26.3 %) | 18 (30.0 %) | 8 (20.5 %) | ||
| Right lobe | 121 (56.8 %) | 86 (53.4 %) | 35 (67.3 %) | 58 (58.6 %) | 34 (56.7 %) | 24 (61.5 %) | ||
| Bilateral lobes | 28 (13.1 %) | 20 (12.4 %) | 8 (15.4 %) | 15 (15.2 %) | 8 (13.3 %) | 7 (17.9 %) | ||
| Synchronicityb, n (%) | 0.64 | >0.99 | ||||||
| Metachronous metastases | 154 (72.3 %) | 115 (71.4 %) | 39 (75.0 %) | 72 (72.7 %) | 44 (73.3 %) | 28 (71.8 %) | ||
| Synchronous metastases | 53 (24.9 %) | 42 (26.1 %) | 11 (21.2 %) | 22 (22.2 %) | 13 (21.7 %) | 9 (23.1 %) | ||
| Unknown | 6 (2.8 %) | 4 (2.5 %) | 2 (3.8 %) | 5 (5.1 %) | 3 (5.0 %) | 2 (5.1 %) | ||
| Systemic Treatment after BCLM | ||||||||
| Bone metastasis treatment, n (%) | 141 (66.2 %) | 113 (70.2 %) | 28 (53.8 %) | 0.03 | 61 (61.6 %) | 37 (61.7 %) | 24 (61.5 %) | 0.99 |
| CDK4/6 inhibitor, n (%) | 25 (11.7 %) | 17 (10.6 %) | 8 (15.4 %) | 0.35 | 8 (8.1 %) | 4 (6.7 %) | 4 (10.3 %) | 0.71 |
| Number of chemotherapeutic agents, n (%) | 0.065 | 0.90 | ||||||
| 0 | 17 (8.0 %) | 9 (5.6 %) | 8 (15.4 %) | 8 (8.1 %) | 5 (8.3 %) | 3 (7.7 %) | ||
| 1-3 | 123 (57.7 %) | 93 (57.8 %) | 30 (57.7 %) | 60 (60.6 %) | 35 (58.3 %) | 25 (64.1 %) | ||
| ≥4 | 73 (34.3 %) | 59 (36.6 %) | 14 (26.9 %) | 31 (31.3 %) | 20 (33.3 %) | 11 (28.2 %) | ||
| Number of endocrine therapy agents, n (%) | 0.23 | 0.99 | ||||||
| 0 | 56 (26.3 %) | 42 (26.1 %) | 14 (26.9 %) | 30 (30.3 %) | 18 (30.0 %) | 12 (30.8 %) | ||
| 1-2 | 93 (43.7 %) | 75 (46.6 %) | 18 (34.6 %) | 34 (34.3 %) | 21 (35.0 %) | 13 (33.3 %) | ||
| ≥3 | 64 (30.0 %) | 44 (27.3 %) | 20 (38.5 %) | 35 (35.4 %) | 21 (35.0 %) | 14 (35.9 %) | ||
| HER2-targeted therapy, n (%) | 65 (30.5 %) | 45 (28.0 %) | 20 (38.5 %) | 0.15 | 42 (42.4 %) | 25 (41.7 %) | 17 (43.6 %) | 0.85 |
| ICI, n (%) | 17 (8.0 %) | 15 (9.3 %) | 2 (3.8 %) | 0.25 | 6 (6.1 %) | 4 (6.7 %) | 2 (5.1 %) | >0.99 |
| PARP inhibitor, n (%) | 2 (0.9 %) | 0 (0.0 %) | 2 (3.8 %) | 0.059 | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) | >0.99 |
| MTKI, n (%) | 30 (14.1 %) | 25 (15.5 %) | 5 (9.6 %) | 0.29 | 15 (15.2 %) | 10 (16.7 %) | 5 (12.8 %) | 0.60 |
| Other targeted therapyc, n (%) | 42 (19.7 %) | 30 (18.6 %) | 12 (23.1 %) | 0.48 | 27 (27.3 %) | 17 (28.3 %) | 10 (25.6 %) | 0.77 |
Based on Welch Two Sample t-test, Pearson's Chi-squared test, Fisher's exact test, or Wilcoxon rank sum test.
Synchronous and metachronous liver metastases defined based on whether the diagnoses of primary breast cancer and liver metastases occurred within or beyond 6-month interval, respectively.
Other targeted therapy included drugs targeting epidermal growth factor receptor (EGFR) and Mitogen-activated protein kinase kinase (MEK).Abbreviations: SD, standard deviation: IQR, interquartile range; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; TNBC, triple-negative breast cancer; CDK4/6, cyclin-dependent kinase 4/6; ICI, Immune checkpoint inhibitors; PARP, poly ADP-ribose polymerase; MTKI, multi-targeted tyrosine kinase inhibitors.
Fig. 3.
Survival analyses of patients with breast cancer liver metastasis (BCLM) in the curatively ablatable group (≤3 tumors, each ≤3 cm) even with extrahepatic metastases, comparing those treated with ablation or systemic therapy alone, before and after propensity score matching (PSM).Abbreviations: PSM, propensity score matching.
3.5. Subgroup analysis of patients with BCLM >3 cm or >3 lesions
In 587 patients with BCLM >3 cm or >3 lesions, 39 underwent AS and 548 received systemic therapy alone. Before PSM, the median OS for those receiving AS was 45.2 months (95 % CI: 33.4, 66.8) and for those treated with systemic therapy was 27.0 months (95 % CI: 24.7, 30.6), resulting in an HR of 0.58 (95 % CI: 0.40, 0.83; p = .084). After PSM, the median OS for those receiving AS (n = 35) was 45.2 months (95 % CI: 32.8, 66.8) and for those treated with systemic therapy (n = 69) was 29.0 months (95 % CI: 22.5, 39.9), resulting in an HR of 0.67 (95 % CI: 0.42, 1.06; p = .084) (Fig. 4).
Fig. 4.
Survival analyses of patients with breast cancer liver metastasis (BCLM) in the curatively unablatable group (>3 tumors, or >3 cm), comparing those treated with ablation or systemic therapy alone, before and after propensity score matching (PSM).Abbreviations: PSM, propensity score matching.
3.6. Survival analyses of patients deemed to have surgically resectable BCLM
Resectable BCLM was defined as having certain tumor characteristics (i.e., single tumor ≤5 cm; single tumor in both lobes, each ≤3 cm; or multiple tumors in a single lobe). Within the subset of 469 patients deemed to have resectable liver metastases, 98 were treated with AS, 53 underwent liver resection plus systemic therapy, and 318 received systemic therapy alone. After PSM, there was no significant difference in the median OS for those receiving AS or liver resection plus systemic therapy (HR = 0.93; 95 % CI: 0.39, 2.21; p = .87) (Sup Fig. 1). In this same subset, after PSM, the median OS for those who underwent liver resection plus systemic therapy (n = 44) was 71.7 months (95 % CI: 54.9, NA) and for those receiving systemic therapy alone (n = 72) was 29.3 months (95 % CI: 27.1, 48.5), resulting in an HR of 0.37 (95 % CI: 0.2, 0.7; p = .002) (Sup Fig. 1).
The sequencing and timing of systemic and ablation therapy is presented in Sup Fig. 2 (We subtracted the date of ablation from the date of systemic therapy to calculate the difference in days, and plotted the distribution of this difference).
3.7. Univariate and multivariate log-rank analyses
Univariate and multivariate log-rank analyses were shown in Fig. 5. Multivariate log-rank analyses for OS of all BCLM patients showed shorter OS with TNBC subtype, >3 liver metastases, extrahepatic metastasis, and metachronous metastases. Longer OS was associated with ablation of liver metastases, endocrine therapy, HER2-targeted therapy, and CDK4/6 inhibitor therapy.
Fig. 5.
Univariate and multivariate log-rank analyses of the entire cohort.† Synchronous and metachronous liver metastases defined based on whether the diagnoses of primary breast cancer and liver metastases occurred within or beyond 6-month interval, respectively.‡ Other targeted therapy included drugs targeting epidermal growth factor receptor (EGFR) and Mitogen-activated protein kinase kinase (MEK).Abbreviations: HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer; CDK4/6, cyclin-dependent kinase 4/6; ICI, Immune checkpoint inhibitors; PARP, poly ADP-ribose polymerase; MTKI, multi-targeted tyrosine kinase inhibitors.
4. Discussion
The liver is a frequent site of metastases, including for patients with breast cancer. At present, systemic therapy remains the predominant treatment modality used for those with BCLM [11]. Local treatment of liver metastases, using ablation or resection, is used less often. The treatment of liver metastases that are resistant to systemic therapy poses a particular challenge in this patient population. In a case matched analysis from Europe, it was estimated that only 21 % of patients with BCLM had undergone liver resection, with the remainder receiving systemic therapy [12]. Based on data from our centers, our analysis indicated that 67.0 % (205/306) of patients deemed to have curatively ablatable BCLM (≤3 tumors, each ≤3 cm) received systemic therapy alone, while only 33.0 % (101/306) of those patients underwent either ablation (25.8 %) or resection (7.2 %). Given the emphasis on local treatment at our centers, the proportion of patients with BCLM receiving local therapy may be even lower at many other centers. These findings suggest that local ablation or resection for the liver metastases of patients with BCLM may be underutilized by breast cancer physicians. Outcomes may be enhanced by a greater number of breast cancer physicians recognizing the potential benefits conferred by local ablation on patients with BCLM.
In the treatment of metastatic breast cancer, the role of local therapies targeting liver metastases (e.g., ablation, surgical resection or stereotactic body radiotherapy [SBRT]) compared to systemic treatment alone remains controversial. According to the NCCN and ESMO Clinical Practice Guidelines for Breast Cancer, the management of metastatic breast cancer, including liver metastases, primarily emphasizes systemic therapies. These guidelines do not recommend local interventions, such as ablation, surgical resection or SBRT, as standard treatment for all patients with liver metastases. Instead, local treatments are selectively considered for symptom control or in specific clinical scenarios, such as oligometastatic disease, where the metastatic burden is limited and potentially suitable for curative intervention [13,14].
Currently, prospective clinical trials investigating local therapies for metastatic breast cancer are relatively scarce. NRG-BR002, a randomized Phase IIR/III trial, which included patients with stage IV breast cancer with metastases to sites such as the liver, lungs, bones, pelvis, and distant lymph nodes, evaluated the impact of adding SBRT to standard systemic therapy for patients with oligometastatic breast cancer. The results indicated that the addition of SBRT did not improve progression-free survival (PFS) or OS in patients with oligometastatic breast cancer. Despite the negative outcome of the NRG-BR002 trial, we believe that this conclusion should not be interpreted as "patients with liver metastases cannot benefit from local therapies." Studies have demonstrated that the prognostic impact of metastatic sites differs, with patients having liver metastases exhibiting significantly poorer survival compared to those without liver involvement [15]. Furthermore, recent studies have shown that liver metastases in multiple cancer types reduce the effectiveness of ICIs. Specifically, breast cancer liver metastases exhibit significantly poorer responses to ICIs compared to other metastatic sites [16,17]. Mechanistically, liver metastases are known to impair systemic immunity by promoting CD8+ T cell depletion. Liver metastases attract activated CD8+ T cells, which undergo apoptosis when encountering immunosuppressive FasL + macrophages within the liver. This process establishes a systemic immune desert, thereby reducing peripheral T cell counts and diminishing T cell diversity and function in tumors, as observed in both patients and preclinical models [18,19]. These findings suggest that liver metastases represent a particularly adverse condition, and local treatment of liver metastases may mitigate these negative effects, ultimately benefiting patients.
For resectable liver metastases, surgical resection remains the primary potentially curative treatment option. A meta-analysis showed that the 1-year, 3-year, and 5-year survival rates for patients with BCLM who underwent liver resection were 90 %, 65.9 %, and 53 %, respectively [20]. In our analysis, the median OS of patients receiving AS was comparable to that of patients who underwent resection of liver metastases. These findings provide support for the consideration of ablation therapy as a feasible alternative to resection, particularly for patients who are deemed to have ablatable BCLM.
Because of multifocality and/or insufficient residual liver volume, the majority of liver metastases in patients with BCLM are curatively unablatable/unresectable [21]. Systemic therapy remains the main treatment for these patients, but for the majority the liver metastases are resistant to treatment. In fact, the 5-year survival rate of patients with BCLM receiving systemic therapy alone is only around 20 % [22]. No studies have been published addressing whether patients with BCLM and curatively unablatable/unresectable liver metastases might benefit from ablation therapy. However, there have been some studies of patients with malignant liver tumors suggesting that the combination of liver ablation and systemic immunotherapy may be a promising therapeutic approach [9]. This is supported by findings that ablation promotes tumor necrosis and antigen release, thereby triggering an anti-tumor immune response and enhancing the efficacy of immune checkpoint inhibitors [23]. In our study, for patients with BCLM >3 cm or >3 lesions, the median OS showed no statistical difference between the ablation and systemic therapy groups. However, the median OS was longer in the ablation group, suggesting that ablation may still offer benefits for patients with BCLM >3 cm or >3 lesions. It highlights the need for more higher-quality and larger-scale studies to further inform treatment decision-making. Furthermore, none of these patients received combined treatment with ablation and immune checkpoint inhibitors. Further study is needed to assess the potential effectiveness of combining ablation with immune checkpoint inhibitors in patients with BCLM.
Our study has several limitations. First, it was retrospective in design, and therefore inevitably subject to selection bias. To address this, we meticulously collected comprehensive data, including the characteristics of both the primary tumors and liver metastases, the presence of extrahepatic metastases, and the systemic therapies administered to the patients, all of which are critical prognostic factors. These data were subsequently used to perform PSM in an attempt to minimize bias. Second, the study spanned over a period of 10 years, during which systemic therapy approaches evolved considerably. Over the past decade, significant advancements in systemic therapy for breast cancer have been made, with the introduction of novel agents such as HER2-targeted therapies, CDK4/6 inhibitors, PARP inhibitors, immune checkpoint inhibitors, and multi-targeted tyrosine kinase inhibitors. To minimize potential bias from treatment variations, this study accounted for the use of most of these agents, and PSM was employed to compare patients in the ablation plus systemic therapy group with those receiving systemic therapy alone, in order to control for treatment differences.
In conclusion, among patients with BCLM (≤3 tumors, each ≤3 cm), ablation improved survival compared to systemic therapy alone, even with extrahepatic metastases. For patients with larger or more numerous metastases (>3 cm or >3 lesions), ablation may provide survival benefit, but further validation is needed.
CRediT authorship contribution statement
Xuxiazi Zou: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Hong-Liang Zou: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Xuan Luo: Writing – review & editing, Writing – original draft, Visualization, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Xu-Wei Chen: Writing – original draft, Visualization, Validation, Project administration, Methodology, Investigation, Formal analysis, Data curation. Wei-Ling Huang: Writing – original draft, Visualization, Validation, Project administration, Methodology, Investigation, Formal analysis, Data curation. Chao Zhang: Writing – original draft, Visualization, Validation, Project administration, Investigation, Formal analysis, Data curation. Ge Ren: Writing – original draft, Validation, Software, Resources, Methodology, Investigation, Data curation. Jin-Hua Huang: Writing – review & editing, Writing – original draft, Visualization, Supervision, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Xue Han: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Yi-Quan Jiang: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.
Ethical approval
This cohort study follows the guidelines outlined in the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement for cohort studies and has received approval from the Ethics Committee of the Sun Yat-sen University Cancer Center (B2024-096-01) and Sun Yet-sen Memorial Hospital Ethics Committee (SYSKY-2024-561-01).
Data sharing statement
Data generated or analyzed during the study are available from the corresponding author by request.
Financial support and sponsorship
This study was supported by the National Natural Science Foundation of China-Guangdong Joint Fund (U20A20370); Science and Technology Program of Guangzhou, China SL2023A04J01564; the Guangdong Basic and Applied Basic Research Foundation: 2022A1515110207, 2023A1515110177; the Guangzhou Basic and Applied Basic Research Foundation: 2023A04J1791.
Declaration of competing interests
All authors declare no financial or non-financial competing interests.
Acknowledgement
The authors sincerely thank Yiducloud (Beijing) Technology Ltd. for the establishment of big data intelligence platform at SYSUCC, and Shu-Yi Zheng from Yiducloud for assistance during data collection and analyses.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.breast.2025.103876.
Contributor Information
Xue Han, Email: hanxue@sysucc.org.cn.
Yi-Quan Jiang, Email: jiangyq@sysucc.org.cn.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
References
- 1.Wyld L., Gutteridge E., Pinder S.E., James J.J., Chan S.Y., Cheung K.L., et al. Prognostic factors for patients with hepatic metastases from breast cancer. Br J Cancer. 2003;89:284–290. doi: 10.1038/sj.bjc.6601038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71:209–249. doi: 10.3322/caac.21660. [DOI] [PubMed] [Google Scholar]
- 3.He Z.-Y., Wu S.-G., Peng F., Zhang Q., Luo Y., Chen M., et al. Up-regulation of RFC3 promotes triple negative breast cancer metastasis and is associated with poor prognosis via EMT. Translational Oncology. 2017;10:1–9. doi: 10.1016/j.tranon.2016.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Goldhirsch A., Gelber R.D., Castiglione M. Relapse of breast cancer after adjuvant treatment in premenopausal and perimenopausal women: patterns and prognoses. J Clin Oncol: Official Journal of the American Society of Clinical Oncology. 1988;6:89–97. doi: 10.1200/JCO.1988.6.1.89. [DOI] [PubMed] [Google Scholar]
- 5.Barral M., Auperin A., Hakime A., Cartier V., Tacher V., Otmezguine Y., et al. Percutaneous thermal ablation of breast cancer metastases in oligometastatic patients. CVIR (Cardiovasc Interventional Radiol) 2016;39:885–893. doi: 10.1007/s00270-016-1301-x. [DOI] [PubMed] [Google Scholar]
- 6.Terata K., Imai K., Wakita A., Sato Y., Motoyama S., Minamiya Y. Surgical therapy for breast cancer liver metastases. Transl Cancer Res. 2020;9:5053–5062. doi: 10.21037/tcr-20-1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Stang A., Fischbach R., Teichmann W., Bokemeyer C., Braumann D. A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases. European Journal of Cancer (Oxford, England: 1990) 2009;45:1748–1756. doi: 10.1016/j.ejca.2009.03.012. [DOI] [PubMed] [Google Scholar]
- 8.Meloni M.F., Andreano A., Laeseke P.F., Livraghi T., Sironi S., Lee F.T. Breast cancer liver metastases: US-guided percutaneous radiofrequency ablation--intermediate and long-term survival rates. Radiology. 2009;253:861–869. doi: 10.1148/radiol.2533081968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Nesbit E.G., Donnelly E.D., Strauss J.B. Treatment strategies for oligometastatic breast cancer. Curr Treat Options Oncol. 2021;22:94. doi: 10.1007/s11864-021-00889-2. [DOI] [PubMed] [Google Scholar]
- 10.Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019;13:S31–S34. doi: 10.4103/sja.SJA_543_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Yip C.-H., Newman L.A. American society of clinical oncology, American society for radiation oncology, and society of surgical oncology guideline for management of hereditary breast cancer. JAMA surgery. 2021;156:284–285. doi: 10.1001/jamasurg.2020.6254. [DOI] [PubMed] [Google Scholar]
- 12.Ruiz A., van Hillegersberg R., Siesling S., Castro-Benitez C., Sebagh M., Wicherts D.A., et al. Surgical resection versus systemic therapy for breast cancer liver metastases: results of a European case matched comparison. European Journal of Cancer (Oxford, England: 1990) 2018;95:1–10. doi: 10.1016/j.ejca.2018.02.024. [DOI] [PubMed] [Google Scholar]
- 13.Gradishar W.J., Moran M.S., Abraham J., Abramson V., Aft R., Agnese D., et al. Breast cancer, version 3.2024, NCCN clinical Practice guidelines in oncology. J Natl Compr Canc Netw. 2024;22:331–357. doi: 10.6004/jnccn.2024.0035. [DOI] [PubMed] [Google Scholar]
- 14.Im S.A., Gennari A., Park Y.H., Kim J.H., Jiang Z.F., Gupta S., et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer. ESMO open. 2023;8 doi: 10.1016/j.esmoop.2023.101541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Horn S.R., Stoltzfus K.C., Lehrer E.J., Dawson L.A., Tchelebi L., Gusani N.J., et al. Epidemiology of liver metastases. Cancer Epidemiology. 2020;67 doi: 10.1016/j.canep.2020.101760. [DOI] [PubMed] [Google Scholar]
- 16.Zou Y., Zou X., Zheng S., Tang H., Zhang L., Liu P., et al. Efficacy and predictive factors of immune checkpoint inhibitors in metastatic breast cancer: a systematic review and meta-analysis. Ther Adv Med Oncol. 2020;12 doi: 10.1177/1758835920940928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Emens L.A., Adams S., Barrios C.H., Dieras V., Iwata H., Loi S., et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol. 2021;32:983–993. doi: 10.1016/j.annonc.2021.05.355. [DOI] [PubMed] [Google Scholar]
- 18.Yu J., Green M.D., Li S., Sun Y., Journey S.N., Choi J.E., et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med. 2021;27:152–164. doi: 10.1038/s41591-020-1131-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Hegde P.S., Chen D.S. Top 10 challenges in cancer immunotherapy. Immunity. 2020;52:17–35. doi: 10.1016/j.immuni.2019.12.011. [DOI] [PubMed] [Google Scholar]
- 20.Rangarajan K., Lazzereschi L., Votano D., Hamady Z. Breast cancer liver metastases: systematic review and time to event meta-analysis with comparison between available treatments. Ann R Coll Surg Engl. 2023;105:293–305. doi: 10.1308/rcsann.2021.0308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Vogl T.J., Farshid P., Naguib N.N.N., Zangos S. Thermal ablation therapies in patients with breast cancer liver metastases: a review. Eur Radiol. 2013;23:797–804. doi: 10.1007/s00330-012-2662-4. [DOI] [PubMed] [Google Scholar]
- 22.Eng L.G., Dawood S., Sopik V., Haaland B., Tan P.S., Bhoo-Pathy N., et al. Ten-year survival in women with primary stage IV breast cancer. Breast Cancer Res Treat. 2016;160:145–152. doi: 10.1007/s10549-016-3974-x. [DOI] [PubMed] [Google Scholar]
- 23.Minami Y., Nishida N., Kudo M. Radiofrequency ablation of liver metastasis: potential impact on immune checkpoint inhibitor therapy. Eur Radiol. 2019;29:5045–5051. doi: 10.1007/s00330-019-06189-6. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.