Surgical therapy for breast cancer liver metastases
Review Article on Loco-regional Therapy for Metastatic Breast Cancer

Surgical therapy for breast cancer liver metastases

Kaori Terata1,2, Kazuhiro Imai2, Akiyuki Wakita2, Yusuke Sato2, Satoru Motoyama2, Yoshihiro Minamiya2

1Department of Breast and Endocrine Surgery, Akita University Hospital, Akita, Japan; 2Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan

Contributions: (I) Conception and design: K Terata; (II) Administrative support: Y Minamiya; (III) Provision of study materials or patients: K Terata, Y Minamiya; (IV) Collection and assembly of data: K Terata; (V) Data analysis and interpretation: K Terata; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Kaori Terata, MD, PhD. Department of Breast and Endocrine Surgery, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan. Email:

Abstract: Breast cancer is the most commonly diagnosed cancer in females worldwide. If diagnosed early, patients generally have good outcomes. However, approximately 20% to 30% of all women diagnosed with breast cancer develop metastatic disease. Metastatic breast cancer is incurable, but there is growing evidence that resection or other local therapy for breast cancer liver metastases (BCLM) may improve survival. We aimed to review indications for and outcomes of perioperative liver resection and other local therapies for BCLM. In this series, we reviewed 11 articles (605 patients) focusing on surgical resection and 7 articles (266 patients) describing radiofrequency ablation (RFA) for BCLM. Median disease-free survival (DFS) after surgical resection was 23 months (range, 14–29 months) and median overall survival (OS) was 39.5 months (range, 26–82 months). One, 3- and 5-year survivals were 89.5%, 70%, and 38%, respectively. The factors favoring better outcomes are hormone receptor positive primary breast cancer status, R0 resection, no extrahepatic metastases (EHM), small BCLM, and solitary liver metastases. On the other hand, the median DFS with RFA was 11 months, median OS was 32 months, and the 3- and 5-year OS were 43% and 27%, respectively. The clinical features that are indications for RFA are smaller tumor and higher EHM rate than those favoring surgical resection (2.4 vs. 4.0 cm and 46% vs. 27%). The merits of RFA are its high technical success rate, low morbidity, short hospital stay, and that it can be repeated. Although results are as yet limited, in carefully selected patients, resection or other local therapies such as RFA, render BCLM potentially provide prognostic improvement.

Keywords: Breast cancer; liver metastases; surgical resection; radiofrequency ablation (RFA)

Submitted Mar 20, 2020. Accepted for publication May 15, 2020.

doi: 10.21037/tcr-20-1598


Globally, breast cancer is the most frequently diagnosed malignancy in females. In Japan, during the year 2014, according to the Cancer Information Service at the National Cancer Center of Japan, 76,257 breast cancer cases were diagnosed in Japan. In the United States, 266,120 breast cancer cases were diagnosed in 2018. There were 40,920 deaths due to breast cancer in that year (1). Available data suggest that approximately 20% to 30% of all patients with breast cancer will develop metastatic disease (2). The leading sites of distant metastases are bone (41.1%), lung (22.4%), liver (7.3%), and brain (7.3%) (3). While the liver is not the most common initial location of distant metastases, breast cancer liver metastases (BCLM) are the first site of metastatic disease in 5% to 20% of patients and, furthermore, half of patients develop liver metastases at some point during their clinical course (4,5). Metastatic breast cancer, with the exception of local recurrence, is regarded as being incurable. Ten-year overall survival (OS) of patients given systemic therapy is about 5%. Moreover, only 2–3% of patients maintain a complete response for more than 20 years (6,7).

Recent evidence suggests that improved systemic treatments are resulting in increased progression-free survival (PFS) and/or OS outcomes. Since the 1990s, chemotherapy has improved the outcomes of metastatic breast cancer patients (8). From the 2000s, especially, molecularly-targeted therapies such as anti-human epidermal growth factor receptor type 2 (HER2) agents, including trastuzumab, pertuzumab and T-DM1 (9,10), mTOR inhibitors and CDK4/6 combined hormonal therapy (11-13), immune checkpoint inhibitors (ICI) such as humanized monoclonal anti-PD-L1 antibody (Atezolizumab) (14), and PARP inhibitors have shown efficacy for BReast CAncer gene (BRCA)-positive HER2 negative metastatic breast cancers (15), thereby contributing to better outcomes. Liver metastases have long been regarded as being incurable and patients generally have poor outcomes, such that treatment is palliative, with the goals being improved quality of life and prolonged survival.

Since there are numerous systemic therapy drugs for metastatic breast cancer, surgery for BCLM has been regarded as being too aggressive for many patients. However, there is growing evidence that resection and other local therapies for BCLM may contribute not only to assessing histological information and the subtype (positivity for estrogen receptor, progesterone receptor, HER2) of metastatic tumors, while also providing a survival benefit. Since 2000, number of studies have examined surgical treatment of BCLM (16-30). The prior studies tended, however, to have limited sample sizes, and the patient selection criteria differed among them. However, some clinical benefits were obtained. Moreover, recent results have shown that patients with solitary liver metastases or oligo-metastatic breast cancer might benefit from local therapies (31,32).

We aimed to review the indications and outcomes of perioperative liver resection and other local therapies for BCLM.


We searched the PubMed database using the terms “breast cancer”, “liver metastases”, and “surgery”. Since the aforementioned major advances in drug therapies (9-11,33) and advancements in surgical techniques, we identified major studies published after 2010 such that this review covers the two decades between 2000 and the present.


Liver resection

This review covers 11 series (34-44), totaling 605 patients. The author, name of the journal, time span of the study, country, and number of patients are listed in Table 1. The studies were published between 2012 and 2018. In nearly all of the series, the study period started around or after 2000, though two series were started in the 1980 which included more than 100 patients in each series (42,43). The median number of patients was 43 (range, 12–131). Six studies (34,35,40-42,44) were prospective and two (38,43) were retrospective. Three were case control studies (36,38,44). Nine were single center analyses (34-42) and two were multicenter analyses (43,44). Five series consisted of patients who had undergone radiofrequency ablation (RFA) (35-39). Several reviews on liver resection have been reported for the last decade (45-51). As the authors investigated, we summarized the data of primary tumor, clinical outcomes, and prognostic factors in this review.

Table 1
Table 1 Details and clinical outcomes of BCLM
Full table

Primary tumor

The major histological type was invasive ductal carcinoma, accounting for a median 83% (range, 12–92%) of cases. TNM stage was used in most studies, with T and N being reported for 7 series (34-36,38,40,43,44). The median percentage of cases with a T1 or T2 primary tumor diagnosis was 83% (54–92%). Approximately half of the total patients (52.5%, range, 28–71%). The M status was reported for only 3 series (34,38,40), with the percentages having distant metastases at the primary diagnosis being 0%, 10%, and 32%. Nine studies (34-40,43,44) included hormone receptor status and seven (34,35,37,38,40,43,44) HER2 receptor status. The median estrogen and progesterone receptor positive rates were 75% (range, 45–82%) and 55% (range, 9–82%), respectively. HER-2 receptor status was positive in 39% (range, 14–55%) of studies assessing this factor.

Clinical outcomes of hepatic resection for BCLM

Table 1 shows the BCLM information. The median time to diagnosis of liver metastases was 34 months (range, 20–60 months) for 8 studies. Eight reports described a median maximal tumor size of 4 cm (range, 1.8–5.2 cm). The median rate of extrahepatic metastases (EHM) was 26.5% (range, 7–45%). Major resection (three or more segments) was performed in 47% (259/556) of patients (median 42.5%, range 29–69%). The microscopic negative margins (R0) rate was reported for 9 studies, and the median was 86% (range, 53–92%), while the recurrence rate was 42.5% (153/360) with a median value of 40% (range, 14–52%). The median follow-up time was 55 months (range, 22–69 months). Median DFS was 23 months (range, 14–29 months) and median OS was 39.5 months (range, 26–82 months). The 1-, 3-, and 5-year OS rates were 89.5% (range, 80–100%), 70% (range, 46–81%), and 38% (range, 11–69%), respectively. These studies had different numbers of patients, clinical features, selected cohorts, and designs, such that the data must be carefully interpreted. As to systemic therapy, 6 articles described systemic therapies (36,37,40-43), including hormone administration with and without chemotherapy (doxorubicin, taxol, capecitabine, gemcitabine) and/or trastuzumab or lapatinib. Among the patients included in this review, none had received the newer targeted therapies such as pertuzumab, CDK 4/6 inhibitors, ICI, and so on.

Prognostic factors

The factors found to independently impact outcomes after BCLM resection are listed in Table 2. Seven studies showed positive hormone receptor status of the primary breast cancer to be associated with better OS after surgical removal of liver metastases (three multivariate and four univariate analyses) (34,36-40,42). Microscopic negative margins (R0) were associated with better OS (two multivariate and two univariate analyses) (35,37,41,43). Three multivariate analyses showed EHM to be associated with poorer OS. BCLM less than 3 cm in maximum diameter was associated with better OS (43), while liver metastases 3.5 cm or larger were associated with poorer PFS (39), according to three multivariate analyses (35,39,40). Univariate analysis also showed BCLM size to be related to outcomes. One report of multivariate and one of univariate analysis showed that patients with solitary liver metastases had better OS (40,42) and that the number of metastases was associated with DFS and OS (38,41). Patients with DFS of 4 years or less had poorer OS and PFS on multivariate analysis, whereas those with DFS of less than 2 years had poorer OS on univariate analysis. Evaluation according to the RECIST criteria showed a lack of response to pre-operative systemic therapy to be associated with progressive disease, and thereby poorer OS (34,37). Abbot et al. reported that patients with a partial response to chemotherapy had a median survival of nearly 80 months, as compared to approximately 30 months for patients with a less than partial response (34). The other primary tumor characteristics, i.e., T stage, lymph node metastases and tumor grade also influenced OS.

Table 2
Table 2 Positive prognostic factors and safety of treating BCLM
Full table


According to the 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4) (52), “Oligometastatic disease is defined as low volume metastatic disease with limited number and size of metastatic lesions (up to 5 and not necessarily in the same organ), potentially amenable for local treatment, aimed at achieving a complete remission status.” In colorectal cancer cases, resection of liver metastases is a well-established treatment (53,54). However, this strategy remains controversial for BCLM, even with oligometastases. More than 50% of the patients in the reports reviewed herein had solitary metastases (34,36,37,39-41,43). Dittmar et al. noted that significantly more long-term survivors, with survival reaching 60 months or more in some cases, had solitary tumors (35). In terms of prognostic factors, solitary liver metastases were associated with better OS (40,42) (m1, u1) and the number of metastases was related to both DFS and OS (38,41). Weinrich et al., studying resection of isolated liver metastases (41), found that 16 of 29 female patients (55%) had one BCLM and 6 (21%) had two BCLMs. Median time to diagnosis of BCLM was 55 months (range, 1–77 months) months. The 1-year survival rate was 86% in patients with and 37.5% in those without resection. R0 resection, fewer liver metastases, and a longer interval to diagnosis of BCLM were found to be significant prognostic factors.

Ruiz et al. (42) reported a series of patients undergoing “repeat hepatectomy”. The single hepatectomy group (N=120) was compared with those who underwent repeat hepatectomy (N=19). The proportion of patients with solitary liver metastases was 39% in the single hepatectomy group and 53% in the repeat hepatectomy group. After the first hepatectomy, patients who received repeat hepatectomy had longer survival than those who had undergone single hepatectomy (95% and 84% vs. 50% and 38% at 3 and 5 years, respectively) (P=0.002). Median survivals were 35 and 100 months, respectively. In terms of the number of metastatic tumors, patients with a single BCLM at first hepatectomy had 3- and 5-year OS rates of 76% and 76% compared with rates of 51% and 17% in patients with multiple metastases (P=0.023). Prognostic factors after repeat hepatectomy included a time interval between breast cancer diagnosis and first hepatectomy of more than 2 years, a limited hepatectomy, solitary metastases, positive progesterone receptor status, and chemotherapy following repeat hepatectomy. The results of Ruiz et al. suggest that repeat hepatectomy is potentially curative when combined with systemic therapy.

Recent studies demonstrated that subgroups of these heterogeneous patient populations with oligometastatic disease benefit from additional local or locoregional treatment, with improved survival rates after R0 resection of BCLM, as compared to systemic treatment alone (42,44,55).

Case control study

To date, there have been no reports of prospective randomized trials examining resection of BCLM. Case control studies have been conducted to determine the actual benefits of surgical treatment (36,38,44). Mariani et al. (36) reported 51 patients with BCLM who were individually matched with patients receiving systemic treatment only. None had more than 4 BCLM, and most of the cases fewer than 4. The study group was matched with the control patients for age, year of breast cancer diagnosis, time to metastases, TNM stage, hormone receptor status and tumor pathology. The 3-year survival rates of surgically treated and non-surgically treated patients were 80.7% and 50.9% (P<0.0001), respectively. Ruiz et al. (44) reported a case-matched comparison of surgical resection versus systemic therapy for BCLM using data from European patients. Matching was based on age, decade when diagnosed, time to metastases, maximum size of metastases, single or multiple tumors, chemotherapy, and hormonal or targeted therapy after diagnosis. Propensity score matching was used to create a subset of patients with similar characteristics and a similar likelihood of undergoing surgery. The median OS of patients receiving systemic treatment combined with liver resection and systemic treatment only were 82 and 31 months (P<0.001), with 3-year OS of 81% and 69% and 5-year OS of 33% and 24%, respectively. Patients who received systemic therapy combined with liver resection lived more than twice as long as those given systemic therapy alone. According to Cox regression results, patients given systemic treatment combined with liver resection were less likely to die than those receiving systemic treatment alone [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15–0.52; P<0.001]. Liver resection is thus potentially effective for appropriately selected cases.

Sadot et al. (56) also performed a case-control study. The purpose of the study was to compare outcomes in patients with isolated BCLM who underwent surgery and/or ablation to those of patients who received systemic therapy alone. In total, 167 patients were studied, including 69 and 98 given surgery/ablation and medical treatments, respectively, with a median follow-up of 73 months. Patients in the surgical group tended to have estrogen receptor positive tumors and to receive adjuvant chemotherapy and radiotherapy for their primary breast tumor. The hepatic tumor volume was smaller and the time to diagnosis of BCLM was significantly longer (53 vs. 30 months) in the surgical cohort. There was no significant difference in OS between the surgical and systemic therapy groups (median OS: 50 vs. 45 months; 5-year OS: 38% vs. 39%). Although hepatic resection and/or ablation was not associated with a survival advantage, the surgical treatment group had a median recurrence-free interval of 28.5 months, and 10 patients (15%) were recurrence free after 5 years. In summary, surgical treatment of BCLM might be applicable in carefully selected patients in whom the goal is to minimize or avoid systemic chemotherapy.

Mortality and morbidity

Postoperative mortality and morbidity are shown in Table 2. Postoperative mortality was 0% in five reports, 2% in one report, and 5% in one report. Median postoperative morbidity was 28% (range, 18–42%). Major complications developed in 3.5–12% of cases (34,42-44) and included multiple organ failure, biliary leakage, both with and without the need for collection of infectious fluid, biliary fistula, infected intra-abdominal fluid drainage, and requiring percutaneous drainage. The median hospital stay was 8.5 days (range, 6–11 days).

Other local treatments: RFA

RFA (57-63), cryoablation (CRA) (64), stereotactic radiofrequency ablation (SRFA) (65), brachytherapy (66), and transarterial chemoembolization (TACE) (67) are among the local treatments available for BCLM.

RFA is particularly safe and effective, and has been widely reported as a local treatment for BCLM. This part covers 7 reports, totaling 225 patients on RFA published from 2007 to 2018. These studies were conducted during the period from 1996 to 2015. The median number of patients is 43 (range, 12–69) and the median number of treated tumors is 87 (range, 13–135), with an average of 1.9 tumors (range, 1.1–2.1) per patient. Two series examined conventional computed tomography-guided RFA and 5 series focused on conventional ultrasound-guided RFA. The mean size of metastases was 2.4 cm (range, 2–3.5 cm). The mean percentage of patients with EHM was 36% (range, 40–83%). The median complete response rate was 86% (range, 67–97%). The median rate of solitary BCLM was 55.5% (range, 26–62%). Median follow-up in these reports was 24 months, the median DFS was 11 months, the median OS was 32 months, and the respective 3- and 5-year OS rates were 43% and 27%. Complication rates were lower than with surgical resection. Four studies had major complication rates of 0% (57,59,60,62), the others of 1.1%, 2.3%, and 6.9% (severe intrahepatic bleeding, injury to the bile duct, thrombosis of the portal branch, sepsis, and cholecystitis.). The median hospitalization period was 2 days (range, 1–5 days).

As to repeat RFA, Sofocleous et al. reported a patient who underwent three RFA sessions, achieving intervention-associated local control for 47 months (57). Jakobs et al. reported that local tumor progression was observed in 15 of 111 metastases at 3 months of follow-up. Five patients received repeat RFA in their study (58). Meloni et al. (59) reported that a BCLM exceeding 2.5 cm in size was related to poor outcomes. Bai et al. (63) reported 69 patients with 135 liver metastases. Local tumor progression was observed in 8 of these patients, 4–8 months after RFA. Local tumor progression rates for tumors with a margin of 0–5, >5–10 and >10 mm were 38.9%, 3.6%, and 0%, respectively. Among these 8 patients, 7 required repeat RFA. Fifty-five percent presented with new intrahepatic metastases, among these, 42% (16/38) underwent repeat RFA, while others received chemotherapy or TACE.

As several reviews on RFA reported (51,68,69), the clinical benefits of RFA included smaller tumor size and the higher EHM rate, as compared to surgical resection (2.4 vs. 4.0 cm and 46% vs. 27%). The merits of RFA include its high technical success rate (58,60,63), low morbidity, short hospitalization (57,59), and that it can be repeated. However, liver resection is indicated for larger tumors.

Future perspectives

BCLM is reported to potentially be effective (or curative) with surgery, which is clinically applicable to highly selected patients. Evidence of circulating tumor DNA (ctDNA) is growing. In early breast cancer, postsurgical levels of ctDNA were found to predict poor outcomes and risk of recurrence (70,71). Moreover, in the metastatic setting, ctDNA may represent a measure of treatment responses (72,73). The important clinical questions regarding surgical resection for BCLM are “when”, “to whom”, “whether or not to continue systemic therapy (and when systemic therapy should be resumed)”, and “whether or not the cancer can potentially be cured”. Although further investigations are needed, the evidence indicates that ctDNA might answer these questions and facilitate selecting the patients who would benefit from surgical resection of BCLM.

On the other hand, cost-utility is also an important issue in cancer therapy. Spolverato et al. (74) evaluated the cost-effectiveness of liver resection. Three groups, liver resection followed by postoperative conventional systemic therapy, conventional therapy alone, and newer targeted therapy alone, were compared by applying the Markov model and Monte-Carlo simulation. The authors concluded that liver resection is potentially more cost-effective than systemic therapy alone, especially in patients positive for the estrogen receptor and/or receiving newer systemic therapies. These data add to the broader discussion of how to best treat patients with BCLM.

As for RFA, combinations with other therapies such as ICI may enhance antitumor immunity. Not only radiotherapy (75,76) but also RFA with ICI can trigger a distal antitumor response which would then lead to an abscopal immune-priming effect (77-79). RFA was reported to increase the antigen specific CD8+ T cells at the site of the residual tumor in a murine model with colorectal cancer (80). Adding a PD-1 inhibitor to RFA reduced the tumor volume and prolonged survival. Pre-operative RFA combined with agents targeting the PD-1/PD-L1 axis could be a promising future approach for managing high-risk patients. Although further investigations are needed, adding RFA to ICI appears to provide an effective strategy for BCLM.


The effectiveness of local treatment for BCLM is still controversial. The data reviewed herein were heterogeneous and selection bias is a weakness. A multicenter randomized controlled trial, examined the potential survival benefit of surgical resection for highly selected patients. RFA has the merits of being repeatable, with low morbidity, and high technical success rates, while being applicable to patients with EHM. Furthermore, new interventions targeting molecules such as ctDNA, and strategies combining ICI targeting the PD-1/PD-L1 axis with other treatments, might have benefits when used with surgical treatment or RFA. In terms of cost-effectiveness, selected patients might benefit from these local treatments during their clinical courses. These newer approaches might, in future, answer some of the clinical questions regarding which patients would benefit from surgical resection or RFA of BCLM.


Funding: None.


Provenance and Peer Review: This article was commissioned by the Guest Editors (Tadahiko Shien and Kaori Terata) for the series “Loco-regional therapy for metastatic breast cancer” published in Translational Cancer Research. The article was sent for external peer review organized by the Guest Editors and the editorial office.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at The series “Loco-regional therapy for metastatic breast cancer” was commissioned by the editorial office without any funding or sponsorship. KT served as the unpaid Guest Editor of the series. The authors have no other 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.

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:


  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J. Clin. 2018;68:7-30. [Crossref] [PubMed]
  2. Bishop AJ, Ensor J, Moulder SL, et al. Prognosis for patients with metastatic breast cancer who achieve a no-evidence-of-disease status after systemic or local therapy. Cancer 2015;121:4324-32. [Crossref] [PubMed]
  3. Berman AT, Thukral AD, Hwang WT, et al. Incidence and patterns of distant metastases for patients with early-stage breast cancer after breast conservation treatment. Clin Breast Cancer 2013;13:88-94. [Crossref] [PubMed]
  4. Hoe AL, Royle GT, Taylor I. Breast liver metastases--incidence, diagnosis and outcome. J R Soc Med 1991;84:714-6. [Crossref] [PubMed]
  5. Zinser JW, Hortobagyi GN, Buzdar AU, et al. Clinical course of breast cancer patients with liver metastases. J Clin Oncol 1987;5:773-82. [Crossref] [PubMed]
  6. Greenberg PA, Hortobagyi GN, Smith TL, et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996;14:2197-205. [Crossref] [PubMed]
  7. Rahman ZU, Frye DK, Smith TL, et al. Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference. Cancer 1999;85:104-11. [Crossref] [PubMed]
  8. Gennari A, Conte P, Rosso R, et al. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005;104:1742-50. [Crossref] [PubMed]
  9. Baselga J, Cortés J, Kim SB, et al. CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109-19. [Crossref] [PubMed]
  10. Verma S, Miles D, Gianni L, et al. EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783-91. [Crossref] [PubMed]
  11. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520-9. [Crossref] [PubMed]
  12. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016;17:425-39. [Crossref] [PubMed]
  13. Sledge GW Jr, Toi M, Neven P, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol 2019;6:116-24. [Crossref] [PubMed]
  14. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018;379:2108-21. [Crossref] [PubMed]
  15. Robson ME, Tung N, Conte P, et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol 2019;30:558-66. [Crossref] [PubMed]
  16. Raab R, Nussbaum KT, Behrend M, et al. Liver metastases of breast cancer: results of liver resection. Anticancer Res 1998;18:2231-3. [PubMed]
  17. Selzner M, Morse MA, Vredenburgh JJ, et al. Liver metastases from breast cancer: long-term survival after curative resection. Surgery 2000;127:383-9. [Crossref] [PubMed]
  18. Yoshimoto M, Tada T, Saito M, et al. Surgical treatment of hepatic metastases from breast cancer. Breast Cancer Res Treat 2000;59:177-84. [Crossref] [PubMed]
  19. Pocard M, Pouillart P, Asselain B, et al. Hepatic resection in metastatic breast cancer: results and prognostic factors. Eur J Surg Oncol 2000;26:155-9. [Crossref] [PubMed]
  20. Seifert JK, Weigel TF, Gonner U, et al. Liver resection for breast cancer metastases. Hepatogastroenterology 1999;46:2935-40. [PubMed]
  21. Maksan SM, Lehnert T, Bastert G, et al. Curative liver resection for metastatic breast cancer. Eur J Surg Oncol 2000;26:209-12. [Crossref] [PubMed]
  22. Karavias DD, Tepetes K, Karatzas T, et al. Liver resection for metastatic non-colorectal non-neuroendocrine hepatic neoplasms. Eur J Surg Oncol 2002;28:135-9. [Crossref] [PubMed]
  23. Marín Gómez LM, Jiménez Romero C, Pérez Saborido B, et al. Surgical treatment of liver metastasis from breast cancer. Hepatogastroenterology 2004;51:586-8. [PubMed]
  24. Carlini M, Lonardo MT, Carboni F, et al. Liver metastases from breast cancer. Results of surgical resection. Hepatogastroenterology 2002;49:1597-601. [PubMed]
  25. Elias D, Maisonnette F, Druet-Cabanac M, et al. An attempt to clarify indications for hepatectomy for liver metastases from breast cancer. Am J Surg 2003;185:158-64. [Crossref] [PubMed]
  26. Vlastos G, Smith DL, Singletary SE, et al. Longterm survival after an aggressive surgical approach in patients with breast cancer hepatic metastases. Ann Surg Oncol 2004;11:869-74. [Crossref] [PubMed]
  27. Arena E, Ferrero S. Surgical treatment of liver metastases from breast cancer. Minerva Chir 2004;59:7-15. [PubMed]
  28. Okaro AC, Durkin DJ, Layer GT, et al. Hepatic resection for breast cancer metastases. Ann R Coll Surg Engl 2005;87:167-70. [Crossref] [PubMed]
  29. Sakamoto Y, Yamamoto J, Yoshimoto M, et al. Hepatic resection for metastatic breast cancer: prognostic analysis of 34 patients. World J Surg 2005;29:524-27. [Crossref] [PubMed]
  30. d'Annibale M, Piovanello P, Cerasoli V, et al. Liver metastases from breast cancer: the role of surgical treatment. Hepatogastroenterology 2005;52:1858-62. [PubMed]
  31. Tait CR, Waterworth A, Loncaster J, et al. The oligometastatic state in breast cancer:hypothesis or reality. Breast. 2005;14:87-93. [Crossref] [PubMed]
  32. Pagani O, Senkus E, Wood W, et al. ESO-MBC Task Force. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 2010;102:456-63. [Crossref] [PubMed]
  33. Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007;369:29-36. [Crossref] [PubMed]
  34. Abbott DE, Brouquet A, Mittendorf EA, et al. Resection of liver metastases from breast cancer: Estrogen receptor status and response to chemotherapy before metastasectomy define outcome. Surgery 2012;151:710-6. [Crossref] [PubMed]
  35. Dittmar Y, Altendorf-Hofmann A, Schule S, et al. Liver resection in selected patients with metastatic breast cancer: A single-centre analysis and review of literature. J Cancer Res Clin Oncol 2013;139:1317-25. [Crossref] [PubMed]
  36. Mariani P, Servois V, De Rycke Y, et al. Liver metastases from breast cancer: Surgical resection or not? A case-matched control study in highly selected patients. Eur J Surg Oncol 2013;39:1377-83. [Crossref] [PubMed]
  37. Kostov DV, Kobakov GL, Yankov DV. Prognostic factors related to surgical outcome of liver metastases of breast cancer. J Breast Cancer 2013;16:184-92. [Crossref] [PubMed]
  38. Polistina F, Costantin G, Febbraro A, et al. Aggressive treatment for hepatic metastases from breast cancer: results from a single center. World J Surg 2013;37:1322-32. [Crossref] [PubMed]
  39. Treska V, Cerna M, Liska V, et al. Surgery for breast cancer liver metastases - factors determining results. Anticancer Res 2014;34:1281-6. [PubMed]
  40. Bacalbasa N, Dima SO, Purtan-Purnichescu R, et al. Role of surgical treatment in breast cancer liver metastases: a single center experience. Anticancer Res 2014;34:5563-8. [PubMed]
  41. Weinrich M, Weiß C, Schuld J, et al. Liver resections of isolated liver metastasis in breast cancer: results and possible prognostic factors. HPB Surg 2014;2014:893829.
  42. Ruiz A, Castro-Benitez C, Sebagh M, et al. Repeat Hepatectomy for Breast Cancer Liver Metastases. Ann Surg Oncol 2015;22:S1057-66. [Crossref] [PubMed]
  43. Margonis GA, Buettner S, Sasaki K, et al. The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: A multi-institutional analysis. HPB 2016;18:700-5. [Crossref] [PubMed]
  44. Ruiz A, van Hillegersberg R, Siesling S, et al. Surgical resection versus systemic therapy for breast cancer liver metastases: Results of a European case matched comparison. Eur J Cancer 2018;95:1-10. [Crossref] [PubMed]
  45. Howlader M, Heaton N, Rela M. Resection of liver metastases from breast cancer: towards a management guideline. Int J Surg 2011;9:285-91. [Crossref] [PubMed]
  46. Chua TC, Saxena A, Liauw W, et al. Hepatic resection for metastatic breast cancer: a systematic review. Eur J Cancer 2011;47:2282-90. [Crossref] [PubMed]
  47. Fairhurst K, Leopardi L, Satyadas T, et al. The safety and effectiveness of liver resection for breast cancer liver metastases: A systematic review. Breast 2016;30:175-84. [Crossref] [PubMed]
  48. Yoo TG, Cranshaw I, Broom R, et al. Systematic review of early and long-term outcome of liver resection for metastatic breast cancer: Is there a survival benefit? Breast 2017;32:162-72. [Crossref] [PubMed]
  49. Golse N, Adam R. Liver Metastases From Breast Cancer: What Role for Surgery? Indications and Results. Clin Breast Cancer 2017;17:256-65. [Crossref] [PubMed]
  50. Tasleem S, Bolger JC, Kelly ME, et al. The role of liver resection in patients with metastatic breast cancer: a systematic review examining the survival impact. Ir J Med Sci 2018;187:1009-20. [Crossref] [PubMed]
  51. Bale R, Putzer D, Schullian P. Local Treatment of Breast Cancer Liver Metastasis. Cancers (Basel) 2019;11:1341. [Crossref] [PubMed]
  52. Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†. Ann Oncol 2018;29:1634-57. [Crossref] [PubMed]
  53. Sugihara K, Uetake H. Therapeutic strategies for hepatic metastasis of colorectal cancer: overview. J Hepatobiliary Pancreat Sci 2012;19:523-7. [Crossref] [PubMed]
  54. Wicherts DA, de Haas RJ, Salloum C, et al. Repeat hepatectomy for recurrent colorectal metastases. Br J Surg 2013;100:808-18. [Crossref] [PubMed]
  55. Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol 2011;8:378-82. [Crossref] [PubMed]
  56. Sadot E, Lee SY, Sofocleous CT, et al. Hepatic Resection or Ablation for Isolated Breast Cancer Liver Metastasis: A Case-control Study With Comparison to Medically Treated Patients. Ann Surg 2016;264:147-54. [Crossref] [PubMed]
  57. Sofocleous CT, Nascimento RG, Gonen M, et al. Radiofrequency ablation in the management of liver metastases from breast cancer. AJR Am J Roentgenol 2007;189:883-9. [Crossref] [PubMed]
  58. Jakobs TF, Hoffmann RT, Schrader A, et al. CT-guided radiofrequency ablation in patients with hepatic metastases from breast cancer. Cardiovasc. Intervent Radiol 2009;32:38-46. [Crossref] [PubMed]
  59. Meloni MF, Andreano A, Laeseke PF, et al. Breast cancer liver metastases: US-guidedpercutaneousradiofrequencyablation–intermediateandlong-termsurvivalrates. Radiology 2009;253:861-9. [Crossref] [PubMed]
  60. Carrafiello G, Fontana F, Cotta E, et al. Ultrasound-guided thermal radiofrequency ablation (RFA) as an adjunct to systemic chemotherapy for breast cancer liver metastases. Radiol Med 2011;116:1059-66. [Crossref] [PubMed]
  61. Veltri A, Gazzera C, Barrera M, et al. Radiofrequency thermal ablation (RFA) of hepatic metastases (METS) from breast cancer (BC): An adjunctive tool in the multimodal treatment of advanced disease. Radiol Med 2014;119:327-33. [Crossref] [PubMed]
  62. Kümler I, Parner VK, Tuxen MK, et al. Clinical outcome of percutaneous RF-ablation of non-operable patients with liver metastasis from breast cancer. Radiol Med 2015;120:536-41. [Crossref] [PubMed]
  63. Bai XM, Yang W, Zhang ZY, et al. Long-term outcomes and prognostic analysis of percutaneous radiofrequency ablation in liver metastasis from breast cancer. Int J Hyperthermia 2019;35:183-93. [Crossref] [PubMed]
  64. Zhang W, Yu H, Guo Z, et al. H. Percutaneous cryoablation of liver metastases from breast cancer: Initial experience in 17 patients. Clin Radiol 2014;69:231-8. [Crossref] [PubMed]
  65. Bale R, Richter M, Dunser M, et al. Radiofrequency Ablation for Breast Cancer Liver Metastases. J Vasc Interv Radiol 2018;29:262-7. [Crossref] [PubMed]
  66. Wieners G, Mohnike K, Peters N, et al. Treatment of hepatic metastases of breast cancer with CT-guided interstitial brachytherapy-a phase II-study. Radiother Oncol 2011;100:314-9. [Crossref] [PubMed]
  67. Eichler K, Jakobi S, Gruber-Rouh T, et al. Transarterial chemoembolisation (TACE) with gemcitabine: phase II study in patients with liver metastases of breast cancer. Eur J Radiol 2013;82:e816-22. [Crossref] [PubMed]
  68. Ruiterkamp J, Ernst MF. The role of surgery in metastatic breast cancer. Eur J Cancer 2011;47 Suppl 3:S6-22. [Crossref] [PubMed]
  69. Vogl TJ, Farshid P, Naguib NN, et al. Thermal ablation therapies in patients with breast cancer liver metastases: a review. Eur Radiol 2013;23:797-804. [Crossref] [PubMed]
  70. Garcia-Murillas I, Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med 2015;7:302ra133. [Crossref] [PubMed]
  71. Olsson E, Winter C, George A, et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med 2015;7:1034-47. [Crossref] [PubMed]
  72. Dawson SJ, Tsui DWY, Murtaza M, et al. Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer. N Engl J Med 2013;368:1199-209. [Crossref] [PubMed]
  73. Ma F, Zhu W, Guan Y, et al. ctDNA dynamics: anovel indicator to track resistance in metastatic breast cance rtreated with anti-HER2 therapy. Oncotarget 2016;7:66020-31. [Crossref] [PubMed]
  74. Spolverato G, Vitale A, Bagante F, et al. Liver Resection for Breast Cancer Liver Metastases: A Cost-utility Analysis. Ann Surg 2017;265:792-9. [Crossref] [PubMed]
  75. Grimaldi AM, Simeone E, Giannarelli D, et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology 2014;3:e28780. [Crossref] [PubMed]
  76. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med 2017;377:1919-29. [Crossref] [PubMed]
  77. Ng J, Dai T. Radiation therapy and the abscopal effect: a concept comes of age. Ann Transl Med 2016;4:118. [Crossref] [PubMed]
  78. Slovak R, Ludwig JM, Gettinger SN, et al. Immuno-thermal ablations - boosting the anticancer immune response. J Immunother Cancer 2017;5:78. [Crossref] [PubMed]
  79. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366:925-31. [Crossref] [PubMed]
  80. Ito F, Ku AW, Bucsek MJ, et al. Immune adjuvant activity of pre-resectional radiofrequency ablation protects against local and systemic recurrence in aggressive murine colorectal cancer. PLoS One 2015;10:e0143370. [Crossref] [PubMed]
Cite this article as: Terata K, Imai K, Wakita A, Sato Y, Motoyama S, Minamiya Y. Surgical therapy for breast cancer liver metastases. Transl Cancer Res 2020;9(8):5053-5062. doi: 10.21037/tcr-20-1598