Treating Breast Cancer That Has Spread to the Liver: A Complete Guide to Surgery and Radiofrequency Ablation

Table of Contents

• Key Points
• Why This Research Matters: Breast Cancer and Liver Metastases
• How This Study Was Conducted
• Key Findings: Surgical Removal of Liver Metastases
• Factors That Predict Better Outcomes After Surgery
• Oligometastases: When Cancer Spread Is Limited
• Surgery vs. Systemic Therapy Alone: What the Comparisons Show
• Repeat Liver Surgery for Recurrent Metastases
• Safety of Liver Surgery: Mortality and Complications
• Radiofrequency Ablation (RFA): A Less Invasive Option
• Cost-Effectiveness: Is Liver Surgery Worth It?
• Limitations of This Review
• What This Means for Patients
• Recommendations for Patients and Families
• Frequently Asked Questions
• Source Information

Key Points

• About 20%–30% of breast cancer patients eventually develop metastatic disease; the liver is the first site in 5%–20%.
• In 11 studies of 605 patients, liver resection achieved median overall survival of 39.5 months and 5-year survival of 38%.
• Favorable surgery outcomes included hormone receptor-positive tumors, clear margins, solitary small lesions, and no extrahepatic disease.
• Postoperative mortality was 0%–5%, median complications 28%, and median hospital stay 8.5 days.
• RFA offered median survival of 32 months with a 2-day hospital stay, often for patients with smaller tumors but more extrahepatic disease.

Why This Research Matters: Breast Cancer and Liver Metastases

Breast cancer is the most frequently diagnosed cancer in women around the world. In Japan alone, 76,257 new cases were diagnosed in 2014, according to the Cancer Information Service at the National Cancer Center of Japan. In the United States, 266,120 new cases were diagnosed in 2018, with 40,920 deaths from the disease that same year.

Estimates suggest that 20% to 30% of all breast cancer patients will eventually develop metastatic disease—meaning the cancer spreads to distant organs. The most common sites for breast cancer to spread are the bones (41.1%), lungs (22.4%), liver (7.3%), and brain (7.3%). While the liver is not the most common first site of spread, liver metastases (called breast cancer liver metastases, or BCLM) are the first site of metastatic disease in 5% to 20% of patients. Even more striking, half of all breast cancer patients will develop liver metastases at some point during their illness.

Metastatic breast cancer has long been considered incurable. Ten-year overall survival for patients receiving systemic therapy (medications that travel through the bloodstream) is only about 5%, and just 2% to 3% of patients maintain a complete response for more than 20 years. However, treatment has improved dramatically since the 1990s, when chemotherapy began extending the lives of metastatic breast cancer patients. Since the 2000s, newer "molecularly targeted" drugs have emerged, including:

• Anti-HER2 agents such as trastuzumab, pertuzumab, and T-DM1
• mTOR inhibitors and CDK4/6 inhibitor combined hormonal therapy
• Immune checkpoint inhibitors (ICIs), such as the anti-PD-L1 antibody atezolizumab
• PARP inhibitors, which are effective in BRCA-positive, HER2-negative metastatic breast cancers

Liver metastases have historically been viewed as incurable, with treatment being palliative—aimed at improving quality of life and prolonging survival rather than curing the disease. Surgery for liver metastases was long considered "too aggressive" for many breast cancer patients, partly because so many systemic therapy options exist. But growing evidence now suggests that surgery and other local treatments may offer a survival benefit for the right patients.

This review article set out to examine the indications for and outcomes of surgical liver resection and other local therapies for BCLM, synthesizing the best available evidence from studies published between 2000 and the present.

How This Study Was Conducted

The research team, based at Akita University Hospital and Akita University Graduate School of Medicine in Japan, searched the PubMed database using the terms "breast cancer," "liver metastases," and "surgery." Because major advances in drug therapy and surgical techniques occurred after 2000, they focused on major studies published after 2010, covering the two-decade period from 2000 to the present.

The review is divided into two main parts. The first part covers 11 articles (605 patients) focusing on surgical resection of liver metastases. The second part covers 7 articles describing radiofrequency ablation (RFA)—a technique that uses heat to destroy tumor tissue. The authors carefully analyzed each study's patient characteristics, surgical details, survival statistics, and complications.

Key Findings: Surgical Removal of Liver Metastases

The 11 surgical studies were published between 2012 and 2018 and included a median of 43 patients per study (ranging from 12 to 131 patients). Most studies were prospective (6 of 11), while 2 were retrospective and 3 were case-control studies. Nine studies analyzed patients from a single medical center, while two were multicenter analyses. In nearly all series, the study period began around or after 2000, although two large series (each with more than 100 patients) began in the 1980s.

Patient and Tumor Characteristics

Most patients had invasive ductal carcinoma, the most common form of breast cancer, accounting for a median 83% of cases (ranging from 12% to 92% across studies). Using the TNM staging system (which describes tumor size, lymph node involvement, and distant spread):

• A median of 83% of patients had T1 or T2 primary tumors (smaller tumors) at initial diagnosis
• Approximately half of all patients (52.5%; range 28–71%) had lymph node involvement at their original breast cancer diagnosis
• Distant metastases at the time of primary diagnosis were reported in only three studies, with rates of 0%, 10%, and 32%

Hormone receptor status was crucial. The median rate of estrogen receptor (ER) positivity was 75% (range 45–82%), and progesterone receptor (PR) positivity was 55% (range 9–82%). HER2 receptor status was positive in 39% of patients (range 14–55%). These percentages matter because they indicate which targeted hormonal therapies might work.

Survival Outcomes After Liver Resection

The surgery results were encouraging. The median time from initial breast cancer diagnosis to the diagnosis of liver metastases was 34 months (range 20–60 months). The median maximum tumor size was 4 cm (range 1.8–5.2 cm), and the median rate of extrahepatic metastases (cancer outside the liver, or EHM) was 26.5% (range 7–45%).

Surgeons performed major resection (removing three or more liver segments) in 47% of patients (259 out of 556). Complete removal with microscopically negative margins (R0 resection)—meaning no cancer cells visible at the edge of the removed tissue under a microscope—was achieved at a median rate of 86% (range 53–92%). The overall recurrence rate was 42.5% (153 out of 360 patients), with a median of 40%.

Patients were followed for a median of 55 months (range 22–69 months). The key survival numbers were:

• Median disease-free survival (DFS): 23 months (range 14–29 months)
• Median overall survival (OS): 39.5 months (range 26–82 months)
• 1-year overall survival: 89.5% (range 80–100%)
• 3-year overall survival: 70% (range 46–81%)
• 5-year overall survival: 38% (range 11–69%)

The authors caution that these studies had different numbers of patients, different clinical features, and different study designs, so the data must be interpreted carefully. Notably, six of the 11 studies described systemic therapy given alongside surgery, including hormone therapy with or without chemotherapy (doxorubicin, taxol, capecitabine, gemcitabine) and/or trastuzumab or lapatinib. None of the patients in these studies had received the newer targeted therapies such as pertuzumab, CDK4/6 inhibitors, or immune checkpoint inhibitors—meaning current survival rates might be even better.

Factors That Predict Better Outcomes After Surgery

Not every patient benefits equally from liver surgery. The authors identified independent factors that strongly influenced survival after liver resection for BCLM:

• Hormone receptor-positive primary breast cancer: Seven studies (three multivariate and four univariate analyses) found that patients whose original breast cancer was hormone receptor-positive had better overall survival after liver surgery. This suggests that hormone-driven tumors may respond better to combined hormonal and surgical treatment.
• R0 resection (clear margins): Four studies found that complete removal of the liver metastasis with no cancer cells at the margin was associated with better overall survival.
• No extrahepatic metastases (EHM): Three multivariate analyses showed that having cancer outside the liver at the time of surgery was linked to poorer overall survival.
• Smaller tumor size: Liver metastases smaller than 3 cm were associated with better overall survival, while tumors 3.5 cm or larger were associated with poorer progression-free survival. Tumor size was also linked to outcomes in univariate analyses.
• Solitary liver metastases: Patients with a single liver lesion had better overall survival, and the number of metastases was associated with both disease-free survival and overall survival.
• Longer disease-free interval: Patients who had a disease-free interval of 4 years or less before liver metastases appeared had poorer overall survival and progression-free survival. A disease-free interval of less than 2 years was also linked to poorer overall survival in univariate analysis.
• Response to pre-operative systemic therapy: Patients who responded to chemotherapy before surgery did much better. In the study by Abbott and colleagues, patients with a partial response to chemotherapy had a median survival of nearly 80 months, compared with approximately 30 months for patients with less than a partial response.

Other primary tumor characteristics—including T stage (tumor size at original diagnosis), lymph node metastases, and tumor grade—also influenced overall survival. The table below summarizes which factors predicted positive outcomes in each major study.

• Abbott: Hormone receptor-positive primary tumor, pre-operative stable disease, and disease-free interval over 2 years
• Dittmar: R0 resection, no extrahepatic metastases, HER2 expression, age under 50 years, and BCLM under 5 cm
• Mariani: Bone-only extrahepatic disease and lower N stage (primary)
• Kostov: Hormone receptor-positive primary, R0 resection, BCLM under 4 cm, response to non-surgical treatment, negative portal lymph nodes
• Polistina: Hormone receptor-positive primary, fewer than 3 metastases
• Treska: Hormone receptor-positive primary, BCLM under 3.5 cm, no extrahepatic disease, age over 50 years, disease-free interval over 4 years
• Bacalbasa: Hormone receptor-positive primary, BCLM under 5 cm, fewer metastases, lower N stage
• Weinrich: Low-grade primary tumor, R0 resection, fewer metastases, lower T and N stage
• Ruiz (2015): Fewer metastases, hormone receptor-positive primary, disease-free interval over 2 years
• Margonis: R0 resection, BCLM under 3 cm

Oligometastases: When Cancer Spread Is Limited

A particularly important concept highlighted in this review is oligometastatic disease. According to the 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4), 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, surgical removal of liver metastases is a well-established, standard treatment. However, this strategy remains more controversial for breast cancer liver metastases—even when the disease is oligometastatic.

The authors note that more than 50% of patients in the reviewed studies had solitary liver metastases. This is encouraging, because several studies found that solitary tumors were associated with better outcomes. Dittmar and colleagues observed that significantly more long-term survivors—those surviving 60 months or more—had solitary tumors. Weinrich's study of isolated liver metastasis resection found that 16 of 29 female patients (55%) had exactly one BCLM and 6 (21%) had two.

The 1-year survival rate in Weinrich's study was 86% for patients who underwent resection versus only 37.5% for those who did not. R0 resection, fewer liver metastases, and a longer time interval between breast cancer diagnosis and liver metastasis diagnosis were all significant prognostic factors.

Surgery vs. Systemic Therapy Alone: What the Comparisons Show

No prospective randomized trials have yet examined resection of BCLM. However, several case-control studies have compared patients who received surgery plus systemic therapy against matched patients who received systemic therapy alone. These studies provide the strongest available evidence that surgery helps.

Mariani study (2013): This study matched 51 patients with BCLM who underwent surgery to 51 patients receiving systemic treatment only. Patients were matched for age, year of breast cancer diagnosis, time to metastasis, TNM stage, hormone receptor status, and tumor pathology. None had more than 4 BCLM, and most had fewer than 4. The results showed:

• 3-year survival for surgically treated patients: 80.7%
• 3-year survival for non-surgically treated patients: 50.9%
• The difference was highly statistically significant (P<0.0001)

Ruiz study (2018): This European case-matched study used propensity score matching to compare patients receiving systemic therapy plus liver resection with those receiving systemic therapy alone. Matching was based on age, decade of diagnosis, time to metastases, maximum size of metastases, single versus multiple tumors, chemotherapy, and hormonal or targeted therapy after diagnosis. The results were dramatic:

• Median overall survival: 82 months with surgery versus 31 months without (P<0.001)—more than twice as long
• 3-year overall survival: 81% versus 69%
• 5-year overall survival: 33% versus 24%
• Patients who had systemic therapy plus liver resection were significantly less likely to die, with a hazard ratio of 0.28 (95% confidence interval: 0.15–0.52; P<0.001)—meaning a 72% lower risk of death during the study period

Sadot study: This case-control study compared 167 patients with isolated BCLM. Sixty-nine patients received surgery and/or ablation, while 98 received medical treatment only, with a median follow-up of 73 months. The surgical group tended to have estrogen receptor-positive tumors and were more likely to receive adjuvant chemotherapy and radiotherapy for their primary breast tumor. Their hepatic tumor volume was smaller, and their time to diagnosis of BCLM was significantly longer (53 vs. 30 months). Interestingly, this study found no significant difference in overall survival between the surgical and systemic therapy groups:

• Median overall survival: 50 versus 45 months
• 5-year overall survival: 38% versus 39%

However, even in this study, the surgical group had a median recurrence-free interval of 28.5 months, and 10 patients (15%) were recurrence-free after 5 years. The authors of this review conclude that surgical treatment of BCLM may be applicable in carefully selected patients—particularly those in whom the goal is to minimize or avoid systemic chemotherapy.

Repeat Liver Surgery for Recurrent Metastases

Some patients develop new liver metastases after their first surgery. Ruiz and colleagues reported on a series of patients undergoing "repeat hepatectomy" (a second liver surgery). They compared the single hepatectomy group (120 patients) with those who underwent repeat hepatectomy (19 patients). The proportion of patients with solitary liver metastases was 39% in the single-surgery group and 53% in the repeat-surgery group.

Surprisingly, patients who received a repeat hepatectomy had longer survival than those who had undergone only a single hepatectomy:

• 3-year survival: 95% versus 50%
• 5-year survival: 84% versus 38% (P=0.002)
• Median survival: 100 months versus 35 months

The number of metastatic tumors also mattered. Patients with a solitary BCLM at their first hepatectomy had 3-year and 5-year overall survival rates of 76% and 76%, compared with only 51% and 17% for patients with multiple metastases (P=0.023).

Factors that predicted better outcomes after repeat hepatectomy included a time interval of more than 2 years between breast cancer diagnosis and the first liver surgery, a limited hepatectomy, solitary metastases, positive progesterone receptor status, and chemotherapy following the repeat surgery. The authors suggest that repeat hepatectomy is potentially curative when combined with systemic therapy.

Safety of Liver Surgery: Mortality and Complications

Surgery for liver metastases is a major operation, so patients naturally want to know about risks. The news here is reassuring. In the reviewed studies:

• Postoperative mortality (death within 30 days of surgery) was 0% in five reports, 2% in one report, and 5% in one report
• Median postoperative morbidity (complication rate) was 28% (range 18–42%)
• Major complications developed in 3.5% to 12% of cases

Major complications included multiple organ failure, biliary leakage (bile leaking from the liver), biliary fistula, infected fluid collections in the abdomen requiring drainage, and conditions requiring percutaneous drainage procedures. The median hospital stay was 8.5 days (range 6–11 days), with individual study averages ranging from 6 to 11 days.

Radiofrequency Ablation (RFA): A Less Invasive Option

Not every patient is a candidate for surgery. For those with smaller tumors or more extensive disease elsewhere, radiofrequency ablation (RFA)—which uses heat generated by high-frequency electrical currents to destroy tumor cells—offers a less invasive alternative. The review also mentions other local treatments including cryoablation (CRA, freezing), stereotactic radiofrequency ablation (SRFA), brachytherapy (internal radiation), and transarterial chemoembolization (TACE).

The RFA portion of this review covers 7 reports totaling 225 patients in the detailed analysis (the abstract cites 266 patients), published from 2007 to 2018. These studies were conducted during the period from 1996 to 2015. Key characteristics included:

• Median number of patients per study: 43 (range 12–69)
• Median number of treated tumors per study: 87 (range 13–135)
• Average number of tumors per patient: 1.9 (range 1.1–2.1)
• Mean size of metastases: 2.4 cm (range 2–3.5 cm)—smaller than the 4 cm average for surgical patients
• Average rate of extrahepatic metastases: 36% (with wide variation across studies)—higher than the 27% typical for surgical candidates
• Median complete response rate: 86% (range 67–97%)
• Median rate of solitary BCLM: 55.5% (range 26–62%)

Two series used computed tomography (CT)-guided RFA, while five used conventional ultrasound-guided RFA. The survival outcomes were as follows:

• Median follow-up: 24 months
• Median disease-free survival: 11 months—shorter than the 23 months seen with surgery
• Median overall survival: 32 months
• 3-year overall survival: 43%
• 5-year overall survival: 27%

These numbers are lower than those for surgery, but it is essential to understand that RFA patients generally had different clinical features: smaller tumors but higher rates of extrahepatic metastases (46% vs. 27% in the abstract's comparison). In other words, RFA is often chosen for patients who are not ideal surgical candidates, which helps explain the different survival rates.

RFA Safety and Repeat Treatments

RFA's advantages include its high technical success rate, low complication rate, short hospital stay, and the ability to repeat it if needed. In four studies, the major complication rate was 0%. In the other three studies, major complication rates were 1.1%, 2.3%, and 6.9%—with complications including severe intrahepatic bleeding, bile duct injury, thrombosis (clotting) of the portal vein branch, sepsis, and cholecystitis (gallbladder inflammation). The median hospitalization period was just 2 days (range 1–5 days), much shorter than the 8.5 days for surgery.

RFA can be repeated when new tumors appear. Notable reports included:

• Sofocleous and colleagues described a patient who underwent three RFA sessions and achieved local control for 47 months
• Jakobs and colleagues observed local tumor progression in 15 of 111 metastases at 3 months of follow-up; 5 patients received repeat RFA
• Meloni and colleagues reported that a BCLM exceeding 2.5 cm in size was related to poor outcomes—underscoring the importance of treating tumors early while they are small
• Bai and colleagues reported on 69 patients with 135 liver metastases. Local tumor progression was seen in 8 patients, 4–8 months after RFA. The ablation margin—the healthy tissue border around the tumor—was critical: progression rates for margins of 0–5 mm, greater than 5–10 mm, and greater than 10 mm were 38.9%, 3.6%, and 0%, respectively. Among the 8 patients with progression, 7 required repeat RFA.

This "margin" finding is one of the most actionable messages from the RFA data: achieving a wider margin of destruction around the tumor dramatically reduces the chance of the tumor coming back. It also shows a promising future direction: combining RFA with immune checkpoint inhibitors may enhance the body's antitumor immunity. Just as radiotherapy can trigger a "distal antitumor response" (the abscopal effect, where treating one tumor causes others elsewhere to shrink), RFA combined with immunotherapy may prime the immune system to attack cancer throughout the body.

Cost-Effectiveness: Is Liver Surgery Worth It?

The authors also address the important question of cost. Spolverato and colleagues evaluated the cost-effectiveness of liver resection using a Markov model and Monte-Carlo simulation. They compared three treatment strategies: liver resection followed by postoperative conventional systemic therapy, conventional therapy alone, and newer targeted therapy alone.

The conclusion was that liver resection is potentially more cost-effective than systemic therapy alone, especially in patients who are estrogen receptor-positive and/or those receiving newer systemic therapies. The authors of this review note that these cost data add to the broader discussion of how best to treat patients with BCLM.

Limitations of This Review

It is important to understand what this review could and could not prove. The studies analyzed were not randomized controlled trials—the gold standard of medical evidence. Instead, they were largely retrospective or prospective observational studies and case-control studies. This means that the apparent survival benefits of surgery might partly reflect patient selection: healthier patients with smaller, fewer, and slower-growing

Frequently Asked Questions

What are breast cancer liver metastases?

Breast cancer liver metastases (BCLM) are cancer cells from a breast tumor that have spread to the liver. They are the first site of spread in 5%–20% of patients, and about half of all breast cancer patients develop liver metastases at some point. The liver is less common than bone or lung as a first site.

What is radiofrequency ablation (RFA) and how does it compare with surgery?

RFA uses heat to destroy liver tumors and is less invasive than surgery. In 7 studies, median overall survival was 32 months, and hospital stay was about 2 days. RFA patients typically had smaller tumors but more extrahepatic disease, which may explain lower survival rates.

Can liver surgery be repeated if metastases come back?

Yes. In one study, patients who had a repeat hepatectomy for recurrent liver metastases had a median survival of 100 months, compared with 35 months for those who had only one surgery. Three-year survival was 95% versus 50%. Solitary lesions and longer intervals before first surgery predicted better results.

Which factors predict better outcomes after liver surgery?

Better outcomes were linked to hormone receptor-positive primary tumors, complete removal with clear margins (R0), solitary small liver lesions (under 3 cm), no extrahepatic metastases, a disease-free interval longer than 2–4 years, and a response to pre-operative systemic therapy. These factors were identified across multiple studies.