Liver Surgery for Breast Cancer That Has Spread to the Liver: What the Latest Research Shows

Table of Contents

• Key Points
• Understanding the Problem: Breast Cancer and Liver Metastases
• Why Is There Uncertainty About Liver Surgery?
• How This Research Was Conducted
• The 9 Studies Included in This Analysis
• Key Finding: Survival at 1 Year
• Key Finding: Survival at 3 Years
• Key Finding: Survival at 5 Years
• Overall Survival: The Big Picture
• What This Means for Patients
• Study Limitations
• Recommendations
• Frequently Asked Questions
• Source Information

Key Points

• A meta-analysis of 9 studies with 1,732 patients found liver resection improved overall survival in breast cancer liver metastases.
• Surgery was associated with a 31% lower risk of death over time compared with no surgery.
• Five-year survival was 46.0% with surgery versus 24.7% without surgery in this analysis.
• Benefits were seen in carefully selected patients, such as those with limited liver involvement and no extrahepatic disease.
• Randomized trials are still needed; this study does not prove surgery is superior for all patients.

Understanding the Problem: Breast Cancer and Liver Metastases

Breast cancer is the most common cancer in women worldwide, with 2.3 million new diagnoses made in 2020 alone. Thanks to improvements in early detection, personalized treatments, and better therapeutic strategies, many patients now have excellent outcomes — some can expect 5-year overall survival rates as high as 90%.

Yet breast cancer remains a serious threat. In 2021, more than 43,000 patients in the United States were expected to die from breast cancer. About 6–10% of patients already have metastatic disease (cancer that has spread to other organs) at the time of their initial diagnosis, and another 20–30% of patients diagnosed with early-stage disease will eventually develop distant metastases.

The liver is one of the most common sites where breast cancer spreads. In fact, the liver is the first site of distant metastasis in 1.0–8.0% of breast cancer cases. Historically, breast cancer with liver metastases (BCLM) has been associated with poor outcomes — the estimated 5-year overall survival rate after the cancer recurs in the liver is only 8.5%.

It's important to understand what "metastatic" means: when breast cancer cells travel through the bloodstream or lymphatic system to settle in another organ like the liver, the disease is considered stage 4 (metastatic) breast cancer. While it is not typically considered curable in the traditional sense, some patients can live for many years with modern treatments.

Why Is There Uncertainty About Liver Surgery?

Surgery to remove liver metastases has proven highly effective for another type of cancer: colorectal cancer (CRC). In patients with CRC that has spread to the liver, liver resection (also called hepatectomy) can be curative, and it is now recommended in the European Society for Medical Oncology (ESMO) guidelines whenever feasible.

But for breast cancer that has spread to the liver, there is no widely accepted consensus on surgery. Major guideline groups have taken different positions:

• The 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC4) state that local therapy (such as surgery) should only be proposed in very selected cases — specifically for patients with good performance status, limited liver involvement (no cancer outside the liver), and demonstrated control of disease after adequate systemic therapy.
• The National Comprehensive Cancer Network (NCCN) guidelines, widely used in the United States, do not recommend liver resection as an option for curative treatment of BCLM.

Only about 1.8% of all liver resections performed are for breast cancer secondaries — a reflection of the medical community's hesitation. A major reason for this hesitation is that fewer than 8.0% of patients with metastatic breast cancer have disease confined only to the liver. If cancer has spread elsewhere in the body, removing just the liver tumors may seem less helpful.

This uncertainty means doctors lack clear guidance on which patients, if any, might truly benefit from liver surgery. The current study was designed to address this gap.

How This Research Was Conducted

The researchers performed a systematic review and meta-analysis — a type of study that combines results from multiple existing studies to reach stronger conclusions than any single study alone. They followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE guidelines, which are internationally recognized standards for conducting this type of research.

The PICO framework was used to define the research question:

• Population: Female patients aged 18 years or older with newly diagnosed breast cancer with liver metastases (BCLM), confirmed by histology or radiology.
• Intervention: Surgical resection (removal) of the liver metastasis with curative intent.
• Comparison: Patients treated for BCLM without surgical resection of the liver metastasis.
• Outcomes: Annual survival after BCLM diagnosis — specifically overall survival at 1, 3, and 5 years, as well as overall survival expressed as hazard ratios (HR).

An electronic search was performed across three major medical databases: PubMed Medline, EMBASE, and Scopus. Two independent reviewers conducted the search using terms such as "breast liver metastases," "breast liver metastases resection," "hepatic metastases," "breast cancer survival," "breast cancer," and "hepatectomy." Only English-language studies were included, and the search was not restricted by year of publication. However, only studies published since 2013 were included in the meta-analysis, because targeted therapies have revolutionized breast cancer management in recent years.

The final search was performed on July 7, 2021. The initial search identified 2,618 studies. After removing 118 duplicates and 9 non-English papers, and screening titles, abstracts, and full texts, 9 studies meeting all inclusion criteria remained. These 9 studies were the focus of the meta-analysis.

For statistical analysis, survival data were expressed as odds ratios (OR) using the Mantel-Haenszel method. A hazard ratio (HR) — which measures how quickly death occurs over time — was calculated using the generic inverse variance method. All tests were two-tailed, with P values less than 0.050 considered statistically significant. Study quality was assessed using the Newcastle-Ottawa Scale.

The 9 Studies Included in This Analysis

The 9 studies included data from 1,732 patients in total. Of these, 24.5% (424 patients) underwent surgical resection of their liver metastases, while 75.5% (1,308 patients) did not. Three of the 9 studies (33.3%) were prospective in design (following patients forward in time), while the remaining 6 (66.7%) were retrospective (looking back at medical records). Publication dates ranged from 2013 to 2020.

The studies came from around the world, including Italy, the United Kingdom, China, the United States, France, Germany, and the Czech Republic. All patients were female, with a mean age at diagnosis of 52.9 years (range 25–94 years). There were 369 patients with synchronous disease (21.3%), meaning liver metastases were discovered within 6 months of the primary breast cancer diagnosis.

Here is the breakdown of the individual studies:

Information on tumor type and hormone receptor status was available from several studies. Among those reporting this data, 285 patients had ductal carcinoma, 24 had lobular carcinoma, and 9 had other subtypes. Hormone receptor status was recorded as follows: 130 were estrogen receptor positive (ER+), 83 were progesterone receptor positive (PR+), and 66 were HER2 positive (HER2+).

Key Finding: Survival at 1 Year

One year after diagnosis of liver metastases, patients who underwent surgery had significantly better overall survival than those who did not. In the surgery group, 92.5% (124 of 134 patients) were alive at 1 year, compared to 79.7% (311 of 390 patients) in the non-surgery group (P < 0.001).

Looked at another way, the mortality rate (death rate) at 1 year was 7.5% (10 of 134) for surgical patients versus 20.3% (79 of 390) for non-surgical patients. When the results were pooled using meta-analysis, the odds of death were dramatically lower for the surgery group (OR: 0.25, 95% CI: 0.08–0.74, P = 0.010). An odds ratio of 0.25 means the odds of dying within 1 year were 75% lower in the surgery group compared to the non-surgery group.

Statistical heterogeneity between studies at this time point was low (I² = 32%), meaning the studies were reasonably consistent with each other, which strengthens confidence in this finding. Of note, one large study (Feng 2020) contributed 81.8% of the non-surgical patients at this time point.

Key Finding: Survival at 3 Years

At 3 years after diagnosis of BCLM, the survival gap between the two groups was even more pronounced. Among patients who underwent liver resection, 81.9% (123 of 152) were still alive, compared to just 47.0% (197 of 419) in the non-surgery group (P < 0.001).

The mortality rates tell the same story: 19.1% (29 of 152) of surgical patients had died by 3 years, versus 53.0% (222 of 419) of non-surgical patients. When the investigators pooled the data at the meta-analysis level, however, the difference did not reach statistical significance — the odds ratio was 0.32 (95% CI: 0.09–1.12, P = 0.070).

This means that while individual studies showed a clear advantage for surgery, the combined statistical analysis could not definitively prove that surgery reduced 3-year mortality. There was substantial heterogeneity between studies at this time point (I² = 77%), meaning the studies differed considerably from each other — likely due to differences in patient populations, treatments, and study designs. One study (Feng 2020) accounted for 76.1% of the non-surgical patients at this time point.

Key Finding: Survival at 5 Years

Perhaps the most striking finding emerged at 5 years after diagnosis. Among patients who had liver resection, 46.0% (162 of 352) were alive at 5 years, compared to only 24.7% (309 of 1,249) in the non-surgery group (P < 0.001).

In terms of mortality, 54.0% (190 of 352) of surgical patients had died by 5 years, versus 75.3% (940 of 1,249) of non-surgical patients. The pooled meta-analysis confirmed a statistically significant survival benefit for surgery (OR: 0.46, 95% CI: 0.25–0.87, P = 0.020) — meaning the odds of death at 5 years were 54% lower for those who underwent resection. Heterogeneity was moderate to high (I² = 70%).

The two largest studies — Feng 2020 and Chun 2020 — together accounted for 86.6% of the non-surgical patients at 5 years, meaning the results are heavily weighted toward the findings of these two well-conducted analyses.

Looking at the individual studies at 5 years:

• Feng 2020: 58.5% surgery survival vs. 27.9% non-surgery survival
• Chun 2020: 52.9% vs. 21.0%
• Abbas 2017: 52.2% vs. 47.4%
• Sadot 2016: 37.7% vs. 38.8% (the only study showing no difference)
• Polistina 2013: 33.3% vs. 14.3%
• Dittmar 2013: 26.5% vs. 16.7%
• Treska 2014: 7.7% vs. 9.1%

Overall Survival: The Big Picture

When the researchers combined all survival data over the entire follow-up period (mean follow-up of 37 months), patients who underwent surgery had significantly better overall survival than those who did not. The pooled hazard ratio was 0.69 (95% CI: 0.59–0.80, P < 0.00001), with low heterogeneity between studies (I² = 21%).

What does a hazard ratio of 0.69 mean for patients? It means that at any given point during the follow-up period, patients who had liver resection were 31% less likely to die than those who did not have surgery. This is a clinically meaningful benefit — a substantial reduction in the risk of death over time.

It's important to understand, however, that this benefit is not universal. The 5-year survival rate of only 24.7% in the non-surgery group reflects what might be expected with systemic therapy alone in this patient population. Notably, the authors point out that in today's era of modern targeted treatments, patients with estrogen receptor (ER)-positive or HER2-positive metastatic disease can often expect their median survival to reach or even exceed 5 years. This suggests that the 24.7% 5-year survival in the control group may be lower than what some patients could achieve with modern systemic therapy — and underscores that the survival benefit of surgery needs to be weighed against the effectiveness of contemporary drug treatments.

What This Means for Patients

So what does this research mean for a patient facing a diagnosis of breast cancer that has spread to the liver? The findings suggest that surgical removal of liver metastases may offer a realistic chance of long-term survival for carefully selected patients.

Based on this and other research, the following factors appear to identify patients who may benefit most from liver resection:

• Negative axillary lymph nodes at the time of breast surgery
• Solitary liver lesions (fewer tumors in the liver)
• More than 24 months between the original breast cancer diagnosis and the appearance of liver metastases
• R0 hepatic resection — meaning the surgeon was able to remove the tumor completely with clear margins (no cancer cells left at the edge of the removed tissue)
• No extrahepatic disease — cancer that has not spread beyond the liver is associated with better outcomes

On the flip side, patients with triple-negative breast cancer appear to have poorer survival outcomes after surgery for BCLM, and higher numbers of metastatic lesions and younger age have also been associated with poorer outcomes. The authors note that extrahepatic disease is the single most important negative prognostic factor — one study of 34 patients found it was the only factor associated with reduced survival.

The authors also highlight a key point about the control group: in this analysis, the 5-year overall survival for patients treated with systemic therapy alone was only 24.7%. This is an important context for treatment decisions, but it's also worth knowing that modern targeted therapies have improved outcomes, and some patients with ER+ or HER2+ disease will do much better than this historical average.

Study Limitations

Every study has limitations, and the authors are transparent about theirs. Here are the most important ones to keep in mind:

• No randomized controlled trials. None of the 9 included studies were randomized, meaning patients were not randomly assigned to surgery or no surgery. This introduces the risk of selection bias — the possibility that patients who had surgery were healthier or had less aggressive disease to begin with, which could partly explain their better survival. The quality assessment confirmed a performance bias in all included studies.
• Heterogeneity between studies. There was significant variability between studies in terms of patient populations, treatment approaches, and study designs. This is reflected in the moderate-to-high I² values at the 3-year and 5-year time points.
• Varied treatment strategies. The chemotherapy, hormonal therapy, and other treatments patients received varied across studies, and not all details were available. Some surgical patients received (neo)adjuvant chemotherapy and endocrine therapy; others had surgery alone.
• Missing clinicopathological data. There was no data available to compare how patient age, gender, comorbidities, or hormone receptor status affected outcomes.
• No data on recurrence or quality of life. Limited data was available on cancer recurrence after liver resection, and the cost-effectiveness of aggressive treatment strategies and their impact on quality of life were not addressed. The chance of achieving complete disease control is reported to be low in previous studies, and recovery from aggressive surgery can significantly impact quality of life.

It's also important to note that there are currently no registered clinical trials exploring surgical resection of BCLM, which means prospective, randomized data is still missing from the evidence base.

Recommendations

Based on the findings of this meta-analysis, the authors offer the following guidance:

1. Liver resection should be considered at multidisciplinary team (MDT) meetings for patients with breast cancer liver metastases. A multidisciplinary approach — involving surgeons, medical oncologists, radiation oncologists, radiologists, and pathologists working together — is essential to weigh the potential benefits and risks for each individual patient.
2. Judicious patient selection is crucial. Surgery should not be offered to everyone, but rather to those who have the features associated with better outcomes — limited liver involvement, no (or stable) extrahepatic disease, good performance status, and disease that has responded to systemic therapy.
3. Patients should have honest conversations with their oncologists about whether liver surgery is appropriate for their specific situation, taking into account their tumor biology (hormone receptor and HER2 status), the extent of their disease, and their overall health.
4. Randomized prospective trials are urgently needed. The authors call for validation of these results in the next generation of prospective, randomized studies to better guide clinical decision-making and to clarify which patients benefit most.

The authors emphasize that this study does not prove the superiority of surgery as an intervention in BCLM. Rather, it demonstrates the pragmatic role of surgery in improving overall survival in carefully selected patients — a meaningful distinction for patients and clinicians to understand when making treatment decisions.

For patients, the key takeaway is hopeful but measured: liver resection for breast cancer metastases is a legitimate treatment option that may significantly extend life in the right circumstances. The decision should be personalized, made by an experienced multidisciplinary team, and based on a thorough evaluation of your specific cancer biology, overall health, and treatment goals.

Frequently Asked Questions

Who might be a candidate for liver surgery when breast cancer spreads to the liver?

Based on this research, patients who may benefit most have limited liver involvement, cancer that has not spread beyond the liver, good performance status, and disease controlled after systemic therapy. Other favorable features include negative axillary lymph nodes, a single liver lesion, and a long interval between breast cancer diagnosis and liver metastasis. Decisions should be made by a multidisciplinary team.

What does a hazard ratio of 0.69 mean for my survival?

A hazard ratio of 0.69 means that at any given point during the follow-up period, patients who had liver resection were 31% less likely to die than those who did not have surgery. This is a clinically meaningful reduction in the risk of death over time, though it does not guarantee individual outcomes.

What are the main limitations of this study on liver surgery for breast cancer metastases?

The authors note that none of the 9 included studies were randomized, so selection bias is possible. There was significant variation between studies, and details on chemotherapy and other treatments were incomplete. No data on recurrence or quality of life was available. They emphasize the need for randomized trials to confirm these results.

Why do doctors disagree about using liver surgery for breast cancer that has spread to the liver?

Guidelines differ: the ESO-ESMO consensus recommends surgery only in very selected cases, while NCCN guidelines do not list liver resection as a curative option. Also, fewer than 8% of patients with metastatic breast cancer have disease confined only to the liver, making it hard to know who benefits. This study aimed to address that gap.

What should I ask my doctor about liver surgery for breast cancer that spread to my liver?

Ask whether liver resection is an option for your specific situation. Discuss your tumor biology, hormone receptor and HER2 status, the extent of liver involvement, and whether cancer exists outside the liver. Also ask about your overall health and performance status, and how surgery would fit with systemic therapy. A multidisciplinary team should weigh benefits and risks.

Source Information

Original Article Title: impact of liver resection on survival for patients with metastatic breast cancer

Authors: Gavin G. Calpin, Matthew G. Davey, Pádraig Calpin, Ferdia Browne, Aoife J. Lowery, Michael J. Kerin

Journal: The Surgeon, Volume 21 (2023), pages 242–249

Publication Details: Received May 26, 2022; accepted October 13, 2022; available online November 1, 2022. Published by Elsevier Ltd on behalf of the Royal College of Surgeons of Edinburgh and the Royal College of Surgeons in Ireland. This is an open access article under the CC BY-NC-ND license.

Funding: This research received no external funding. All authors declared no conflicts of interest.

This patient-friendly article is based on peer-reviewed research. It is intended for informational purposes only and does not constitute medical advice. Patients should discuss their individual treatment options with their healthcare team.