{"product_id":"treating-breast-cancer-that-has-spread-to-the-liver-a-complete-guide-to-surgery-and-radiofrequency-ablation","title":"Treating Breast Cancer That Has Spread to the Liver: A Complete Guide to Surgery and Radiofrequency Ablation","description":"\u003cp\u003eThis review pooled 11 studies of liver surgery in 605 women with breast cancer that had spread to the liver. These are called breast cancer liver metastases, or BCLM. The review also pooled 7 studies of radiofrequency ablation (RFA) in 225–266 patients. RFA is a heat-based technique that destroys tumors without surgery. After surgery, patients lived a median of 39.5 months, and 38% — about 4 in 10 — were alive at 5 years. RFA produced a shorter median survival of 32 months and a 5-year survival of 27%, but it is far less invasive, requires about 2 days in hospital, and can be repeated. The features linked to the best outcomes were hormone receptor–positive primary tumors. Other features were complete removal of all visible tumor (R0 resection), no cancer outside the liver, and small or solitary liver tumors.\u003c\/p\u003e\n\n\u003ch1\u003eSurgical therapy for breast cancer liver metastases\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow This Review Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#characteristics\"\u003eThe Patients and Their Tumors\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#resection-outcomes\"\u003eResults of Liver Surgery\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#prognostic-factors\"\u003eWhich Factors Predict a Better Outcome?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#oligometastases\"\u003eOligometastatic Disease and Repeat Surgery\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#case-control\"\u003eSurgery Plus Drug Therapy vs. Drug Therapy Alone\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#risks\"\u003eRisks, Complications, and Hospital Stay After Surgery\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#rfa\"\u003eRadiofrequency Ablation and Other Local Treatments\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#cost\"\u003eCost-Effectiveness of Liver Surgery\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#future\"\u003eFuture Directions: Combining Treatments\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What This Review Cannot Prove\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003ePractical Recommendations\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn pooled studies of 605 women, median survival after liver surgery for breast cancer metastases was 39.5 months, and 38% were alive at 5 years.\u003c\/li\u003e\n\u003cli\u003eRadiofrequency ablation produced a median survival of 32 months and 5-year survival of 27%, with about 2 days in hospital and lower complication rates.\u003c\/li\u003e\n\u003cli\u003eFavorable features included hormone receptor–positive primary tumors, complete removal (R0), no cancer outside the liver, and small or single liver tumors.\u003c\/li\u003e\n\u003cli\u003eNo randomized trial has compared liver surgery with drug therapy alone; patients chosen for surgery tend to be healthier, so results must be interpreted carefully.\u003c\/li\u003e\n\u003cli\u003ePostoperative death after liver surgery was 0% to 5%; complications occurred in about 28%, and the median hospital stay was 8.5 days.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eBreast cancer is the most frequently diagnosed cancer in women worldwide. In Japan, 76,257 breast cancer cases were diagnosed in 2014, according to the Cancer Information Service at the National Cancer Center of Japan. In the United States, 266,120 breast cancer cases were diagnosed in 2018, and 40,920 women died of the disease that year.\u003c\/p\u003e\n\n\u003cp\u003eWhen breast cancer is found early, patients generally do well. But roughly 20% to 30% of all women diagnosed with breast cancer — about 1 in 5 to 1 in 3 — develop metastatic disease (cancer that has spread to distant organs). The leading sites of distant spread are bone (41.1%), lung (22.4%), liver (7.3%), and brain (7.3%).\u003c\/p\u003e\n\n\u003cp\u003eThe liver is not the most common first site of spread, but it is an important one. BCLM (breast cancer liver metastases) is the first site of metastatic disease in 5% to 20% of patients. About half of all patients develop liver metastases at some point during their illness.\u003c\/p\u003e\n\n\u003cp\u003eMetastatic breast cancer, apart from local recurrence (cancer returning only at the original site), is considered incurable. Ten-year overall survival (OS, the proportion of patients still alive 10 years later) among patients given systemic therapy (drug treatment that travels through the bloodstream) is about 5%, roughly 1 in 20. Only 2% to 3% of patients stay in complete remission for more than 20 years.\u003c\/p\u003e\n\n\u003ch3\u003eDrug therapy has improved steadily\u003c\/h3\u003e\n\n\u003cp\u003eSystemic treatments have gotten better over time, and this has improved progression-free survival (PFS, time before the cancer grows again) and overall survival. Since the 1990s, chemotherapy has improved outcomes for patients with metastatic breast cancer. From the 2000s onward, newer options have appeared, including:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTargeted anti-HER2 agents\u003c\/strong\u003e (drugs that block a protein called human epidermal growth factor receptor type 2), such as trastuzumab, pertuzumab, and T-DM1\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003emTOR inhibitors\u003c\/strong\u003e (drugs that block a growth-signaling protein called mTOR)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCDK4\/6 inhibitors combined with hormonal therapy\u003c\/strong\u003e (drugs that interrupt how cancer cells divide)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eImmune checkpoint inhibitors\u003c\/strong\u003e (drugs that help the immune system attack cancer), such as atezolizumab, a humanized monoclonal anti-PD-L1 antibody\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePARP inhibitors\u003c\/strong\u003e for BRCA-positive, HER2-negative metastatic breast cancer\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eBecause so many drug options exist, surgery for liver metastases has long been viewed as too aggressive for many patients. Liver metastases were historically treated as incurable, with palliative care (treatment to relieve symptoms rather than cure) aimed at improving quality of life and prolonging survival.\u003c\/p\u003e\n\n\u003cp\u003eThat view is shifting. A growing body of evidence suggests that removing liver metastases, or destroying them with local therapies, may do two things. First, it can reveal important tissue information. That information is the tumor subtype, including estrogen receptor, progesterone receptor, and HER2 status of the metastatic tumor. Second, it may extend survival. Since 2000, many studies have examined surgical treatment of BCLM. Those studies tended to be small, and they used different criteria for choosing which patients had surgery. Still, some clinical benefits emerged. More recent results suggest that patients with solitary liver metastases or \"oligo-metastatic\" breast cancer (a small number of metastases) may benefit most from local therapies. This review examined the indications for and outcomes of liver resection and other local treatments for BCLM.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow This Review Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003eThe authors searched the PubMed database using the terms \"breast cancer,\" \"liver metastases,\" and \"surgery.\" Drug therapy has made major advances and surgical technique has improved. Because of these advances, the authors focused on major studies published after 2010. This means the review covers roughly the two decades from 2000 to the present.\u003c\/p\u003e\n\n\u003cp\u003eFor liver resection (surgery to remove part of the liver), the final analysis included \u003cstrong\u003e11 series totaling 605 patients\u003c\/strong\u003e. For radiofrequency ablation, the review covered \u003cstrong\u003e7 reports\u003c\/strong\u003e — described in the article's abstract as 266 patients and in the body of the text as 225 patients. The authors summarized primary tumor characteristics, clinical outcomes, and prognostic factors (factors that predict outcome) across these studies.\u003c\/p\u003e\n\n\u003ch2 id=\"characteristics\"\u003eThe Patients and Their Tumors\u003c\/h2\u003e\n\n\u003cp\u003eThe 11 surgical series were published between 2012 and 2018. In nearly all of them, the study period started around or after 2000, though two series began in the 1980s and each included more than 100 patients. The median (midpoint) number of patients per study was 43, with a range of 12 to 131.\u003c\/p\u003e\n\n\u003cp\u003eStudy designs varied. Six studies were prospective, meaning patients were followed forward in time. Two were retrospective, looking back at existing records. Three were case-control studies, comparing patients who had surgery with similar patients who did not. Nine were single-center analyses and two were multicenter analyses. Five series consisted of patients who had undergone radiofrequency ablation.\u003c\/p\u003e\n\n\u003ch3\u003ePrimary tumor features\u003c\/h3\u003e\n\n\u003cp\u003eThe most common tumor type was invasive ductal carcinoma, which made up a median of 83% of cases (range 12% to 92%).\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTumor stage (T) and lymph node stage (N)\u003c\/strong\u003e were reported in 7 series. A T1 or T2 primary tumor (relatively small, early-stage tumors) was present in a median of 83% of cases (range 54% to 92%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLymph node involvement:\u003c\/strong\u003e about half of the total patients (52.5%, range 28% to 71%) had cancer in their lymph nodes.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eM status\u003c\/strong\u003e (whether distant metastases were present when breast cancer was first diagnosed) was reported in only 3 series. The proportions of patients who already had distant metastases at the time of their original diagnosis were 0%, 10%, and 32%.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHormone receptor status\u003c\/strong\u003e was reported in 9 studies. Median estrogen receptor–positive rates were 75% (range 45% to 82%), and median progesterone receptor–positive rates were 55% (range 9% to 82%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHER2 status\u003c\/strong\u003e was reported in 7 studies. HER2 was positive in 39% of patients (range 14% to 55%) in those studies.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"resection-outcomes\"\u003eResults of Liver Surgery\u003c\/h2\u003e\n\n\u003cp\u003eThe numbers below come from heterogeneous studies in which selection bias is a weakness, and the authors call the effectiveness of local treatment, including liver surgery, for these liver metastases still controversial.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTime to developing liver metastases:\u003c\/strong\u003e a median of 34 months (range 20 to 60 months) across 8 studies.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLargest liver tumor size:\u003c\/strong\u003e a median of 4 cm (range 1.8 to 5.2 cm) across 8 reports.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCancer outside the liver (extrahepatic metastases, EHM):\u003c\/strong\u003e a median of 26.5% of patients (range 7% to 45%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMajor resection\u003c\/strong\u003e (removing three or more liver segments): performed in 47% of patients (259 of 556), with a median of 42.5% per study (range 29% to 69%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eComplete surgical removal (R0 resection, meaning no cancer cells visible at the cut edge under a microscope):\u003c\/strong\u003e reported in 9 studies, with a median of 86% (range 53% to 92%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCancer recurrence:\u003c\/strong\u003e 42.5% of patients (153 of 360) had the cancer return, with a median recurrence rate per study of 40% (range 14% to 52%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMedian follow-up:\u003c\/strong\u003e 55 months (range 22 to 69 months).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eSurvival after surgery\u003c\/h3\u003e\n\n\u003cp\u003eMedian disease-free survival (DFS, time alive without the cancer returning) was \u003cstrong\u003e23 months\u003c\/strong\u003e (range 14 to 29 months). Median overall survival was \u003cstrong\u003e39.5 months\u003c\/strong\u003e (range 26 to 82 months).\u003c\/p\u003e\n\n\u003cp\u003eSurvival at the standard checkpoints was:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e1 year:\u003c\/strong\u003e 89.5% (range 80% to 100%)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e3 years:\u003c\/strong\u003e 70% (range 46% to 81%)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e5 years:\u003c\/strong\u003e 38% (range 11% to 69%) — roughly 4 patients in 10\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe authors caution that these studies had different numbers of patients, different clinical features, different selection criteria, and different designs. The data must therefore be interpreted carefully.\u003c\/p\u003e\n\n\u003cp\u003eRegarding drug treatment before or after surgery, 6 articles described systemic therapies. These included hormonal treatment with or without chemotherapy (doxorubicin, taxol, capecitabine, gemcitabine) and\/or trastuzumab or lapatinib. Importantly, none of the patients in this review had received the newer targeted therapies such as pertuzumab, CDK4\/6 inhibitors, or immune checkpoint inhibitors.\u003c\/p\u003e\n\n\u003ch2 id=\"prognostic-factors\"\u003eWhich Factors Predict a Better Outcome?\u003c\/h2\u003e\n\n\u003cp\u003eSeveral factors consistently predicted who did better after surgery to remove liver metastases.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eHormone receptor–positive primary breast cancer\u003c\/strong\u003e was the most frequently identified favorable factor. Seven studies linked it to better overall survival. Three used multivariate analysis, a statistical method that adjusts for other factors at the same time. Four used univariate analysis, looking at one factor at a time.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eComplete removal of tumor (R0 resection)\u003c\/strong\u003e was associated with better overall survival in two multivariate and two univariate analyses.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eExtrahepatic metastases (cancer outside the liver)\u003c\/strong\u003e were linked to poorer overall survival in three multivariate analyses — patients whose cancer was confined to the liver did better.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSmaller liver tumors\u003c\/strong\u003e predicted better results. Liver metastases smaller than 3 cm were associated with better overall survival, while tumors 3.5 cm or larger were linked to poorer progression-free survival, according to three multivariate analyses. A univariate analysis also showed tumor size mattered.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFewer tumors\u003c\/strong\u003e also mattered. One multivariate and one univariate analysis found that patients with solitary (single) liver metastases had better overall survival, and the number of metastases was linked to both DFS and OS.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eLonger time before the cancer returned\u003c\/strong\u003e was favorable. Patients whose disease-free interval was 4 years or less had poorer OS and PFS in multivariate analysis, and those with DFS under 2 years had poorer OS in univariate analysis.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eResponse to drug therapy before surgery\u003c\/strong\u003e mattered too. Tumors were evaluated with RECIST criteria, the standard rules for measuring how tumors respond to treatment. No response to pre-operative systemic therapy was associated with progressive disease and poorer overall survival. One study reported that patients who had a partial response to chemotherapy had a median survival of nearly 80 months. This compared with approximately 30 months for patients whose response was less than partial — nearly a threefold difference.\u003c\/p\u003e\n\n\u003cp\u003eOther primary tumor characteristics — T stage, lymph node metastases, and tumor grade (how abnormal the cells look) — also influenced overall survival. Age appeared in the picture as well. One analysis found better outcomes in patients under 50, and another found better outcomes in patients over 50. This suggests that age alone is not a reliable guide.\u003c\/p\u003e\n\n\u003ch2 id=\"oligometastases\"\u003eOligometastatic Disease and Repeat Surgery\u003c\/h2\u003e\n\n\u003cp\u003eThe 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4) define oligometastatic disease. The definition is \"low volume metastatic disease with limited number and size of metastatic lesions (up to 5 and not necessarily in the same organ).\" Such disease is potentially amenable for local treatment. Local treatment is aimed at achieving a complete remission status.\u003c\/p\u003e\n\n\u003cp\u003eIn colorectal cancer, removing liver metastases is a well-established treatment. For breast cancer liver metastases, that approach remains controversial, even when only a few metastases are present.\u003c\/p\u003e\n\n\u003cp\u003eMore than 50% of the patients in the reports reviewed here had solitary liver metastases. One study noted significantly more long-term survivors among patients with solitary tumors, with survival reaching 60 months or more in some cases.\u003c\/p\u003e\n\n\u003cp\u003eOne research group reported a series of patients who underwent \"repeat hepatectomy\" (a second liver operation). They compared a single-hepatectomy group (120 patients) with a repeat-hepatectomy group (19 patients).\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSolitary liver metastases:\u003c\/strong\u003e 39% in the single-surgery group vs. 53% in the repeat-surgery group.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSurvival after the first operation:\u003c\/strong\u003e patients who went on to have repeat surgery lived longer than those who had only one operation — 95% and 84% vs. 50% and 38% at 3 and 5 years (P=0.002).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMedian survival:\u003c\/strong\u003e 35 months vs. 100 months.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNumber of tumors:\u003c\/strong\u003e patients with a single liver metastasis at first surgery had 3- and 5-year overall survival rates of 76% and 76%, compared with 51% and 17% in patients with multiple metastases (P=0.023).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eFactors predicting a better outcome after repeat hepatectomy included a time interval of more than 2 years between breast cancer diagnosis and the first liver operation. Other factors were a limited (smaller) resection, solitary metastases, positive progesterone receptor status, and chemotherapy given after the repeat operation. The authors concluded that repeat hepatectomy is potentially curative when combined with systemic therapy.\u003c\/p\u003e\n\n\u003cp\u003eAnother study looked specifically at resection of isolated liver metastases. Among 29 female patients, 16 (55%) had one liver metastasis and 6 (21%) had two. Median time from breast cancer to diagnosis of liver metastases was 55 months (range 1 to 77 months). The 1-year survival rate was 86% in patients who had surgery and 37.5% in those who did not. Complete removal (R0), fewer liver metastases, and a longer interval before the liver metastases appeared were significant prognostic factors.\u003c\/p\u003e\n\n\u003cp\u003eRecent studies show that subgroups of these patients with oligometastatic disease benefit from additional local or locoregional treatment. These patients have improved survival after complete (R0) removal of liver metastases compared with systemic treatment alone.\u003c\/p\u003e\n\n\u003ch2 id=\"case-control\"\u003eSurgery Plus Drug Therapy vs. Drug Therapy Alone\u003c\/h2\u003e\n\n\u003cp\u003eTo date, no prospective randomized trial (the strongest type of study, in which patients are assigned by chance to different treatments) has examined removal of breast cancer liver metastases. Instead, researchers have used case-control studies, in which surgically treated patients are compared with similar patients who received only drug therapy.\u003c\/p\u003e\n\n\u003cp\u003eIn one such study, 51 patients with BCLM were individually matched with patients receiving systemic treatment only. None had more than 4 liver metastases, and most had fewer than 4. Patients were matched for age, year of breast cancer diagnosis, time to metastases, TNM stage, hormone receptor status, and tumor pathology. The 3-year survival rates were \u003cstrong\u003e80.7% in the surgically treated group and 50.9% in the non-surgically treated group\u003c\/strong\u003e (P\u0026lt;0.0001).\u003c\/p\u003e\n\n\u003cp\u003eA second matched comparison used data from European patients. Matching was based on age, decade of diagnosis, time to metastases, maximum size of metastases, single vs. multiple tumors, chemotherapy, and hormonal or targeted therapy after diagnosis. Propensity score matching (a statistical technique that creates groups with similar characteristics and a similar likelihood of having surgery) was used.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMedian overall survival:\u003c\/strong\u003e 82 months with surgery plus systemic therapy vs. 31 months with systemic therapy alone (P\u0026lt;0.001).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e3-year overall survival:\u003c\/strong\u003e 81% vs. 69%.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e5-year overall survival:\u003c\/strong\u003e 33% vs. 24%.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRisk of death:\u003c\/strong\u003e patients treated with surgery plus systemic therapy were less likely to die than those given systemic therapy alone (hazard ratio 0.28; 95% confidence interval 0.15 to 0.52; P\u0026lt;0.001). This means the risk of death was about 72% lower in the surgery group.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eIn plain terms, patients who received systemic therapy combined with liver surgery lived more than twice as long as those given systemic therapy alone.\u003c\/p\u003e\n\n\u003cp\u003eA third case-control study compared 69 patients who had surgery and\/or ablation with 98 patients who received medical treatment only, with a median follow-up of 73 months. Patients in the surgical group tended to have estrogen receptor–positive tumors and to have received adjuvant chemotherapy and radiotherapy for their original breast tumor. Their liver tumor volume was smaller, and the time to diagnosis of liver metastases was significantly longer (53 months vs. 30 months) in the surgical group.\u003c\/p\u003e\n\n\u003cp\u003eIn this study, there was \u003cstrong\u003eno significant difference in overall survival\u003c\/strong\u003e between the surgical and systemic therapy groups (median 50 vs. 45 months; 5-year survival 38% vs. 39%). However, the surgical treatment group had a median recurrence-free interval of 28.5 months, and 10 patients (15%) remained free of recurrence after 5 years. The authors concluded that surgical treatment of BCLM might be applicable in carefully selected patients, with the goal of minimizing or avoiding systemic chemotherapy.\u003c\/p\u003e\n\n\u003ch2 id=\"risks\"\u003eRisks, Complications, and Hospital Stay After Surgery\u003c\/h2\u003e\n\n\u003cp\u003ePostoperative mortality (death within the period right after surgery) was 0% in five reports, 2% in one report, and 5% in one report. The median postoperative morbidity (rate of complications) was 28%, with a range of 18% to 42%.\u003c\/p\u003e\n\n\u003cp\u003eMajor complications developed in 3.5% to 12% of cases and included:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eMultiple organ failure\u003c\/li\u003e\n  \u003cli\u003eBiliary leakage (bile leaking from the liver's bile ducts)\u003c\/li\u003e\n  \u003cli\u003eBiliary fistula (an abnormal connection involving the bile ducts)\u003c\/li\u003e\n  \u003cli\u003eInfected intra-abdominal fluid collections, with or without the need for drainage\u003c\/li\u003e\n  \u003cli\u003eNeed for percutaneous drainage (draining fluid through the skin)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe median hospital stay after liver surgery was 8.5 days, with a range of 6 to 11 days.\u003c\/p\u003e\n\n\u003ch2 id=\"rfa\"\u003eRadiofrequency Ablation and Other Local Treatments\u003c\/h2\u003e\n\n\u003cp\u003eSeveral local treatments are available for breast cancer liver metastases. These include radiofrequency ablation (RFA, which uses heat to destroy tumors) and cryoablation (CRA, which uses extreme cold). They also include stereotactic radiofrequency ablation (SRFA), brachytherapy (internal radiation), and transarterial chemoembolization (TACE, which delivers chemotherapy directly into the liver's blood supply).\u003c\/p\u003e\n\n\u003cp\u003eRFA is particularly safe and effective and has been widely reported for BCLM. The RFA portion of this review covered 7 reports published from 2007 to 2018, with studies conducted between 1996 and 2015.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNumber of patients:\u003c\/strong\u003e median 43 per study (range 12 to 69); the abstract reports 266 patients in total, while the body of the review states 225.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNumber of treated tumors:\u003c\/strong\u003e median 87 per study (range 13 to 135), averaging 1.9 tumors per patient (range 1.1 to 2.1).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGuidance method:\u003c\/strong\u003e two series used computed tomography–guided RFA; five used ultrasound-guided RFA.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMean size of metastases:\u003c\/strong\u003e 2.4 cm (range 2 to 3.5 cm).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eExtrahepatic metastases:\u003c\/strong\u003e a mean of 36% of patients (reported as up to 40% to 83% across series).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eComplete response rate:\u003c\/strong\u003e median 86% (range 67% to 97%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSolitary liver metastasis:\u003c\/strong\u003e median 55.5% of patients (range 26% to 62%).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eSurvival after RFA\u003c\/h3\u003e\n\n\u003cp\u003eMedian follow-up in these reports was 24 months. Median disease-free survival was \u003cstrong\u003e11 months\u003c\/strong\u003e, median overall survival was \u003cstrong\u003e32 months\u003c\/strong\u003e, and the 3- and 5-year overall survival rates were \u003cstrong\u003e43% and 27%\u003c\/strong\u003e — about 3 in 10 patients alive at 5 years.\u003c\/p\u003e\n\n\u003cp\u003eComplication rates with RFA were lower than with surgical resection. Four studies reported major complication rates of 0%. The others reported rates of 1.1%, 2.3%, and 6.9%. The complications included severe intrahepatic bleeding (bleeding inside the liver) and injury to the bile duct. They also included thrombosis (clotting) of the portal branch, sepsis (a severe whole-body infection response), and cholecystitis (inflammation of the gallbladder). The median hospitalization period was \u003cstrong\u003e2 days\u003c\/strong\u003e (range 1 to 5 days).\u003c\/p\u003e\n\n\u003ch3\u003eRepeat RFA and tumor size\u003c\/h3\u003e\n\n\u003cp\u003eOne report described a patient who underwent three RFA sessions, achieving local control for 47 months. Another study found local tumor progression in 15 of 111 metastases at 3 months of follow-up, and five patients in that study received repeat RFA.\u003c\/p\u003e\n\n\u003cp\u003eTumor size matters with RFA. One group reported that a liver metastasis larger than 2.5 cm was linked to poor outcomes. Another reported on 69 patients with 135 liver metastases: local tumor progression occurred in 8 patients, 4 to 8 months after RFA. The rates of local progression according to the margin of healthy tissue around the treated tumor were:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e0 to 5 mm margin:\u003c\/strong\u003e 38.9% progressed\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMore than 5 to 10 mm margin:\u003c\/strong\u003e 3.6% progressed\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMore than 10 mm margin:\u003c\/strong\u003e 0% progressed\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAmong the 8 patients whose tumors progressed, 7 required repeat RFA.\u003c\/p\u003e\n\n\u003ch3\u003eHow RFA and surgery compare\u003c\/h3\u003e\n\n\u003cp\u003eThe clinical features that make a patient a good candidate for RFA differ from those favoring surgery. RFA is typically used for smaller tumors and in patients with a higher rate of cancer outside the liver: an average tumor size of 2.4 cm vs. 4.0 cm for surgery, and 46% vs. 27% with extrahepatic metastases. The merits of RFA are its high technical success rate, low rate of complications, short hospital stay, and the fact that it can be repeated.\u003c\/p\u003e\n\n\u003ch2 id=\"cost\"\u003eCost-Effectiveness of Liver Surgery\u003c\/h2\u003e\n\n\u003cp\u003eCost is an important consideration in cancer care. One research group evaluated the cost-effectiveness of liver resection using a Markov model. A Markov model is a mathematical model that simulates how patients move between health states over time. The group combined this with Monte-Carlo simulation, a method that tests many possible scenarios at once. They compared three groups:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003eLiver resection followed by conventional systemic therapy after surgery\u003c\/li\u003e\n  \u003cli\u003eConventional systemic therapy alone\u003c\/li\u003e\n  \u003cli\u003eNewer targeted therapy alone\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eThe authors concluded that liver resection is potentially more cost-effective than systemic therapy alone. This is especially true in patients who are positive for the estrogen receptor and\/or who are receiving newer systemic therapies.\u003c\/p\u003e\n\n\u003ch2 id=\"future\"\u003eFuture Directions: Combining Treatments\u003c\/h2\u003e\n\n\u003cp\u003eFor RFA, combining the procedure with other therapies such as immune checkpoint inhibitors may strengthen the body's antitumor immune response. Both radiotherapy and RFA combined with immune checkpoint inhibitors can trigger a distant antitumor response — an effect in which treating one tumor causes tumors elsewhere in the body to shrink. This is called an abscopal immune-priming effect (a \"priming\" of the immune system that reaches beyond the treated site). Research in this area is still developing.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThis review suggests that removing or ablating breast cancer liver metastases can offer meaningful survival for carefully selected patients. The median overall survival after surgery was 39.5 months, and 38% of patients — about 4 in 10 — were alive at 5 years. With systemic therapy alone, 10-year survival is about 5%.\u003c\/p\u003e\n\n\u003cp\u003eThe most favorable profile is a patient whose original breast cancer was hormone receptor–positive. The patient's liver tumors are small and solitary, and the cancer has not spread outside the liver. The surgeon can remove all visible disease with clear margins. Patients with these features had the best outcomes across multiple analyses.\u003c\/p\u003e\n\n\u003cp\u003eRFA offers a less invasive alternative with a shorter hospital stay — a median of 2 days versus 8.5 days for surgery — and lower complication rates. However, survival after RFA was shorter: a median of 32 months and a 5-year survival of 27%. RFA's advantage is that it can be repeated if new tumors appear.\u003c\/p\u003e\n\n\u003cp\u003eLiver surgery also provides tissue for testing the metastatic tumor's receptor status (estrogen receptor, progesterone receptor, and HER2), which can guide later drug treatment choices. That is a benefit beyond survival alone.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What This Review Cannot Prove\u003c\/h2\u003e\n\n\u003cp\u003eSeveral important caveats apply to these findings. First, there have been no prospective randomized trials of liver surgery for breast cancer liver metastases. Without randomization, doctors cannot be certain that surgery itself caused the longer survival. Patients chosen for surgery tend to be healthier and to have less extensive cancer to begin with.\u003c\/p\u003e\n\n\u003cp\u003eSecond, the studies in this review varied widely. They enrolled different numbers of patients (12 to 131), used different selection criteria, and had different designs and follow-up periods. The authors state plainly that the data must be carefully interpreted for these reasons.\u003c\/p\u003e\n\n\u003cp\u003eThird, surgical patients in the case-control studies were matched but not randomized, and matching can never account for every difference between groups.\u003c\/p\u003e\n\n\u003cp\u003eFourth, none of the patients in this review received the newest drug therapies, such as pertuzumab, CDK4\/6 inhibitors, or immune checkpoint inhibitors. Since those drugs improve outcomes on their own, the relative benefit of surgery may differ in patients treated today.\u003c\/p\u003e\n\n\u003cp\u003eFifth, the RFA data are limited. Complication reporting was inconsistent, follow-up was short (a median of 24 months), and some series were small.\u003c\/p\u003e\n\n\u003cp\u003eFinally, the patient counts for the RFA review itself were inconsistent — the abstract reports 266 patients and the body text reports 225, which reflects the uneven quality of the underlying literature.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003ePractical Recommendations\u003c\/h2\u003e\n\n\u003cp\u003eBased on this review, patients with breast cancer that has spread to the liver may want to consider the following:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk whether you meet the favorable criteria.\u003c\/strong\u003e The best candidates have hormone receptor–positive primary tumors. They also have small (under 3 cm) or single liver metastases, no cancer outside the liver, and tumors that can be completely removed with clear margins.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about the goal of treatment.\u003c\/strong\u003e In selected patients, surgery or ablation may reduce or delay the need for continuous systemic chemotherapy.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss tissue testing.\u003c\/strong\u003e Liver surgery provides tumor tissue that can confirm the receptor status (estrogen receptor, progesterone receptor, HER2) of the metastatic disease, which may change your drug treatment plan.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eWeigh the risks.\u003c\/strong\u003e Postoperative death occurred in 0% to 5% of patients across reports, and complications occurred in about 28% (range 18% to 42%). Major complications occurred in 3.5% to 12%. The typical hospital stay was 8.5 days.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConsider RFA if surgery is not suitable.\u003c\/strong\u003e RFA has a high technical success rate, lower complication rates, a median hospital stay of about 2 days, and can be repeated. It is generally used for smaller tumors.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about repeat procedures.\u003c\/strong\u003e In one series, patients who had a second liver operation had dramatically better survival than those who had only one (median 100 vs. 35 months; 95% and 84% vs. 50% and 38% alive at 3 and 5 years).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSeek care at an experienced center.\u003c\/strong\u003e Nine of the 11 surgical studies were single-center analyses, and outcomes depend heavily on surgical expertise and patient selection.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWho might be a good candidate for surgery to remove breast cancer that has spread to the liver?\u003c\/h3\u003e\n\u003cp\u003eAcross the reviewed studies, the most favorable features were a hormone receptor–positive original breast cancer. Other favorable features were liver tumors that are small (under 3 cm) or single. Other favorable features were no cancer outside the liver and tumors that can be completely removed with clear margins. Patients with these features had better outcomes in multiple analyses, but no randomized trial has compared surgery with drug therapy alone.\u003c\/p\u003e\n\u003ch3\u003eWhat survival can I expect after liver surgery for breast cancer liver metastases?\u003c\/h3\u003e\n\u003cp\u003eIn the pooled surgical series, median overall survival was 39.5 months, and 38% of patients — about 4 in 10 — were alive at 5 years. These numbers come from studies with different patient groups and selection criteria, and none of the patients received the newest drug therapies, so they must be interpreted carefully.\u003c\/p\u003e\n\u003ch3\u003eHow does radiofrequency ablation (RFA) compare with surgery for these liver tumors?\u003c\/h3\u003e\n\u003cp\u003eRFA uses heat to destroy tumors without surgery. In the reviewed reports, median survival after RFA was 32 months and 5-year survival was 27%, compared with 39.5 months and 38% after surgery. RFA is less invasive, requires about 2 days in hospital, has lower complication rates, and can be repeated, but it is generally used for smaller tumors.\u003c\/p\u003e\n\u003ch3\u003eWhat are the risks and recovery time after liver surgery for breast cancer metastases?\u003c\/h3\u003e\n\u003cp\u003eAcross the reports, postoperative death occurred in 0% to 5% of patients. Complications occurred in about 28% (range 18% to 42%), with major complications in 3.5% to 12%. The median hospital stay was 8.5 days (range 6 to 11 days). These figures come from selected patients in studies without randomization.\u003c\/p\u003e\n\u003ch3\u003eCan liver surgery help if my cancer has spread outside the liver?\u003c\/h3\u003e\n\u003cp\u003eIn the reviewed studies, cancer outside the liver was linked to poorer overall survival in three multivariate analyses. Patients whose cancer was confined to the liver did better. However, some patients with extrahepatic metastases still had surgery, and the studies varied in how they selected patients, so individual situations differ.\u003c\/p\u003e\n\u003ch3\u003eWhat does a median survival of 39.5 months mean?\u003c\/h3\u003e\n\u003cp\u003eMedian survival means that half of the patients in the pooled surgical series lived longer than 39.5 months and half lived less. It does not predict any one person's outcome. The range across studies was 26 to 82 months, and these results come from selected patients, not from a randomized trial.\u003c\/p\u003e\n\u003ch3\u003eIs a second liver operation ever considered?\u003c\/h3\u003e\n\u003cp\u003eIn one series, patients who had a repeat hepatectomy (a second liver operation) lived longer than those who had only one. Median survival was 100 months versus 35 months. At 3 and 5 years, 95% and 84% versus 50% and 38% were alive. This was a small comparison, and repeat surgery is not suitable for everyone.\u003c\/p\u003e\n\u003ch3\u003eWhen should a patient with breast cancer that has spread to the liver seek a second opinion about liver surgery or ablation?\u003c\/h3\u003e\n\u003cp\u003eA second opinion is worth seeking when the liver is the only site of spread. A second opinion is also worth seeking when the tumors are small (under 3 cm) or solitary. A second opinion is also worth seeking when the original cancer was hormone receptor–positive. These features are linked to the longest survival after surgery. It also helps when it is unclear whether surgery, radiofrequency ablation, or drug therapy alone is appropriate, since no randomized trial has compared them. A review of records and imaging can clarify whether all visible tumor can be completely removed. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Surgical therapy for breast cancer liver metastases\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication details:\u003c\/strong\u003e Translational Cancer Research, 2020; volume 9, number 8, pages 5053–5062. doi: 10.21037\/tcr-20-1598. Submitted March 20, 2020; accepted May 15, 2020.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eNote:\u003c\/strong\u003e This patient-friendly article is based on peer-reviewed research. It summarizes a review of published studies and does not replace personalized medical advice from your oncology team.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47458215755932,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0599\/5449\/5644\/files\/ddn-medical-article-treating-breast-cancer-that-has-spread-to-the-liver-a-complete-guide-to-surgery-and-radiofrequency-ablation-hero.png?v=1790202352","url":"https:\/\/diagnosticdetectives.com\/da\/products\/treating-breast-cancer-that-has-spread-to-the-liver-a-complete-guide-to-surgery-and-radiofrequency-ablation","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}