Liver resection for breast cancer-related liver metastases: a case report

Abstract

Introduction

Breast cancer liver metastasis presents a significant challenge in clinical oncology, with limited treatment options and poor prognosis. This case series study explores the extended survival achieved in breast cancer patients with liver metastases through a combination of surgical and medical interventions.

Case presentation

We present three cases of Javanese female patients with breast cancer (51 years old, 42 years old, and 55 years old) with liver metastases who underwent hepatic resection followed by systemic therapy. The cases illustrate successful outcomes with disease-free survival ranging from 5 to 31 months post-surgery. Key prognostic factors associated with improved survival include prolonged interval between initial diagnosis and detection of liver metastasis, liver-limited disease, positive response to preoperative systemic therapy, and expression of estrogen and progesterone receptors in the metastatic lesions.

Conclusion

These findings underscore the potential efficacy of a multidisciplinary approach integrating local hepatectomy with systemic therapy in selected patients with breast cancer liver metastasis. Further research is warranted to identify optimal patient selection criteria and refine treatment strategies for improved outcomes.

Introduction

Breast cancer stands as the most prevalent cancer in females globally, surpassing lung cancer in 2020 with 2.26 million new cases reported, compared with 2.2 million for lung cancer [1]. Liver metastasis affects approximately 50% of those with metastatic breast cancer, and 5–12% experience a recurrence in the liver [2]. The prognosis post-liver metastasis is grim, with a median survival rate of 2–3 years if treated with systemic chemotherapy and liver resection surgery, and an overall survival time of 4–8 months without intervention, making it a major cause of death in advanced breast cancer patients [3, 4].

Several studies have presented conflicting findings regarding the survival rates following locoregional hepatic treatment in patients with metastatic breast cancer (MBC) with liver metastases, with reported 3-year and 5-year survival rates ranging from 49% to 94% and 5% to 78%, respectively [4, 5]. A recent review by Bale and colleagues highlighted that certain primary tumor characteristics, such as small size, absence of lymph node involvement, low grade, and early stage, may correlate with improved outcomes following liver surgery [4]. They also identified several independent positive prognostic factors, including a prolonged interval between the initial diagnosis and the detection of breast cancer liver metastasis (BCLM) exceeding 1 year, liver-limited disease (excluding isolated pulmonary and bone metastases), positive response to preoperative systemic therapy before hepatic surgery, and expression of estrogen receptor (ER) and progesterone receptor (PgR) by the BCLM [4].

At the time of death, 40–60% of patients with breast cancer experience liver metastasis. While most liver metastases do not show symptoms, there are occasional instances where patients develop disseminated intrasinusoidal metastatic liver disease (DISML), which can result in acute liver failure and, ultimately, death [5]. Additionally, less than 10% of patients with breast cancer present with liver metastasis, and its presence at diagnosis is associated with an unfavorable prognosis, yielding a median survival of only 12 months [6]. Liver metastasectomy could provide a survival benefit over systemic chemotherapy alone for selected patients with BCLM.

Yet, the independent prognostic factors for predicting survival outcomes remain undefined. The combination of local hepatectomy and effective systemic therapy, aimed at cure, demonstrates potential efficacy in treating patients with breast cancer liver metastasis. We present a case series on patients with breast cancer experiencing early isolated liver recurrence who have survived without any further recurrence. While the combination of local hepatectomy and systemic therapy shows promise for improving survival outcomes in patients with breast cancer with isolated liver metastases, the adoption of this approach has been limited owing to historical treatment paradigms, resource constraints, and the need for robust, evidence-based guidelines.

Case illustrations

Case 1

A 51-year-old woman presented in May 2020, initially diagnosed with non-special type (NST) grade II invasive carcinoma of the left breast, T2N0M1, luminal A, human epidermal growth factor receptor 2 (HER2) negative, with concurrent lung and liver metastases. After undergoing a modified radical mastectomy (MRM) for the left breast, she completed six cycles of adjuvant chemotherapy with docetaxel, and continued with hormonal therapy. Physical examination revealed hepatomegaly extending 4 cm below the costal margin but no symptoms of weight loss, abdominal pain, or appetite loss. The examination was otherwise normal, with no signs of anemia, jaundice, or lymphadenopathy.

Magnetic resonance imaging (MRI) of the abdomen in August 2020 identified five rim-enhanced nodules in liver segments 6, 7, and 8, with the largest nodule measuring approximately 2.8 × 2.4 × 2.2 cm in segment 8, suggestive of metastasis (Fig. 1). No extrahepatic disease was observed after chemotherapy. The patient was subsequently referred to a hepatobiliary surgical unit for further management. After a satisfactory anesthetic assessment, she underwent a right segmentectomy to resect the solitary liver lesion. Histology confirmed the presence of metastatic adenocarcinoma from the invasive carcinoma luminal type (Fig. 2). The surgical resection was successful (R0), achieving disease-free clearance margins. A follow-up MRI showed no remaining nodes in the liver in May 2021. As of the latest update, the patient is currently continuing maintenance therapy with hormonal therapy letrozole and goserelin. She remains fit, well, and disease-free following the curative-intent resection.

Fig. 1

Magnetic resonance imaging of abdomen with contrast. Before hepatectomy, there were five rim-enhanced nodules in segments 6, 7, and 8 of the liver, suggesting metastasis. Following hepatectomy, no nodules are observed in the liver, spleen, or pancreas

Fig. 2

Anatomy pathology. The liver tissue sections show swollen, hyperemic hepatocyte lobules, among which malignant cells with round oval nuclei, pleomorphic, hyperchromatic, coarse chromatin, prominent nucleoli, eosinophilic cytoplasm, and mitosis can be found, arranged to form glandular structures (A). Immunohistochemical examination of excised liver lobe (× 10 magnification). Positive expression of hepatocyte GATA-3 (B) and mammoglobin (C) in tumor cells

Case 2

A 42-year-old woman presented with lumps in her left breast that had been developing over the past year, measuring 2 cm in size. Ultrasound imaging revealed a breast imaging reporting and data system (BIRADS) category 4 mass in the left breast and a BIRADS category 3 mass in the right breast. Following a core biopsy of the left breast lump, histopathology confirmed invasive carcinoma of the left breast, identified as luminal B and HER2 negative (Fig. 3). The patient underwent neoadjuvant chemotherapy using doxorubicin–cyclophosphamide (AC) for three cycles, followed by a modified radical mastectomy (MRM). The surgical resection was successful (R0), achieving disease-free clearance margins. Postoperative management included chemotherapy paclitaxel every 3 weeks and tamoxifen plus Zoladex (goserelin) for ovarian suppression. Further ultrasound evaluations reported a benign BIRADS 3 mass in the right breast and reactive lymphadenopathy, leading to locoregional radiation therapy consisting of 30 sessions. After 1 year, an MRI of the abdomen revealed metastatic nodes in the liver’s seventh and eighth segments, measuring 3.7 × 2.7 × 1.6 cm, indicative of liver metastasis (Fig. 4). The patient was referred to the hepatobiliary surgery unit and underwent segmentectomy to remove the liver nodes in November 2023. Histopathology confirmed metastatic adenocarcinoma, likely of breast origin. A follow-up MRI showed no remaining nodes in the liver in September 2023. As of the latest update, the patient is currently undergoing maintenance therapy with letrozol and goserelin. She remains fit, well, and disease-free following the curative intent resection.

Fig. 3

Anatomy pathology. The preparation from the liver consists of liver cells containing 2–3 cells per plate, in the swollen hepatic parenchyma, hyperemic. Among these, there is infiltration of malignant epithelial cells arranged to form glandular structures approximately 95 percent, the rest are solid. These cells have round to oval nuclei, are pleomorphic, hyperchromatic, with chromatin coarse to vesicular, prominent nucleoli, eosinophilic and vacuolated cytoplasm. Lymphovascular invasion is observed. A 100× magnification; B 400× magnification

Fig. 4

Magnetic resonance imaging of abdomen with contrast. Before hepatectomy, a solitary iso-hypodense lesion with clear boundaries and regular edges is visible in segment 7 of the liver (size ± 4.6 × 3.7 cm) attached to the right hepatic vein, showing inhomogeneous enhancement after contrast administration. Following hepatectomy, no solid mass is visible in the liver

Case 3

A 55-year-old woman was diagnosed with T3N1M1, stage IIIB invasive carcinoma of the right breast in May 2019 (Fig. 5). Immunohistochemistry showed ER (+), PgR (+), Her2 (3+). Her family history was unremarkable for breast cancer. Initial treatment included mastectomy followed by adjuvant chemotherapy with trastuzumab (440/350), docetaxel (120 mg), and epirubicin (100 mg). The patient received regular cycles of trastuzumab and chemotherapy every 21 days. Additionally, hormonal therapy with tamoxifen (20 mg) and goserelin (3.6 mg) was initiated owing to ER and PR positivity. By 2021, liver metastasis was detected, and hepatic resection was performed. Post-operative treatment involved pertuzumab (840/420), trastuzumab (440), and paclitaxel (270). This regimen continued until September 2022, with notable improvements in tumor markers and imaging studies.

Fig. 5

Computed tomography scan showed multiple nodules in the liver parenchyma, with sizes of 10.4 mm in segment III and 13.2 × 21.3 mm in segment IVa, accompanied by ascites and multiple mesenteric lymph nodes, suggesting a metastatic process. Splenomegaly was also observed

However, the patient experienced a decline in October 2022, marked by increased bilirubin levels and deteriorating liver function tests. Ado-trastuzumab emtansine (160 mg) was initiated, leading to significant clinical improvements. Subsequent treatments were adjusted on the basis of regular imaging and laboratory tests. The patient continued to be monitored closely with regular imaging and blood tests. By March 2024, she exhibited signs of pleural effusion and ascites, indicating disease progression and leading to respiratory failure. The patient succumbed to the illness in March 2024.

Discussion

Although advancements have been made in the systemic treatment of MBC, patients with this condition typically have a median survival ranging from 18 to 24 months [7,8,9,10,11,12]. For certain individuals, undergoing surgery to remove liver metastases from breast cancer may offer a viable treatment option. Optimal outcomes are achieved when this surgical intervention is conducted in specialized centers with high expertise and after careful multidisciplinary evaluation, as is customary in managing other types of cancer [13]. A recent systematic review focusing on liver metastasis resection in MBC indicated a median overall survival (OS) of 35.1 months and a median disease-free survival (DFS) of 21.5 months. Furthermore, a comparative analysis showed that patients who underwent resection had a significantly higher median OS of 82 months compared with 31 months for those receiving only systemic therapy, suggesting that combining surgery with systemic treatment leads to better overall survival outcomes [14].

The study’s population in Orlandi et al. exhibited a median overall survival (OS) of 67 months and a disease-free interval (DFI) of 15 months, suggesting a potential survival advantage for patients undergoing liver surgery for metastases, particularly those achieving R0 resection [15]. Specifically, the presence of a negative resection margin emerged as the sole factor significantly impacting OS (78 versus 16 months; HR 0.083, p < 0.0001) and DFI (16 versus 5 months; HR 0.17, p = 0.0058). Among the 20 patients with R0 resection, 13 had a solitary lesion while 7 had two metastases, underscoring the importance of cautiously selecting patients with limited liver disease to optimize surgical outcomes. Several researches have indicated that patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive breast cancer liver metastases (BCLM) may benefit from liver metastasectomy, given their favorable tumor characteristics and the potential for hormone therapy administration [15]. Similarly, primary breast cancer features such as small tumor size, absence of lymph node involvement, low grade, and early stage have been associated with better outcomes following liver metastasectomy. Conversely, individuals with a triple-negative phenotype in both primary breast cancer and liver metastases may not derive significant benefits from liver metastasectomy owing to the aggressive nature of their tumors and limited treatment options [16].

Study by Millen et al. discovered that a positive hormonal status correlates with better survival rates in patients who had liver resection (LR). While Wyld et al. identified estrogen receptor (ER) positivity as a favorable prognostic factor, research analysis revealed that any receptor status with a positive component (except for ER− PR+ HER2−, owing to a limited sample size of 21 patients) independently associated with improved survival [17]. A recent study from MD Anderson Cancer Center found that patients receiving LR in addition to chemotherapy had a 56% 5-year overall survival (OS) rate, compared with 40% for those on chemotherapy alone. Their research showed that patients with basal-like (triple-negative breast cancer (TNBC)) and HER2-negative tumors had worse survival compared with those with luminal A, luminal B, and HER2 enriched subtypes. In their cohort of 47 HER2+ patients, 91% received targeted therapy [18]. They proposed that the survival benefits might be owing to the enhanced effectiveness of systemic and targeted therapies. Notably, HER2 enriched tumors were the most common among patients with metastatic disease confined to the liver. In the MD Anderson study, surgery provided the greatest survival advantage for patients with HER2 enriched tumors, with median OS rates of 81 months with LR versus 30 months without [18]. Their results similarly indicated that triple-negative status is linked to higher mortality compared with ER+ and/or HER2+ status. However, TNBC patients who received LR and chemotherapy showed better survival rates than those who had chemotherapy alone, suggesting that surgery might play a beneficial role even for this group.

Another factor influencing the prognosis of patients with breast cancer following metastasectomy is their response to preoperative systemic therapy [19]. Successful eradication of microscopic metastatic tumors in the liver and systemic organs through systemic therapy may enhance the effectiveness of aggressive local treatments for limited BCLM, potentially leading to improved survival outcomes [20]. Additionally, the response to systemic therapy can guide postoperative treatment decisions. Conversely, patients who do not exhibit disease regression or stability with systemic chemotherapy may not be suitable candidates for liver metastasectomy [21]. Furthermore, the presence of HER2 overexpression on hepatic metastases has been linked to enhanced survival rates [22]. According to a meta-analysis, the combined discordance rate between primary and recurrent breast cancer was documented at 8% among patients with HER2, 20% among those with ER, and 33% among those with PgR [23]. Additionally, it has been proposed that the mutation rate of the metastatic phenotype tends to be lower at earlier recurrence sites. Notably, no biological alterations were observed in the current patient between the primary tumor and the corresponding asynchronous liver metastasis [22, 23]. Chemotherapy guided by response assessment for liver metastasis might also prove effective against systemic micro-metastases, thereby contributing to prolonged survival without the need for continuous chemotherapy. Given the significant advancements in the efficacy of HER2-directed therapy, the potential utilization of local therapy for treating limited BCLM could further expand, particularly in patients with HER2 overexpression in hepatic metastases [23].

The typical approaches for addressing liver metastasis involve systemic chemotherapy and arterial injection chemotherapy through a catheter inserted into the hepatic artery. Although systemic chemotherapy shows a relatively positive response rate, its effectiveness is limited by a short duration of response, offering no significant impact on prognosis. According to O’Reilly et al.’s analysis of 312 patients, the median survival following the diagnosis of liver metastasis was reported to be 3.8 months [17]. As for arterial injection chemotherapy, Fraschini et al. documented a 36% response rate with a median survival of 11 months. Stehlin et al.’s findings indicated a 45% response rate, with a median survival of 16 months among responders. Moreover, they reported a notable case where the longest survival reached 5 years [18]. The combination of local hepatectomy and effective systemic therapy, aimed at cure, demonstrates potential efficacy in treating patients with breast cancer liver metastasis. Liver metastasectomy could provide a survival benefit over systemic chemotherapy alone for selected BCLM patients. Yet, the independent prognostic factors for predicting survival outcomes remain undefined. There is a pressing need for further research to identify patients who could significantly benefit from an aggressive, multidisciplinary treatment approach, including liver metastasectomy.

Conclusion

Breast cancer liver metastasis presents a formidable clinical challenge, with limited treatment options and poor prognosis. However, the cases presented in this series illustrate the potential efficacy of liver metastasectomy in selected patients, offering hope for disease-free survival. A multidisciplinary approach integrating local hepatectomy with systemic therapy holds promise in improving outcomes for individuals with BCLM. A key takeaway from this study is the importance of a multidisciplinary team (MDT) approach in managing these complex cases. The collaboration between surgical oncologists, medical oncologists, and other specialists is crucial for optimizing treatment strategies and improving patient outcomes. MDTs are well-positioned to tailor interventions on the basis of individual patient profiles and tumor characteristics, thereby enhancing the efficacy of both surgical and systemic treatments.