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ORIGINAL ARTICLES |
From the Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Correspondence: Address correspondence and reprint requests to: Jean-Nicolas Vauthey, MD, Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030; Fax: 713-792-0722; E-mail: jvauthey{at}mdanderson.org
| ABSTRACT |
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Methods: Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases.
Results: Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates.
Conclusions: In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.
Key Words: Breast cancer Surgery Metastasis Radiofrequency ablation
| INTRODUCTION |
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Recent studies suggest a role for surgical resection in a subset of patients with isolated metastases in the liver, brain, lung, and bone.7 Single institutional series have demonstrated 5-year survival rate of 20% to 27% following hepatic resection of BCLM.8,9 Liver resection is a safe procedure in most centers, with an operative mortality of <5% and a morbidity of 20%.10 Hepatic resections are most commonly done for colorectal liver metastasis, with 5-year survival rates of 25% to 44% being reported.11 The contemporary role of hepatic resection for metastasis from other malignancies (e.g., breast cancer) is not clearly defined.
Since the early 1990's, liver resection has been used at the University of Texas M. D. Anderson Cancer Center to treat selected patients with isolated hepatic metastases from breast cancer. This study was conducted to analyze the experience with liver resection or ablation in our institution and to assess its role in the treatment of BCLM.
| METHODS |
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Clinical and pathologic parameters reviewed included the following: age at diagnosis, race, tumor size, lymph node status, stage, estrogen and progesterone receptor status, tumor margin status, chemotherapy or hormonal therapy, and locoregional and distant recurrence. Also recorded were characteristics of liver metastases, including size, number, and location of metastases; the type and the length of surgical procedures; intraoperative blood loss; and postoperative complications.
The diagnosis of metastasis was confirmed by percutaneous liver biopsy. Patients then had a staging evaluation that included history and physical examination, serum chemistries (complete blood count, transaminases [aspartate aminotransferase, alanine aminotransferase], alkaline phosphatase, bilirubin), chest radiograph, computed tomography (CT) of the abdomen and pelvis, and bone scan.
Patients were treated with preoperative, postoperative, or both chemotherapy and hormonal therapy regimens, according to institutional protocols in use at the time of diagnosis of metastases. Response was assessed by imaging studies, including liver ultrasound and abdominal CT.
Patients with extrahepatic disease were considered ineligible for resection. A standardized approach was used for intraoperative staging, which included a thorough exploration of the peritoneal cavity and biopsy of any suspicious lesions. Periportal nodes were also examined, with any suspicious nodes or those >1 cm in size sent for frozen section evaluation. If no extrahepatic disease was detected, patients were evaluated by intraoperative ultrasound (IOUS). An IOUS with a 5- to 7.5-MHz probe (Aloka, Co. Ltd., Tokyo, Japan) was used to assess the extent of the known metastases and to search for additional lesions. The liver was fully mobilized by dividing the triangular ligaments, round ligament, and falciform ligament.
Surgical procedures for hepatic lesions were determined on the basis of disease extent and location. If IOUS demonstrated that each lesion could be treated, patients had resection aimed at a surgical clearance margin of at least 1 cm or combined resection plus radiofrequency ablation (RFA) with a 1-cm margin. Hepatic resection consisted of major hepatectomy (three or more segments resected) or minor hepatectomy (fewer than three segments resected). Surgical margins were evaluated intraoperatively. RFA was performed through an open technique if the tumor to be ablated was unresectable because of location or distribution. Ablation was performed using the RF 2000 or 3000 generator system (Boston Scientific Corp., Natick, MA) and a 15-gauge insulated LeVeen monopolar needle electrode (4.0 cm maximal array was used), placed under IOUS guidance, and ablation performed using a previously described technique.12
The Statistical Package for the Social Sciences, version 10.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. Statistical analysis was performed only on patients having hepatic resection of BCLM. Differences in the distribution of characteristics were analyzed by the
2 test. Disease-specific and disease-free interval probabilities were calculated by the Kaplan-Meier product limit method from the dates of liver surgery to the date of death or last follow-up. Possible prognostic factors in term of survival after liver surgery were assessed, including age at diagnosis of breast cancer, characteristics of the primary breast cancer, type of treatment, disease-free interval, number of liver metastases, the size of liver metastases, response to systemic treatment, type of surgery performed using log-rank test. P values
.05 were considered to be statistically significant.
| RESULTS |
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| DISCUSSION |
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Because the mortality and morbidity associated with liver resection has decreased dramatically during the past decade, the indication for surgery has widened for metastatic diseases. Hepatic resection, therefore, can be offered to selected patients with isolated disease to render them disease free, or at least disease stable. A recent report of the Institute Curie in Paris19 found two factors to be predictive of outcome: the time to metastasis to the liver and the initial stage of breast cancer. Because of the small number of patients in this series, we were unable to identify specific prognostic factors that affected survival after resection. Selection criteria are still controversial; however, important criteria are likely to be fewer than four metastases, no extrahepatic disease, and demonstrated disease regression or stability with systemic therapy before resection. We had one patient who experienced recurrence very early after hepatic resection and died within 6 months. At the time of surgery, it was noted that this patient had extensive (seven separate lesions) left lobe disease. Additionally, she had 6 months of preoperative chemotherapy, during which time her hepatic disease progressed. This suggests, perhaps, that systemic disease progression in this patient on chemotherapy also likely occurred. The extent and behavior of disease can indicate a more aggressive biology and, perhaps, those patients who have not demonstrated disease stability or regression during preoperative chemotherapy should not be considered for resection.
As the treatment recommendations for breast cancer continue to evolve, so too does the goal of surgical intervention. We may be approaching the time when the goal for the treatment for metastatic breast cancer is to render it harmless as a result of prolonged remission. In our series, 52% of the patients eventually developed recurrent metastatic disease, usually not in the liver, with a mean recurrence time of 21 months after treatment. Of those patients with recurrent disease, 50% remain alive and are doing well clinically. Most of these patients remain on some type of long-term chemotherapy. The optimal treatment for selected patients with isolated metastases can include, as in our patients, a combination of chemotherapy or hormonal therapy and hepatectomy.
In light of the fact that surgical treatment can be performed with low morbidity and minimal mortality (61% 5-year survival rate), hepatic resection can be proposed in this selected group of patients. Further studies need to be conducted to define which patients best benefit from this treatment strategy. We recommend an extensive preoperative staging evaluation before considering hepatic resection for BCLM. Radiographic studies include CT of the chest, abdomen, and pelvis; bone scan and, perhaps, positron emission tomography (PET) scan. Recent studies suggest that PET imaging can identify metastases that are not seen with other types of imaging.19,20 Our preference is that chemotherapy be given before hepatic resection. After two to three cycles of chemotherapy, radiographic studies are then repeated. Hepatic resection can be considered for patients with stable or improved disease isolated to the liver who have tumors that are resectable with a tumor-free margin or amenable to RFA. Laparoscopy is recommended to prevent nontherapeutic laparotomy if extrahepatic disease based on preoperative imaging is suggested. In our study, two patients with BCLM had unsuspected extrahepatic disease found at laparotomy. Hepatic resection is preferable if metastases can be safely removed with a negative surgical margin. Because of the higher local recurrence rates seen with RFA for colorectal metastases as compared with resection,21 RFA should be reserved for those patients with tumors not amenable to safe resection.
The biology of this subset of patients with isolated liver metastases, or single organ stable metastases, requires further study. This is particularly so in light of improving chemotherapeutic strategies because the natural history of these patients can differ from patients with multiorgan, metastatic breast cancer, or large tumor burdens. By changing our focus from complete eradication of all viable tumor cells as the goal of therapy to that of rendering the disease stable, selected patients with metastatic breast cancer to the liver may have prolonged remission if their cancer is detected early and treated aggressively. Further studies are needed to answer this question.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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Received for publication January 9, 2004. Accepted for publication May 14, 2004.
| REFERENCES |
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