Commentary (Hwang/Esserman): Surgical Management of Hepatic Breast Cancer Metastases

In this review of hepatic resection for metastatic breast cancer, the authors argue that a small group of women with isolated liver metastases may be appropriate candidates for surgical resection. Although some data have been reported, the few published studies represent small, retrospective single-institutional series with no standardized criteria for resection. Nevertheless, the potential prospect of improved patient outcome in the setting of liver metastases from breast cancer deserves further consideration. Tumor Biology
The rationale for resection of metastatic lesions in breast cancer patients runs counter to our current understanding of the biology of metastatic disease. Since stage IV disease by definition is a manifestation of cancer progression outside the primary tumor site, it represents systemic progression that is not likely to be curable by regional treatment only. One possible exception to this is in the setting of colorectal metastasis to the liver. Due to the anatomic drainage pattern of the colon and rectum, liver metastasis may represent the sole site of extracolonic dissemination and may not be associated with occult disease elsewhere. In patients who undergo complete resection of hepatic metastases, the 5-year survival can exceed 30%.[1,2] However, even in this patient population, indicators of increased systemic involvement based on nodal status, high preoperative carcinoembryonic antigen levels, and multiple metastases predict a poor outcome following hepatic metastasectomy. Hepatic involvement is rarely the first site of metastasis in breast cancer, seen in no more than 5% of patients with newly diagnosed stage IV disease.[3] Visceral metastasis in breast cancer patients has been associated with short disease-free survival, high-grade disease, and poor prognosis. Thus, patients with liver involvement are likely to have a short time to disease progression, and a narrow window in which surgical resection may potentially have an impact. Furthermore, even liver metastases amenable to resection often indicate additional occult disease. In at least two studies, over half of patients undergoing liver metastasectomy for breast cancer developed subsequent metastatic disease in the liver.[4,5] Given the morbidity of hepatectomy, preoperative radiographic confirmation of resectability remains critical. Patient Selection
Despite the above concerns, it is noteworthy that several series have demonstrated favorable survival following hepatic resection for metastatic breast cancer. As with many invasive interventions in the metastatic setting, careful patient selection is a critical determinant of outcome. The authors suggest that there may exist a limited population of patients with metastatic disease who may benefit from such a procedure. This population would necessarily exclude those with extrahepatic disease or extensive disease in the liver, poor performance status, or a short disease-free interval. Although some studies have shown a worse prognosis after liver resection in patients with estrogen receptor (ER)-negative disease, it is not yet clear whether this factor alone should exclude a patient from consideration of hepatic resection if other criteria are met. It important to consider, however, that the improved outcome seen in patients undergoing liver resection may stem from tumor biology rather than the intervention itself. A solitary liver metastasis and long disease-free interval may represent indolent disease rather than serve as an indicator of who may benefit from hepatic resection per se. Importantly, the largest reported series of such patients showed no association between the extent of surgical resection (R0, R1, or R2) and outcome,[5] calling into question whether the relationship between hepatic resection and prognosis is, in fact, a causal one. Neaodjuvant Chemotherapy for Liver Metastasis
Although no standardized chemotherapy protocol exists for preoperative treatment of stage IV breast cancer, neoadjuvant treatment is gaining increased acceptance in the treatment of colorectal hepatic metastases. The rationale for this approach includes the fact that it improves resectability and allows for a more durable response by combining local and systemic therapy. This approach may be particularly attractive when treating hepatic metastasis in breast cancer, since a neoadjuvant trial period may help identify patients who harbor other sites of distant disease and thus would not benefit from surgery. Outcome Assessment
Using the above criteria, relatively few patients will present with surgically resectable disease confined to the liver alone. In contrast, up to 20% of patients with colorectal metastases may be candidates for liver resection. Furthermore, given the perceived survival advantage of patients with breast cancer metastases undergoing liver resection in retrospective series, it is unlikely that a prospective randomized trial could be successfully conducted. Therefore, the impact of hepatic metastasectomy is difficult to interpret at the present time. Inclusion criteria differ across studies, technical conduct of the procedures (eg, use of ultrasound or radioablative techniques) is not standardized, and chemotherapy has been variably used both before and after surgery. In addition, the use of hormone therapy in women with ER-positive disease is an important factor that could arguably affect both recurrence and survival more than local therapy. Conclusions
Given the existing data, it is reasonable to consider surgical resection of hepatic metastases for breast cancer. However, few patients are good candidates for this procedure. Because of the limitations inherent in observational studies as well as the risks associated with any hepatic resection, it is important to identify those patients most likely to benefit from hepatic metastasectomy. Future efforts must include the establishment of standardized criteria for patient selection, surgical technique, and adjuvant treatment in order to allow comparison across studies.

Disclosures:

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article

References:

1. Fong Y, Cohen AM, Fortner JG, et al: Liver resection for colorectal metastases. J Clin Oncol 15:938-946, 1997.
2. Kato T, Yasui K, Hirai T, et al: Therapeutic results for hepatic metastasis of colorectal cancer with special reference to effectiveness of hepatectomy. Dis Colon Rectum 46:S22-S31, 2003.
3. Weiss RB, Woolf SH, Demakos E, et al: Natural history of more than 20 years of nodepositive primary breast carcinoma treated with cyclophosphamide, methotrexate, and fluorouracil- based adjuvant chemotherapy: A study by the Cancer and Leukemia Group B. J Clin Oncol 21:1825-1835, 2003.
4. Sakamoto Y, Yamamoto J, Yoshimoto M, et al: Hepatic resection for metastatic breast cancer: Prognostic analysis of 34 patients. World J Surg 29:723-727, 2005.
5. Elias D, Maisonnette F, Druet-Cabanac M, et al: An attempt to clarify indications for hepatectomy for liver metastases from breast cancer. Am J Surg 185:158-164, 2003.