Breast Cancer
Advances in locoregional and systemic therapy allow for a potential cure of patients with early-stage breast cancer, but for patients with metastatic breast cancer the treatment is often one of palliation. Approximately 50% of breast cancer patients develop distant metastases; these commonly involve the bones, liver, lung, and/or brain.[30,31] The prognosis for such patients is poor, with a 5-year survival of 23.4%, as demonstrated by Howlader et al in their review of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database.[32] As many as 50% of patients with stage IV disease develop liver metastases, with an associated median survival ranging from 3 to 15 months.[33-35] Liver metastases are present in 15% of patients with newly diagnosed metastatic breast cancer, and the liver is the only site of distant disease in one third of these patients.[36,37] Due to the frequency of chemoresistance and the negative hormone receptor status of most liver metastases, the response to systemic therapy is often limited, such that durable complete responses are infrequent.[38]
Significant progress has been made in the multimodality treatment of patients with breast cancer; advances include the use of more effective chemotherapy (anthracyclines and taxanes), antihormonal therapy (aromatase inhibitors), and directed biologic agents (trastzumab [Herceptin]). Nonetheless, the development of distant metastasis continues to be associated with a very poor prognosis.[39] Despite the limitations of systemic therapy, local treatment options for managing hepatic metastases are still rarely considered. The reasons for this include the common occurrence of extrahepatic metastases,[40] which have traditionally been a contraindication to hepatic resection, and the overall poor prognosis of patients with breast cancer–related liver metastases.
Hepatectomy for metastatic breast cancer: a review of the literature
Data Review of Modern Liver Metastasectomy Series for Breast Cancer
A number of reports have been published evaluating the role of hepatic resection for metastatic breast cancer in highly selected patients. Most recently, Chua et al authored a review of hepatic resection for metastatic breast cancer, evaluating published studies reporting outcomes of breast cancer–related hepatectomy between January 2000 and January 2010; these studies were analyzed for safety, efficacy, and prognostic factors associated with survival.[41] In total, 19 studies were reviewed, in which 533 patients were identified who underwent hepatectomy for breast cancer–related metastasis. The median time from primary tumor to development of liver metastasis was 40 months (range, 23 to 77 months). Median overall survival was 40 months, with a median 5-year survival of 40% (range, 21% to 80%). The median postoperative mortality rate was 0% (range, 0% to 6%). The prognostic factors of R2 surgical resection and hormone-refractory disease were associated with worse outcomes.
Much as with melanoma, the majority of studies of breast cancer–related hepatic resection are relatively small. The largest series, by Adam et al, reviewed 85 consecutive patients with breast cancer liver metastasis treated with hepatic resection between 1984 and 2004.[42] In this study, because of improved outcomes following hepatic resection, no mortality was seen within 60 days of surgery. R0 surgery was achieved in 66 patients and R1 surgery in 15 patients. Median survival was 32 months, and 5-year overall survival was 37%. For 59 patients who developed metastatic disease following hepatic resection, the median time to recurrence was 10 months. Of this subgroup, 31 patients developed extrahepatic or intra- and extrahepatic recurrences. For patients with disease limited to the liver (n = 12), repeat hepatectomy was performed. Multivariate analysis revealed that factors associated with worse outcomes included poor response to preoperative chemotherapy (5-year overall survival, 0% to 10%), R2 surgery (5-year overall survival, 10%), and inability to undergo repeat hepatectomy due to extrahepatic disease (5-year overall survival, 29%).
Elias et al reported similar findings in their experience with hepatic resection in 54 patients with metastatic breast cancer between 1986 and 2001.[43] Major hepatic resection (> 3 segments) was performed in 32 patients, with 20 patients undergoing a right hepatectomy. R0 surgery was achieved in 44 patients. Median survival was 34.3 months, and 5-year overall survival was 34%—results comparable to those of Adam et al. Disease-free interval for liver recurrence was 16 months, with only 5 of 30 recurrences occurring in bone, lung, or brain first. Multivariate analysis revealed that only hormone receptor status (P = .03) influenced survival, with the risk of death increased 3.5-fold when status was negative.
Additional studies by Hoffmann and Thelen, though small, have shown a similar benefit for hepatic resection for metastatic breast cancer.[44,45] With minimal surgical mortality, hepatic resection achieved a 5-year survival of 42% to 48% in selected patients with stage IV breast cancer. Poor prognostic factors included positive resection margins and disease-free interval between the treatment of the primary tumor and the diagnosis of hepatic metastasis < 1 year (Table 2).
Therapeutic Agents
Mentioned in This Article
Carboplatin(Drug information on carboplatin)
Cisplatin
Dacarbazine
Fotemustine
Interleukin-2
Ipilimumab (Yervoy)
Paclitaxel
Temozolomide(Drug information on temozolomide) (Temodar)
Trastuzumab(Drug information on trastuzumab) (Herceptin)
Vemurafenib (PLX4032; Zelboraf)
Brand names are listed in parentheses only if a drug is not available generically and is marketed as no more than two trademarked or registered products. More familiar alternative generic designations may also be included parenthetically.
Conclusion
Surgical indications for patients with stage IV disease processes are expanding. With advances in surgical technique and perioperative care, the morbidity and mortality of patients undergoing hepatic resection have declined dramatically over the last two decades. As minimally invasive techniques become more widespread, the associated surgical morbidity can be anticipated to diminish further. These improvements have allowed surgery to be reincorporated into the multimodal treatment of advanced disease processes, including metastatic melanoma and breast cancer.
Surgical resection of hepatic metastases in the setting of stage IV melanoma and breast cancer has been clearly associated with long-term survival. Prognostic factors including completeness of surgical resection, prolonged disease-free interval, low multiplicity of metastases, and no or limited extrahepatic disease give insight into the patients who would be most likely to benefit from surgical resection. Improving the methods by which we stratify patients in whom surgical resection will be an optimal treatment is imperative. As systemic therapies improve, an increased role for surgical resection will follow in treating patients with previously untreatable disease.
Financial Disclosure: 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.
