Surgical Management of Hepatic Breast Cancer Metastases

Podnos and Wagman provide a comprehensive review of surgical resection for hepatic breast cancer metastases. The authors present the disparate data accrued by various centers in the United States, Europe, and Asia, and then attempt to consolidate these experiences to draw conclusions and provide guidelines. This review is well-written, thorough, and interesting; however, as with any review of a topic devoid of level 1 evidence, the authors raise more questions than answers. While hepatic resection of liver metastases from colorectal and neuroendocrine cancer primaries is accepted therapy[1,2] (despite the absence of randomized data), this is not the case for hepatic spread from most other malignancies, breast cancer included. A minority of patients with other cancers appear to benefit from this approach, but patient selection is haphazard as defined criteria do not exist. An attempt to clarify selection criteria for hepatic resection of metastatic disease from adenocarcinoma of the breast serves both patient and physician, as meaningful discussion of risks and benefits can preclude costly and potentially morbid therapy in patients with persistent disease or early recurrence. Since the time of William Halstead, surgical therapy of primary breast cancer evolved from routine radical resection of the breast, pectoralis musculature, and chest wall to lumpectomy, radiation, and sentinel lymph node biopsy, due to contributions of pioneers like Bernard Fisher and Donald Morton.[3,4] Improved knowledge of anatomy, understanding of patterns of regional and distant spread, and advances in operative technique have allowed many patients to maintain their physical form with less morbidity without compromising survival. Thus, while the operative approach to primary and regional disease becomes less radical, hepatic resection for distant disease seems counterintuitive. Hepatic Resection of Colorectal Cancer Metastases
The basis of hepatic resection for metastases from tumors of the colon and rectum requires an understanding of the difference between "standard of care" and "best common practice." Medical oncologists, surgeons, and most importantly, patients embrace surgical therapy of colorectal cancer liver metastases, although there are no randomized trials demonstrating a statistically significant survival benefit to liver resection over medical therapy or even best supportive care. The natural history of untreated liver metastases from colorectal cancer primaries is approximately 6 months.[5] Treatment with cytotoxic chemotherapy improves survival beyond a year, and the recent addition of biologic agents may extend this further.[6,7] Autopsy studies demonstrate that a substantial population of patients with colorectal cancer primaries die with "liver-only" metastatic disease.[ 5] This is not usually the case with most other cancers. Furthermore, hepatic resection evolved from an approach where "20% of patients died in the operating room because of exsanguinating hemorrhage, [and] another 14% died postoperatively as a direct consequence of enormous blood loss during operation,"[8] to a strategy where operative mortality is approximately 3% in many high-volume centers.[9] In the absence of randomized data permitting a "standard of care" designation, hepatic resection for selected patients with liver spread from colorectal cancer is accepted as "best common practice." As to the benefits of partial hepatectomy for metastases from colorectal cancer primaries, patient and physician must remember that the majority of cancers will recur and those affected will die of disease. In fact, only one-third of patients who develop metastases from cancer of the colon and rectum will have liver-only metastases, one-third of these will be resection candidates, and approximately one-third of these will live at least 5 years, resulting in a measurable benefit for approximately 3,000 individuals.[10,11] Efforts to identify which patients are likely to garner long-term benefit are bountiful and include clinical scoring and imaging criteria.[12,13] This field is evolving, however, as imaging modalities and medical therapies for colorectal cancer have grown beyond the confines of conventional computed tomography scanning and fluorouracil(Drug information on fluorouracil)-based chemotherapy. Hepatic Resection of Metastases From Other Solid Tumors
Apart from metastases of neuroendocrine primaries, hepatectomy for noncolorectal cancer spread is performed infrequently. Podnos and Wagman emphasize selection criteria throughout their analysis, the most important being metastatic disease confined to the liver. While this criterion is met by a third of patients with colorectal cancer primaries, it occurs in only 5% of those with breast cancer primaries.[14,15] Liver metastases from breast cancer, therefore, are frequently a marker for more widespread, metastatic disease; thus, patients with breast cancer liver metastases are more likely to fail with local-only therapy. By contrast, a small cohort of patients appears to derive long-term benefit from the resection of noncolorectal and nonneuroendocrine liver metastases.[16,17] Three questions are raised: What is different about these patients and their tumors, how do we identify them preoperatively, and what can we do to improve results for the others? The first step involves reviewing what evidence already exists, which is what we hope to learn from evaluating personal or institutional series, and then comparing that to data from other centers. Unfortunately, this step often yields confusing results, as demonstrated by the current review. In comparing results from various centers in different countries with different methods of analysis, we are confronted with varying conclusions. For instance, some reports evaluate breast cancer metastases only, while others have included multiple tumor types. Some studies include only unifocal disease, while again, others include all patterns of disease. What follows are conclusions that diseasefree interval from time of treatment of primary, margin status, use of preoperative chemotherapy, abdominal lymph node metastases, and hormone status may or may not have an impact on survival, and thus should or should not guide patient selection. The limi- tations of retrospective analysis are illustrated, especially in areas where sample size is small. Conclusions
Moving forward on this question will require united efforts to accrue meaningful data using the best available criteria-as reiterated by Podnos and Wagman-including limited disease, longer disease-free interval, positive hormonal status, and so forth. Data and tissue should be gathered prospectively. Meaningful gene and tissue array data may be linked with clinical data to identify a subset of responders, as is being done for primary disease. The goal remains the isolation of markers of response, and their translation to better outcomes for all patients.