Surgical Management of Hepatic Breast Cancer Metastases
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
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
Hepatic Resection of Colorectal
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. 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," to a strategy where operative mortality is approximately 3% in many high-volume centers. 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-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.
2. National Comprehensive Cancer Network: Colon and Rectal Cancer Treatment Guidelines for Patients. Boston, Jones and Bartlett, 2005.
3. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233-1241, 2002.
4. Morton DL, Thompson JF, Essner R, et al: Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: A multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg 230:453-465 (incl discussion), 1999.
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6. Goldberg RM, Sargent DJ, Morton RF, et al: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23-30, 2004.
7. Hurwitz H, Fehrenbacher L, Novotny W, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-2342, 2004.
8. Foster JH, Berman MM: Solid liver tumors. Major problems in clinical surgery. Major Probl Clin Surg 22:1-342, 1977.
9. Jarnagin WR, Gonen M, Fong Y, et al: Improvement in perioperative outcome after hepatic resection: Analysis of 1803 consecutive cases over the past decade. Ann Surg 236:397-406, 2002.
10. Scheele J, Stangl R, Altendorf-Hofmann A, et al: Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 110:13-29, 1991.
11. Fong Y, Cohen AM, Fortner JG, et al: Liver resection for colorectal metastases. J Clin Oncol 15:938-946, 1997.
12. Fong Y, Fortner J, Sun RL, et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230:309-318, 1999.
13. Jamison RL, Donohue JH, Nagorney DM, et al: Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg 132:505-510, 1997.
14. Hoe AL, Royle GT, Taylor I: Breast liver metastases—incidence, diagnosis and outcome. J Roy Soc Med 84:714-716, 1991.
15. Patanaphan V, Salazar OM, Risco R: Breast cancer: Metastatic patterns and their prognosis. South Med J 81:1109-1112, 1988.
16. Harrison LE, Brennan MF, Newman E, et al: Hepatic resection for noncolorectal, nonneuroendocrine metastases: A fifteen-year experience with ninety-six patients. Surgery 121:625-632, 1997.
17. Weitz J, Blumgart LH, Fong Y, et al: Partial hepatectomy for metastases from noncolorectal, nonneuroendocrine carcinoma. Ann Surg 241:269-276, 2005.