| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Editorial |
Department of Surgery, University of Washington, School of Medicine/Seattle Cancer Care Alliance, 1959 N.E. Pacific Street, Box 356410, Seattle, Washington 98195
Correspondence: Address correspondence and reprint requests to: Benjamin O. Anderson, MD, FACS; E-mail: banderso{at}u.washington.edu.
For most of the 20th century, surgeons believed axillary lymph node dissection (ALND) to be a therapeutic procedure for breast cancer, according to Halsted’s notion that breast cancer metastasizes in series from the breast to the nodes and then from the nodes to distant organs.1 The ALND was thought to limit malignant spread by eliminating a critical pathway for cellular migration from the breast to distant sites. On the basis of the rationale that "bigger must be better," surgeons considered the adequacy of their ALND to be measured by the degree to which the dissected axilla was left devoid of lymphatic and adipose tissue.2 Considered a necessary evil of proper surgical cancer care, lymphedema was largely ignored by the surgical community. This conceptual framework, while intellectually plausible, proved to be biologically flawed.
Bernard Fisher3 in the United States and Umberto Veronesi4 in Europe led the groundbreaking randomized trials that have unequivocally proven breast-conserving surgery to be equally effective to more extensive breast cancer resections in the reduction of breast cancer mortality. The breast-conservation trials were initially rejected by surgeons as counterintuitive and dangerous, because everyone "knew" that patients should undergo cancer surgery as soon as possible and with the largest feasible resection, "before the cancer spreads."2 As surgeons gradually came to accept breast conservation, a new paradigm evolved in cancer biological thinking. It became obvious that cancers metastasize, not in series through the nodes to distant sites, but rather in parallel to the nodes (via lymphatics) and to distant organs (via the circulation). Realizing that hematogenous micrometastasis occurs early in the course of the disease, Fisher came to describe breast cancer as a fundamentally systemic disease.5
In line with the shifting biological paradigm, Fisher and others questioned the value of ALND other than for the purposes of cancer staging.6,7 Since then, the role of the ALND has been debated extensively, and no definite winner has been declared.8 ALND advocates have argued that lymphadenectomy still has therapeutic benefit for breast cancer patients because ALND facilitates regional control of axillary disease.9–11 Supporters contend that surgical extirpation of microscopic nodal metastases is curative without adjuvant chemotherapy in a subset of patients.12 Conversely, ALND dissenters maintain that overall survival, depending on the development of distant metastases, is not influenced by ALND in most patients. These opponents suggest that patients with microscopic axillary metastases can be cured by adjuvant chemotherapy, nodal irradiation, or both, without axillary dissection.13,14
The debate regarding the therapeutic benefit of ALND was rekindled with more recent reports based on Surveillance, Epidemiology, and End Results data suggesting that the number of removed nodes is associated with crude survival in patients with no or one to three positive nodes15 and that in node-negative patients, examination of fewer nodes is associated with an increased risk of death due to breast cancer.16 These studies stirred controversy because they appeared to conflict with Fisher’s paradigm and seemed to suggest that ALND may indeed have a therapeutic benefit, even in patients with negative axillary lymph nodes.
In this issue of Annals of Surgical Oncology, Schaapveld and colleagues performed a population-based study to examine how the number of examined axillary lymph nodes in a nodal dissection specimen relates to overall mortality. Between 1994 and 1999 in the North Netherlands, 5314 consecutive breast cancer patients underwent mastectomy or breast-conserving surgery and ALND.17 In this statistically sophisticated epidemiological analysis, the authors reaffirm Fisher’s paradigm that ALND does not itself prevent the systemic spread of disease. These researchers found that the association between fewer nodes dissected and worsened outcome can be explained by (1) migration of stage among node-positive patients, because patients with fewer dissected nodes are more likely to be understaged, and (2) age at surgery, because surgeons tend to perform more limited node dissections among elderly people who have a more limited crude, but not disease-specific, survival. After adjustment for age, tumor size, number of positive nodes, and method of cancer detection, the number of examined axillary nodes is no longer associated with relative survival from breast cancer. Restated, removing fewer axillary lymph nodes in an ALND does not lead to more breast cancer deaths.
While the Schaapveld study reaffirms that the removal of normal axillary nodes has no therapeutic benefit, a key surgical question remains. The presence of nodal metastases is the single most important independent variable for predicting prognosis. If prognostic information regarding an individual cancer can be obtained in some other way, e.g., genetic profiling of the primary tumor, then will axillary staging become obsolete? If the presence of lymphatic metastases is only a marker of biological metastatic potential, then it may be that metastatic nodes can be relegated to systemic and radiotherapy without surgical resection. On the other hand, we may find that removal of cancer-bearing lymph nodes may be necessary for long-term cancer control, at least in a subset of patients.
The National Surgical Adjuvant Breast Project (NSABP) pioneered the testing of boundaries regarding what can be done or omitted in breast cancer surgical therapy. If breast cancer were a purely systemic disease, then locoregional control with surgery could become unimportant and anachronistic. The NSABP tested this hypothesis in the NSABP-B17 trial of ductal carcinoma-in-situ by having minimal requirements for the attainment of adequate surgical margins. While mortality was unaffected, they found that inadequate surgical margins remained an independent predictor of local recurrence in the breast, even in the face of radiotherapy.18 Since that time, surgical margins have remained a core measure for the adequacy of breast cancer resection.19 By virtue of pushing the scientific limits of surgical resection, the NSABP has proven that there is indeed a lower limit below which surgeons should not go in providing adequate removal of tissue in the breast.
Although there is no benefit in removing histologically normal lymph nodes, it remains unknown whether cancer-bearing axillary lymph nodes can be left unresected without adverse consequences to the patient. Sentinel node mapping has made major inroads by permitting axillary staging without the performance of a completion ALND in the great majority of node-negative breast cancer patients. However, we still do not know whether a completion ALND provides therapeutic benefit among sentinel node–positive patients. This question would have been answered by the American College of Surgeons Oncology Group Z0011 trial led by Armando Guiliano, in which women who had positive sentinel nodes were randomized to receive or not receive completion ALND.20 Sadly, the trial failed to accrue enough patients to meet recruitment criteria and was suspended.
Modern surgeons were diametrically divided on the value of the American College of Surgeons Oncology Group Z0011 trial, much as their predecessors were about breast conservation. Some were convinced that ALND has little or no therapeutic benefit beyond its role in cancer staging and, therefore, is a fundamentally unnecessary and morbid procedure. Others thought that surgical extirpation is critical to control grossly measurable regional disease among node-positive patients, believing that grossly measurable cancer in the nodes will remain uncured in a significant subset of patients. Like 20th century surgeons debating the merits and risks of breast conservation, modern surgeons were divided in their beliefs based on incompletely tested conceptual biases regarding the biological behavior of breast cancer. Unlike 20th century surgeons whose questions were answered by Fisher, Veronesi, and others, modern surgeons may never learn the true value of completion ALND, having lost the chance to test the hypothesis in a large randomized trial. This opportunity may not come our way again.
Received for publication September 1, 2005. Accepted for publication September 8, 2005.
REFERENCES
This article has been cited by other articles:
 |
|
 |
|
  J. E. Gervasoni Jr., S. Sbayi, and B. Cady Role of lymphadenectomy in surgical treatment of solid tumors: an update on the clinical data. Ann. Surg. Oncol., September 1, 2007; 14(9): 2443 - 2462. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
