How Many Nodes Are Enough? The Breast Surgeon’s Dilemma

Abstract

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. 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. 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 Fisher in the United States and Umberto Veronesi in Europe led the groundbreaking randomized trials that have unequivocally proven breastconserving 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.’’ 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. In line with the shifting biological paradigm, Fisher and others questioned the value of ALND other than for the purposes of cancer staging. Since then, the role of the ALND has been debated extensively, and no definite winner has been declared. ALND advocates have argued that lymphadenectomy still has therapeutic benefit for breast cancer patients because ALND facilitates regional control of axillary disease. Supporters contend that surgical extirpation of microscopic nodal metastases is curative without adjuvant chemotherapy in a subset of patients. 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. 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 nodes and that in node-negative patients, examination of fewer nodes is associated with an increased risk of death due to breast Received September 1, 2005; accepted September 8, 2005; published online January 30, 2006. Address correspondence and reprint requests to: Benjamin O. Anderson, MD, FACS; E-mail: banderso@u.washington.edu.