A brief history of Axillary Management

William Halsted proposed the radical mastectomy for the treatment of primary breast cancer, wherein the breast, pectoralis muscles, and ipsilateral axillary nodes were extirpated en bloc.  Thus, breast cancer surgery was closely intertwined with axillary lymph node surgery. Within a few years after widespread implementation of the Halsted radical mastectomy, it became evident that approximately 30% of women who were node-negative at the time of surgery ultimately succumbed from metastatic breast cancer.  This observation was inconsistent with the Virchow-Halsted hypothesis for the centrifugal spread of breast cancer from a primary tumor focus, and alluded to the existence of alternate pathways for distant spread of the disease.  In the 1970s, two large randomized trials (the Kings/Cambridge trial in the UK and the National Surgical Adjuvant Breast and Bowel Project (NSABP)-04 trial in the USA were launched to test the tenets of the Virchow-Halsted hypothesis.  These trials randomized patients with a clinically node-negative axilla to either early or delayed treatment of the axilla (with either surgery or radiotherapy).  The delayed treatment of the axilla did not adversely affect outcome, suggesting that axillary lymph node metastases was not the primary source for distant spread of breast cancer, and alternate means of dissemination (perhaps hematogenous) were responsible for poor outcomes.

Yet, despite the results of the Kings/Cambridge and NSABP-04 trials, complete axillary lymph node dissection (ALND) remained an integral component of the surgical treatment of early breast cancer until the late 20^th century.  There were two reasons for the enduring relevance of ALND.  First, in patients with clinically node-negative breast cancer, failure to treat the axilla with either surgery or radiotherapy could substantially increase the risk of axillary recurrence, some cases of which were uncontrolled and severely impaired quality of life.  Secondly, adjuvant systemic therapy was widely implemented for the treatment of breast cancer in the 1980s, and the absolute benefit of adjuvant systemic therapy was greater for patients with node-positive than node-negative breast cancer.  Thus, until the late 20^th century, nodal status was vital for the adjuvant systemic therapy decision-making process.  However, in more recent years, decisions concerning administration of adjuvant systemic therapy have been increasingly predicated upon tumor biomarkers (i.e., estrogen receptor (ER), progesterone receptor (PR), and HER-2 neu status).

Since the mid-1990s, there has been a de-escalation in the use of axillary surgery.  Two randomized trials examined the effect of omitting axillary surgery altogether in elderly breast cancer patients, the International Breast Cancer Study Group (IBCSG) Trial 10-93 and an Italian trial.  Both trials showed that breast cancer survival and overall mortality did not differ between the “axillary surgery” and “no axillary surgery” groups in elderly patients, with better quality of life in the “no axillary surgery” group.   Also in the late 1990s, the sentinel lymph node biopsy (SLNB) concept was introduced, whereby the first lymph nodes in the axillary basin to receive drainage from the breast (i.e. the sentinel lymph nodes) were identified with either radiotracer, blue dye, or use of both agents.  If the sentinel nodes harbor malignancy, then additional nodes in the axillary basin may as well, and complete axillary dissection is undertaken.  On the other hand, if there is no evidence of metastasis in the sentinel nodes, then further axillary surgery is avoided.  At least seven trials randomized clinically node-negative breast cancer patients to either the SLNB policy versus standard ALND.  These trials consistently showed that morbidity is lower and quality of life better in patients who undergo SLNB compared to standard ALND, with no adverse effects on survival.

More recently, four trials, the American College of Surgeons Oncology Group (ACOSOG) Z0011, After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS), International Breast Cancer Study Group (IBCSG) 23-01, and AATRM (Spanish), have randomized sentinel node-positive patients to either no further local therapy of the axilla versus completion ALND or radiotherapy to the axilla.  Each of these was a non-inferiority trial, and found that avoidance of further axillary surgery in sentinel node-positive patients was not worse than completion ALND or axillary radiotherapy.  These trials seem to suggest that a residual low burden of axillary disease can be safely treated with adjuvant systemic therapy and/or radiotherapy.

Neo-adjuvant systemic therapy may result in substantial down-staging of breast cancer.  Until recently, there was reluctance to avoid complete ALND in patients following administration of neo-adjuvant systemic therapy, but there is now evidence that SLNB policy can be applied to these patients as well.  For node-positive patients who convert to node-negative status, careful identification and evaluation of the sentinel nodes may potentially obviate the need for completion ALND and thereby reduce the morbidity of axillary surgery.

Finally, there are now trials underway to examine the possibility of avoiding axillary surgery altogether (also avoiding SLNB) in clinically node-negative patients with favorable tumor characteristics.  These patients generally have either no disease in the axillary nodes or a low burden of disease that can be safely treated with adjuvant systemic therapy and/or radiotherapy.  In these patients, biomarkers are utilized to determine eligibility for adjuvant systemic therapy.  Thus, the surgical management of the axilla continues to evolve, with the aim of improving both local control of the axilla and quality of life.

John Benson, November 2024