Rates of axillary nodal recurrence vary between methods of surgical management and whether radiotherapy is used. Early trials in the era of mastectomy and axillary lymph node dissection as treatment for all breast cancer patients, such as the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial, showed rates of regional recurrence that ranged from 4% to 6% for women with negative nodes at their primary operation and 8% to 11% for women with positive nodes at their primary operation after 25 years of follow-up (1). Improvements in systemic and radiation therapy appear to have lowered these rates, as was observed in 2000 by Katz et al. who noted an isolated axillary nodal recurrence rate of 1.2% after adjuvant systemic therapy (median follow-up 116 months) (2). It is also difficult to extrapolate these rates to the modern era, as all the women in these studies underwent axillary dissection, regardless of nodal status.

Similarly, prior to the wide acceptance of sentinel lymph node biopsy, early reports of regional recurrence after breast-conserving therapy showed rates of axillary recurrence of 1% to 3%, with the majority of these occurring in previously unirradiated areas (3,4,5). The retrospective study by Fodor et al. in 1999, in which 894 patients with early-stage breast cancer (49.2% node positive) were observed for axillary recurrence after axillary dissection with either mastectomy or breast-conserving therapy, found that those without irradiation had a 1.2% axillary recurrence rate and those with had a 1.6% rate of axillary nodal recurrence after median follow-up of 120 months (5).

The findings of the NSABP-32 trial, that sentinel lymph node biopsy minimized side effects of surgical axillary staging without compromising regional control or survival (6), ushered in the current era of sentinel lymph node biopsy. However, the wide acceptance of sentinel lymph node biopsy brought new concerns regarding axillary recurrence rates, particularly fears that rates would significantly increase without routine performance of complete axillary lymph node dissection. This has not been the case. A number of studies have examined this question, of which one of the larger retrospective studies is that by Naik et al. in 2004. The investigators of this study included 2,340 patients who were prospectively entered into an institutional database and had undergone sentinel lymph node biopsy with negative sentinel lymph nodes between 1996 and 2003. Median follow-up was 31 months. Of these patients, 81.1% had breast-conserving therapy and 18.9% underwent mastectomy. The total axillary nodal recurrence rate was 0.12%, with 0.04% as a first event, 0.04% occurring coincident with breast recurrence, and 0.04% occurring coincident with distant recurrence (7). Longer follow-up, though, has shown that long-term rates may be higher. The Swedish Multicentre Cohort Study of over 2,000 patients found slightly higher rates of axillary nodal recurrence for those with early-stage breast cancer and negative sentinel lymph node biopsy (8), and the 10-year follow-up study ultimately determined a total axillary recurrence rate of 1.6% as a first, isolated event and an additional 1.0% rate of coincident axillary and breast recurrence (9).

The landmark American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, which included women with T1 or T2 primary tumors and clinically negative nodes undergoing breast-conserving therapy with at least one positive sentinel lymph node on frozen section, initially reported a regional recurrence rate of 0.9% at median follow-up of 6.3 years (10). Long-term follow-up of this study ultimately found a rate of ipsilateral axillary recurrence of 1.5% at 10 years with no significant difference between the sentinel lymph node biopsy and axillary lymph node dissection arms (11). Similar results were also noted in the International Breast Cancer Study Group’s multicenter, randomized, controlled, noninferiority trial examining sentinel lymph node biopsy alone versus axillary lymph node dissection in women undergoing either breast-conserving therapy or mastectomy. Patients who underwent sentinel lymph node biopsy alone and were noted to have micrometastases within
the sentinel lymph node(s) had a 2% axillary failure rate (median follow-up of 9.7 years). When only patients who underwent breast-conserving therapy were included, failure rate was <1%. Those who underwent mastectomy had a 2% axillary failure rate when micrometastases were present (12).

A number of risk factors have been identified that increase the risk of axillary nodal recurrence. Among studies that examine women who underwent axillary lymph node dissection regardless of nodal status, node positivity has emerged as one of the predominant risk factors (in Fodor et al., 0.5% axillary recurrence for node negative vs. 2.8% for node positive, p = 0.0014) (4,5). Age younger than 50 years, estrogen receptor–negative biology, and larger tumor size were also associated with increased risk (4). However, a greater tumor burden in the axilla appears to be a risk regardless of the type of axillary surgical staging, as Houvenaeghel et al. in 2016 found that larger metastases in sentinel lymph nodes were also associated with an increased rate of axillary recurrence (13). This was confirmed by the work of Aalders et al. in 2016, in which 52,626 breast cancer cases from the Netherlands Cancer Registry were evaluated by the investigators. Those staged as N2–3 at primary surgery had a significantly increased risk of axillary recurrence within 5 years (14).