Targeted axillary dissection

INTRODUCTION — Nowadays, neoadjuvant systemic therapy (NST) is given to a substantial proportion of patients with primary breast cancer, including those with clinically node-positive (cN+) disease at diagnosis [1,2]. After NST, axillary pathologic complete response was achieved in approximately 60 percent of patients with human epidermal growth factor receptor 2 (HER2) positive (HER2+) tumor subtype and in 45 percent of patients with triple-negative breast cancer [3]. In NST-responsive patients, tumor deposits in axillary lymph nodes are downsized or cleared, potentially rendering these patients eligible for less invasive procedures than a full axillary lymph node dissection [4]. At the same time, alternative surgical approaches must not compromise oncologic safety [5]. In addition, the correct determination of axillary status after NST is an important part of post-NST treatment strategy. The axillary lymph node status after NST has prognostic value [6,7], and guides, in combination with other clinical factors, the extent of axillary radiotherapy and postneoadjuvant systemic therapy [8-10].

First described in 2014, a procedure called targeted axillary dissection (TAD) supplements sentinel lymph node biopsy with the resection of the pre-NST marked, metastatic lymph node(s) (targeted lymph node) [11]. The indications, techniques, technical performance, and clinical outcomes of TAD are discussed in this topic. Other methods of axillary staging, either before or after NST, can be found in other topics. (See "Overview of management of the regional lymph nodes in breast cancer" and "Overview of sentinel lymph node biopsy in breast cancer".)

AXILLARY MANAGEMENT AFTER NEOADJUVANT CHEMOTHERAPY — After patients undergo neoadjuvant systemic therapy (NST), the axilla should be reevaluated with clinical examination and possibly a repeat ultrasound after its completion. The information gathered by the axillary assessments prior to and after NST should inform the choice of axillary surgery. Besides axillary lymph node dissection (ALND), less invasive surgical options include sentinel lymph node biopsy (SLNB) alone, targeted lymph node biopsy (TLNB) alone, and TAD (ie, SLNB plus TLNB), among others.

Surgical options — In a 2022 survey by the European Breast Cancer Research Association of Surgical Trialists, the most common post-NST axillary surgery in patients with cN1 disease converting to ycN0 was TAD (54.2 percent), followed by SLNB alone (20.9 percent), level 1 to 2 ALND, (18.4 percent), level 1 to 3 ALND (4 percent), and TLNB (2.5 percent) [12].

●Axillary lymph node dissection – Complete ALND was the standard procedure in clinically node-positive (cN+) patients for a long period of time [13]. However, ALND is associated with several morbidities [14], and its application might not be justified in patients who converted to a clinically node-negative (ycN0) or pathologically node-negative (ypN0) axilla after NST. Therefore, less invasive approaches have been evaluated during the past couple of years [15,16].

●Sentinel lymph node biopsy – SLNB is a well-established procedure in ycN0 patients but has presented with unacceptable false-negative rates (FNRs) of more than 10 percent (versus ALND) after NST in cN+ patients. The FNR could be improved to well below 10 percent when at least three sentinel lymph nodes (SLNs) were retrieved after NST [17,18]; however, in clinical routine management less than three SLNs are obtained in a considerable proportion of patients [19,20].

●Targeted lymph node biopsy – TLNB entails tagging biopsy-proven metastatic lymph node(s) before NST and removing these targeted lymph nodes (TLNs) after NST [21]. The TLN is the most abnormal or one of the suspicious axillary lymph node(s) that was biopsied and marked before the initiation of NST [22]. Therefore, in some instances the TLN is also called the marked lymph node (MLN) [15]. Although the marking and identification of the TLN may also apply to upfront surgery followed by adjuvant therapy [23], the concept of TAD generally applies to patients undergoing NST.

●Targeted axillary dissection – TAD usually takes place after the end of NST, during which both the SLNs and TLNs are excised in one surgical session [11]. While in most clinical studies TAD was only regarded as successful when both SLN(s) and the TLN were resected [20], in some investigations a few patients without SLNs [22,24] or TLN (MLN) [24] were still considered for the evaluation of the feasibility of TAD.

Clinical guidelines — There is no consensus on axillary management after NST in patients with cN+ breast cancer. (See "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla'.)

Clinically node-positive after NST — It is generally agreed that patients who present with clinically persistent nodal disease after NST (ycN+) should undergo ALND [10,25].

Clinically node-negative after NST — Although available clinical guidelines present partly overlapping criteria, there is no international consensus yet on the axillary surgical management in cN+ patients who convert to ycN0 [26]. In general, TAD without ALND should be reserved for patients with both ycN0 and ypN0 status after NST. Further restrictions vary per guidelines:

●The National Comprehensive Cancer Network (NCCN) guidelines endorse TAD without ALND in patients who convert from cN+ to ycN0, undergoes SLNB with a dual tracer, which removes at least three SLNs along with the pre-NST clipped metastatic lymph node [10].

●The guidelines of the European Society for Medical Oncology (ESMO) list similar criteria, although they restrict the use of TAD to patients with ipsilateral level I or II metastatic lymph nodes (cN1 [27]) at diagnosis [28].

●The German guidelines from the Arbeitsgemeinschaft Gynäkologische Onkologie suggest that TAD alone (or ALND) is only indicated in patients with cN1 involvement pre-NST and ycN0 status [25,29]. If the TLN cannot be identified after NST, patients should undergo ALND, unless local practice is different.

TECHNICAL PERFORMANCE — Since the first data on feasibility and accuracy of sentinel lymph node biopsy (SLNB), targeted lymph node biopsy (TLNB) and TAD in clinically node-positive (cN+) patients after neoadjuvant systemic therapy (NST) were published in 2016 [22], a good number of similar investigations followed that were evaluated in a few reviews and meta-analyses published between 2019 and 2022 [15,16,30-32]. Of note, the majority of data were obtained from nonrandomized single-center studies, except for one prospective study that was conducted at 50 study centers [20].

Identification rate — The identification rate (IR) is simply the success rate of identifying the intended lymph node(s) with each procedure. It is usually the first technical outcome that is tracked with any axillary staging procedure.

Sentinel lymph node biopsy — The IR of SLNB in cN+ breast cancer patients after NST has been reported to be approximately 90 percent in several individual studies (eg, 92.9 percent [19], 93.2 percent [33], 90 percent [20]) and in two meta-analyses (90 percent [18], 91 percent [17]), although with some heterogeneity among studies.

Targeted lymph node biopsy — A pooled analysis of 1430 patients recruited in 17 clinical studies demonstrated successful excision of the marked target lymph node (TLN) in 90 percent of patients (95% CI 85.1-95.1) [15]. A meta-analysis, published one year later in 2022, reported an intraoperative IR of 93.5 percent (95% CI 90.1-96.2 percent) in 1920 patients from 30 clinical studies [32]. In a prospective study including 50 study centers, it was shown that the IR in those that perform more than 20 TLNB procedures was higher than IR in other centers (89 versus 69 percent) [20]. The IR also differs between TLN marking and localization techniques (see 'Marking and localization of targeted lymph nodes' below):

●The IR of TLNB after clipping the TLN was 91.7 percent (95% CI 87.3-95.4) obtained from 24 studies [32], and 88 percent in another pooled analysis of 703 procedures [34]. Intraoperative retrieval of the clipped TLN is complicated when the clip cannot be visualized prior to surgery [35].

●The IR of the TLNB after tattooing the TLN (seven studies) was 97.1 percent (95% CI 89.1-100) and slightly higher than the IR for the marking axillary lymph nodes with radioactive iodine seeds (MARI) procedure (five studies) with 95.6 percent (95% CI 91.2-98.7).

●The IR of TLNs localized with a magnetic seed either prior to or after NST was 100 percent [36,37], similar to the IR of the radiofrequency identification device LOCalizer, which was evaluated in a pilot study [38]. Radar reflector localization with SAVI SCOUT was successful in 97 percent of patients [39].

Targeted axillary dissection — The IR of TAD should be improved over SLNB alone (approximately 90 percent [17,18]) as the TLN is identical to a sentinel lymph node (SLN) in >60 percent of TAD procedures and this lymph node could undergo dual or triple marking as a result of TLN (eg, clip) and SLN (eg, technetium 99m, blue dye) marking.

The intraoperative IR of the MARI procedure combined with SLNB was 98.2 percent in 227 patients [40]. TAD was successful in 199 of 229 patients (86.9 percent; 95% CI 81.8-91) with initially clipped TLNs followed by guide-wire localization [20].

False-negative rate — The false-negative rate (FNR) is determined by comparing the ypN status of TLN(s) or TAD lymph nodes with the ypN status of lymph nodes obtained by axillary lymph node dissection (ALND). When TLN or TAD lymph nodes are pathologically node-negative (ypN0) but at least one other axillary lymph node is pathologically positive, then TLNB or TAD is considered false negative [15,20,32].

Sentinel lymph node biopsy — In a 2021 meta-analysis of 3578 cN+ study participants in 27 clinical studies, the pooled FNR was 15 percent [17], similar to the FNR of 14 percent in a meta-analysis from 2018 [18]. In four clinical studies, the combined FNR of SLNB could be reduced from 19 percent with a single tracer to 11 percent by mapping with dual agents [18]. Dual mapping is recommended in some clinical guidelines [10], but not in others [25,29].

Targeted lymph node biopsy — In the German multicenter SenTa study, the FNR in 203 patients who underwent clipping and wire-guided localization of the TLN followed by ALND was 7.2 percent (95% CI 3.1-13.6) [20]. TLNB based on localization of the clipped TLN with an iodine-125 seed resulted in five false negatives out of 120 procedures (4.2 percent; 95% CI 1.4-9.5). An analysis of 366 patients from nine clinical studies yielded a pooled FNR of 6.28 percent (95% CI 3.98-9.43) [15]. In a meta-analysis of 847 patients, the FNR was 5.5 percent (95% CI 3.3-8) [32]. The MARI procedure, which does not include SLNB, exhibited a FNR of 7 percent [41].

Targeted axillary dissection — The first publication for TAD in 2016 presented with a FNR of 1.4 percent, while the FNR of SLNB in the same study was 10.1 percent [22]. This generated a lot of interest among breast surgeons and led to the initiation of numerous similar investigations.

The pooled FNR of 521 TAD procedures in 13 studies was 5.18 percent (95% CI 3.41-7.54) [15], similar to the FNR of 6.3 percent (95% CI 3.2-10.1) in a meta-analysis of nine studies [32]. Several studies have presented with FNRs of <5 percent [20,22,42], one even with a FNR of 0 percent [36], thereby considerably improving the FNR of SLNB alone.

The use of immunohistochemistry (IHC) as opposed to hematoxylin and eosin staining alone in histopathologic analysis of TAD lymph nodes could improve the FNR of TAD by detecting small micrometastases or isolated tumor cells. In previous studies, though, IHC was not routinely applied [20,22]. This suggests that, in theory, the FNR of TAD could even be improved when IHC is used.

Ongoing clinical studies serve to bridge several knowledge gaps related to TAD. For example, more evidence regarding IR and FNR is being collected (ClinicalTrials.gov ID: NCT03630913, NCT04998682, NCT05763641).

Complications — No procedural complications or adverse events related to the initial marking, localization, or retrieval of the TLN have been reported in clinical studies of TLNB or TAD, regardless of the technique used [36,37,43-46]. SLNB alone has proven to cause fewer complications such as arm or shoulder pain or lymphedema compared with SLNB plus ALND [47-49]. A comparison of complications experienced with TAD alone versus TAD followed by ALND has not been published yet, but data are expected to arise from ongoing studies [26].

CLINICAL OUTCOMES — Limited clinical outcome data show that in selected patients undergoing neoadjuvant systemic therapy (NST) for clinically node-positive (cN+) breast cancer, a de-escalated axillary surgical procedure (eg, TAD or marking axillary lymph nodes with radioactive iodine seeds [MARI]) without axillary lymph node dissection (ALND) appears oncologically safe.

●In 353 consecutive patients treated for cN1-3 (83.5 percent cN1) disease in China, 85 underwent TAD alone, 152 TAD plus ALND, and 85 ALND. Three-year freedom from nodal recurrence rate was 100 percent in the TAD group and 98.7 percent in the ALND with or without TAD group with pathologic complete response in the axilla (p = 0.29). Two patients (2.3 percent) in the TAD group developed distant metastases [50].

●In a combined evaluation of 785 patients from 19 international centers (cN1-3, 95 percent cN1, 100 percent ypN0) who had undergone either sentinel lymph node biopsy (SLNB; n = 565) based on dual tracer mapping or TAD (n = 220), five-year axillary recurrence rate was 1.1 percent, locoregional recurrence rate was 3.1 percent, and invasive recurrence rate was 10 percent [51]. No axillary recurrence had occurred in the TAD group two years after surgery, as opposed to five patients in the SLNB group (p = 0.19). The low five-year axillary and locoregional recurrence rates obtained in this pathologically node-negative (ypN0) cohort are consistent with previous publications that presented with five-year axillary recurrence rates of 0 percent [52] or 1.1 percent [49], and 10-year axillary recurrence rate of 1.6 percent [53] after SLNB alone.

●In another study of 176 cN+ patients treated in Brazil, the metastatic lymph node was marked pre-NST with a 4 percent carbon suspension and resected in combination with sentinel lymph nodes (SLNs) at the time of surgery [54]. When at least one of the retrieved lymph nodes was positive, ALND was performed. Follow-up data were presented for 168 patients; however, no distinction was made whether TAD alone or TAD plus ALND was applied, thereby limiting the meaningfulness of these results. Five axillary (2.9 percent, none in the TAD group), 7 local (4.1 percent), and 28 distant recurrences as well as 10 deaths occurred, accounting for disease-free survival of 83.3 percent and overall survival of 94 percent.

●In a retrospective analysis of 272 patients who underwent MARI (with or without axillary radiotherapy, with or without ALND), the recurrence rate was 9.9 percent for the entire cohort and the three-year axillary recurrence-free interval was 98 percent (95% CI 96-100) [55].

●The SenTa study is a prospective registry study conducted in Germany. A total of 182 patients had one to three suspicious lymph nodes; 119 received TAD alone and 80 received TAD with ALND [56]. Unadjusted invasive disease-free survival was 82 percent in the TAD with ALND group and 91 percent in the TAD alone group; axillary recurrence rates were 1.4 and 1.8 percent, respectively. Adjusted multivariate Cox regression indicated that TAD alone was not associated with an increased risk of recurrence or death.

Ongoing large randomized (NCT04109079) and nonrandomized (NCT04373655) studies should generate better data about patient-reported outcomes and clinical outcomes.

CONTROVERSIAL ISSUES — TAD is a new procedure. As such, the clinical practice has not been standardized, and several controversial issues remain:

●While TAD is a fine technique, it is not the only accepted surgery for axillary staging after neoadjuvant chemotherapy. As stated above, sentinel lymph node biopsy (SLNB) alone may achieve an adequate false negative rate (FNR) when using dual tracers and recovering at least three sentinel nodes [17,18]. Some institutions do not have a wireless means of marking the lymph nodes, and there is currently controversy regarding the importance of clipping a node (especially given that they are not always found intraoperatively [57]). Furthermore, the value of reducing the FNR remains in question as residual nodal disease after SLNB does not directly translate into a higher locoregional recurrence rate in the Z11 trial [58]. Nevertheless, in order to indicate postneoadjuvant or adjuvant treatment strategies, an adequate staging of the axilla is necessary. Finally, there are trials evaluating eliminating surgery altogether in patients treated with neoadjuvant chemotherapy who have an imaging/core-needle biopsy complete response [59]. Thus, this area of breast cancer treatment is actively evolving. Whether TAD eventually becomes the standard of care or is replaced by another technique or approach of axillary staging after neoadjuvant chemotherapy remains to be seen.

●While most agree that TAD can be used in cN1 patients after neoadjuvant systemic therapy (NST), whether TAD is appropriate for more extensive nodal disease (cN2-3) is controversial. In a prospective registry, 85 patients with cN1-3 breast cancer underwent TAD. The FNR in the whole cohort was 12.2 percent (95% CI 5-19.4), while it was 6 percent (95% CI 1-11.8) in patients with limited nodal involvement (cN1) [50].

●In addition, there is currently no consensus on how many suspicious lymph nodes should be marked in patients with more than one suspicious lymph node [60,61]. In the majority of cases, one TLN was marked [20,24], but in some evaluations two, three, or more than three lymph nodes were marked [62]. Based on the analysis of 14 patients with one to three clinically suspicious lymph nodes at diagnosis, it was shown that the FNR of targeted lymph node biopsy was reduced from 7.1 to 0 percent when two instead of one TLN were marked [63]. In the ongoing SenTa 2 study, the FNR of TAD is evaluated in patients with ≥3 suspicious lymph nodes at presentation and axillary pathologic complete response after neoadjuvant systemic therapy (NCT05462457).

●Furthermore, it is not clear if the molecular subtype influences the accuracy of TAD. Several studies have demonstrated that in clinically node-positive patients the FNR for SLNB after NST is influenced by molecular subtype. For patients with hormone receptor (HR)-positive (HR+) human epidermal growth factor receptor 2 (HER2)-positive (HER2+) or HR+HER2-negative (HER2–) breast cancer, FNRs of 24 or 29 percent, respectively, were reported, whereas the FNR was considerably lower when HR negative (HR–) HER2+ (7 percent) or triple-negative breast cancer (TNBC; 11 percent) subtype were predominant [17]. For TAD, this association has not been investigated in detail thus far. A subgroup analysis of the SenTa study indicated that the FNR for TAD was also higher in HR+ patients (2 of 37; 5.4 percent) than in those patients with HER2+ subtype (0 of 4; 0 percent) or TNBC (0 of 5; 0 percent) [20].

●Another controversy is how many lymph nodes (including or excluding the TLN) need to be evaluated for the TAD to be considered valid and axillary lymph node dissection avoided when all examined nodes are negative. The latest NCCN guidelines suggest that three sentinel lymph nodes (SLNs) plus the targeted lymph node (TLN) be removed. Some UpToDate authors believe that removing either two SLNs or the marked TLN is sufficient (algorithm 1). (See "General principles of neoadjuvant management of breast cancer", section on 'Assessment for pathologic complete response'.)

TECHNIQUES OF TARGETED AXILLARY DISSECTION — TAD has two components, sentinel lymph node biopsy (SLNB) and removal of targeted lymph node(s) (TLNs). The latter requires marking and localization of the TLN(s), which is described in detail below. SLNB is performed per standard techniques discussed elsewhere. (See "Sentinel lymph node biopsy in breast cancer: Techniques".)

Marking and localization of targeted lymph nodes — Patients with suspicious lesions in the breast and axilla routinely undergo a physical examination by palpation, followed by further investigation with imaging methods (eg, ultrasound and/or mammography) to aid in the detection of nonpalpable clinically node-positive disease, a prerequisite for TAD. (See "Overview of management of the regional lymph nodes in breast cancer", section on 'Axillary evaluation'.).

When suspicious lymph nodes are discovered, an ultrasound-guided core needle biopsy or fine needle aspiration of the TLNs is performed. The TLNs are marked either directly following the biopsy or after histopathologic confirmation of malignancy in the biopsied tissue.

Marking of the TLN(s) is particularly important for its later localization during or after neoadjuvant systemic therapy (NST), especially in patients with pathologic complete response in the initially metastatic lymph nodes, which might no longer be identifiable by imaging techniques. (See "General principles of neoadjuvant management of breast cancer", section on 'Assessment for pathologic complete response'.)

Numerous markers (figure 1) are commercially available [30,64]. The ideal marker has not been identified yet [26,60]. The IMTAD study intends to identify the ideal method (NCT04580251) to mark the TLN. Localization of the marked TLN can be, depending on the localization technique, performed pre-NST, during NST, or preoperatively after the end of NST, and helps to identify the TLN during surgery (figure 1).

Clips — The most common nonradioactive markers are metal clips, which are usually low-cost medical devices. Newer generation markers are ultrasound visible and 3 to 10 mm in size [65]. Some markers (eg, Tumark Vision) unfold to a spherical, three-dimensional structure immediately after deployment, thereby safely anchoring the marker in the appropriate location [66]. Other markers have a hygroscopic component (eg, HydroMARK) and substantially enlarge to their full size after being hydrated [67]. Clips might be subject to migration [64] and reduced visibility over time [68]. In routine clinical use, preoperative ultrasound visibility of the clipped TLN was achieved in 81 percent of patients, the intraoperative identification rate (IR) is low at 45 percent in those patients in whom the TLN could not be visualized preoperatively [20].

Commercially available nonradioactive marker clips are sold in combination with an applicator containing a needle (approximately 17 gauge) loaded with the clip [64,65]. The needle is usually ultrasound visible.

Localization of a clipped TLN is usually performed under ultrasound guidance and requires visualization of the TLN [20,69] (image 1). Alternatively, mammographic guidance is applied [20,35]. Traditionally, wire localization of the TLN has been applied [70]. Wire-guided localization has to take place either the day before surgery or directly preoperatively [20], thereby tightly linking the workflow of the radiologist and surgeon. One end of the thin metal wire is anchored into the TLN while the remaining segment of the wire is protruding from the patient [71]. However, as this procedure is associated with several drawbacks such as migration of the wire and discomfort to the patient, nonwire alternatives have been evaluated [61].

A clip costs approximately USD $25 to $120 [68], and if combined with wire-guided localization (USD $25 to $30), presents one of the low-cost TAD techniques [30,64].

Nonwire and nonradioactive devices — Nonwire and nonradioactive localization devices are commercially available as preloaded, ultrasound-visible needles. The respective localization marker can be deployed into the TLN by pressing a release mechanism [30,64].

●The nonradioactive radiofrequency identification device LOCalizer (12 mm in size) can be inserted into the TLN within a 30-day period prior to surgery [61,64].

●The Magseed is a magnetic seed of 5 mm in size, and as there is no limitation to the implantation period [64], long-term marking is feasible [36]. Magnetic localization amounts to USD $500 for one magnetic seed (Magseed) and approximately USD $55,000 for both the Sentimag probe and console.

●The SAVI SCOUT reflector (4 mm in size) can be applied for pre-NST localization as well [72]. This makes it easier to identify the untreated metastatic TLN and place the localization device within rather than outside the TLN [73]. The SAVI SCOUT reflector (USD $400) also requires the device-specific related probe and console (USD $40,000) [30,64].

●In one study, the TLN was located by intraoperative ultrasound [42].

Radioactive iodine seeds — A radioactive iodine-125 seed can be placed a few days prior to surgery into the clipped TLN via an 18-gauge needle [22], its position confirmed on ultrasound or mammography [74], and the radioactive seed can then be intraoperatively detected with a gamma counter [41,75]. This procedure is termed marking axillary lymph nodes with radioactive iodine seeds (MARI). However, the use of radioactive iodine seeds for this indication is only allowed in selected countries.

Radioactive iodine seeds cost USD $17 to $60. In case a probe (USD $15,000) and console (USD $30,000) are not already available, then those costs add up as well.

Carbon suspension — Several highly purified carbon suspensions (eg, CARBO‑REP) are commercially available and can be used for tattooing TLNs [76,77]. Approximately 0.2 to 0.8 mL of carbon dye [62,78] is injected into the nodal cortex of the TLN with a 20- to 25-gauge needle. As carbon particles are hyperechoic, their location in the TLN can be monitored by ultrasound as well [43]. A vial containing 5 mL carbon suspension is available at the price of approximately USD $100. When the TLN was initially marked with carbon suspension, intraoperative identification of the TLN solely relies on visual detection of black-dyed lymph nodes [62,78].

Tattooing of the TLN with a carbon suspension as a nonradioactive alternative has presented with good IRs, but in some cases ink migration into non-TLNs was observed [21,62]. Of note, tattooing axillary lymph nodes in breast cancer patients is considered off-label use in Europe [76].

Sentinel lymph node biopsy — SLNB as part of the TAD procedure should be performed according to local settings and respective clinical guidelines. (See "Sentinel lymph node biopsy in breast cancer: Techniques".).

Intraoperative identification of targeted lymph nodes — After transcutaneous localization of the TLN with the respective probe (figure 1) or guide wire, axillary incision is initiated [79]. Excision of the TLN is usually confirmed by specimen radiography (image 2) [20,31,80]. Thereafter, sentinel lymph nodes (SLNs) are removed. The TLN was identical to the SLN in >60 percent of TAD procedures [20,21,80].

Interpretation of pathology — In case TAD lymph nodes are metastasis-free on postoperative histopathologic evaluation (ypN0), then no further surgical action in the axilla is required. The identification of residual disease in TAD lymph nodes would indicate axillary lymph node dissection (ALND) in either the same or a second surgical session, although the recommendations are not clear when only isolated tumor cells are found [29]. Another controversy is how many lymph nodes (including or excluding the TLN) need to be evaluated for the TAD to be considered valid and ALND avoided when all examined nodes are negative. (See 'Controversial issues' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Breast surgery".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Sentinel lymph node biopsy for breast cancer (The Basics)")

●Beyond the basics topics (see "Patient education: Breast cancer guide to diagnosis and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Surgical options – In breast cancer patients with clinically positive lymph nodes (cN+) who have a complete pathologic response (ypN0) to neoadjuvant systemic therapy (NST), axillary lymph node dissection (ALND) may not be necessary; less invasive surgical options being investigated include:

•Sentinel lymph node biopsy (SLNB) alone,

•Targeted lymph node biopsy (TLNB) alone,

•Targeted axillary dissection (TAD; ie, SLNB plus TLNB).

Other options, including omitting axillary surgery, have also been proposed. (See 'Surgical options' above.)

●Clinical guidelines – There is no international consensus for surgical axillary staging of cN+ patients undergoing NST. Most clinical guidelines suggest TAD for patients with one to three suspicious lymph nodes at first presentation (cN1) and both ycN0 and ypN0, and ALND for more extensive nodal involvement (cN2-3) or any positive node found by TAD (ypN+). (See 'Clinical guidelines' above.)

●Technical performance – The technical performances of SLNB, TLNB, and TAD are listed below; however, they can vary by the marking and localization techniques, as well as individual studies (see 'Technical performance' above):

•Identification rate (IR):

-SLNB – 90 percent

-TLNB – 90 to 93 percent

-TAD – 87 to 98 percent

•False negative rate (FNR):

-SLNB – 19 percent (11 percent with dual tracers)

-TLNB – 4 to 7 percent

-TAD – 5 to 6 percent

●Clinical outcomes – The oncologic safety of TAD alone has been demonstrated in limited, nonrandomized studies. While awaiting higher-level clinical evidence, TAD seems to be a promising surgical approach that could spare patients the morbidity of ALND. However, a standard of care for axillary staging after neoadjuvant chemotherapy remains to be defined as alternative and newer techniques are still being evaluated and developed. (See 'Clinical outcomes' above.)

●Techniques – TAD requires a combination of the initial marking of the target lymph node and later localization (figure 1). Traditional approaches such as clip marking and post-NST wire localization are cost effective but are associated with a learning curve. Alternative techniques using radioactive or nonradioactive devices allow pre-NST localization and enable excellent intraoperative identification; however, they are associated with higher costs. (See 'Techniques of targeted axillary dissection' above.)