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Overview of management of the regional lymph nodes in breast cancer

Overview of management of the regional lymph nodes in breast cancer
Authors:
Seth P Harlow, MD
Donald L Weaver, MD
Section Editors:
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Daniel F Hayes, MD
David E Wazer, MD
Deputy Editors:
Wenliang Chen, MD, PhD
Sadhna R Vora, MD
Literature review current through: Jan 2024.
This topic last updated: Aug 31, 2022.

INTRODUCTION — The lymphatic drainage areas of the breast (axillary, internal mammary, and supraclavicular nodal groups) are the nodes most likely to be involved in patients with metastatic breast cancer.

The risk of breast cancer spreading to regional lymph nodes, the preoperative assessment of the axilla, and the indications for axillary dissection and axillary radiation are reviewed in this topic.

The techniques for performing a sentinel lymph node biopsy (SLNB), an axillary lymph node dissection (ALND), axillary radiation, and the management of the axilla in the clinical setting of neoadjuvant therapy are discussed elsewhere.

●(See "Overview of sentinel lymph node biopsy in breast cancer".)

●(See "Sentinel lymph node biopsy in breast cancer: Techniques".)

●(See "Technique of axillary lymph node dissection".)

●(See "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla'.)

●(See "Radiation therapy techniques for newly diagnosed, non-metastatic breast cancer", section on 'Regional node RT'.)

REGIONAL LYMPH NODES RELEVANT TO BREAST CANCER — The axillary lymph nodes receive the majority of the lymphatic drainage from all quadrants of the breast; the remainder drains to the internal mammary, infraclavicular, and/or supraclavicular lymph nodes.

Axillary lymph nodes — The axillary lymph nodes (ALNs) receive 85 percent of the lymphatic drainage from all quadrants of the breast.

The likelihood of ALN involvement is related to tumor size, location, and certain histologic features (eg, grade, lymphatic invasion, receptor status) [1,2].

●Tumor size – In general, larger primary tumors are associated with a higher likelihood of ALN involvement (although this can vary with tumor subtype) [3-5]. As an example, in a series of 6800 women diagnosed with invasive breast cancer after screening mammography, the incidence rate of ALN involvement increased with tumor size (table 1) [6].

However, ALN metastases are relatively common even with invasive breast cancers ≤1 cm in size [1,2,7-10]. In a report of 919 women who underwent ALN dissection, ALN metastases were detected in 16 and 19 percent of those with T1a (tumor size 0.1 to 0.5 cm in greatest dimension) and T1b tumors (tumor size 0.5 to 1.0 cm), respectively [10]. (See "Tumor, node, metastasis (TNM) staging classification for breast cancer".)

●Tumor location – ALNs are more commonly involved with tumors in the lateral rather than the medial portion of the breast [3,11,12]. As an example, in a study of 1671 early-stage breast cancers, the odds ratio of a lateral tumor having ALN metastasis was 1.33 (95% CI 0.95-1.87) relative to a medial tumor [13]. The most likely explanation for this difference is the preferential drainage of some medial tumors to the internal mammary nodes [14]. (See 'Internal mammary lymph nodes' below.)

●Histologic features – Grade 1 tumors have a significantly lower rate of ALN metastases compared with grade 2 or 3 tumors [9]. As an example, in data derived from the Surveillance, Epidemiology, and End Results (SEER) database, the incidence of ALN involvement in patients with grade 1 and grade 3 tumors of similar size was 3.4 and 21 percent, respectively [9].

Tumors that are associated with a less than 5 percent risk of ALN metastases include those with a single focus of microinvasion [15,16], <5 mm grade 1 tumors without lymphatic invasion, and pure mucinous or pure tubular carcinomas <1 cm [17,18]. (See "Pathology of breast cancer".)

Correcting for size, some tumor subtypes (eg, HER2+, triple-negative) have higher node positivity rates than others (eg, luminal).

●Detection method of primary tumor – Across all size categories, patients whose invasive tumors are detected by screening mammography are more likely to have pathologically negative lymph nodes than those with clinically detected tumors [6].

●Management – The preoperative evaluation and management of metastatic axillary lymph nodes in breast cancer is discussed in detail below. (See 'Axillary evaluation' below and 'Axillary management' below.)

Internal mammary lymph nodes

●Presentation – Like the ALNs, the internal mammary nodes (IMNs) receive lymph drainage from all quadrants of the breast [19]. However, medial tumors have a significantly higher rate of IMN metastases [20]. Although the IMN chain extends from the fifth intercostal space to the retroclavicular region, nodes in the upper three interspaces are most likely to contain metastases [21-23].

Isolated IMN metastases are infrequent; more often, ALNs are involved as well [14,20,24]. In a report of over 7000 cases in which the IMNs and ALNs were examined, IMN metastases were detected in 22 percent, but fewer than 5 percent of the node-positive patients had IMN-only disease [14]. Isolated IMN involvement was more frequent for medial than lateral tumors (7.6 versus 2.9 percent).

●Imaging – There are no convincing data that routine imaging of IMNs is needed in clinically node-negative breast cancer patients. They may be imaged as part of staging positron emission tomography (PET) or chest computed tomography (CT) scans, which patients undergo if there is concern for metastatic disease. The results may change the patient's nodal stage and impact surgical and radiation treatments. (See "Clinical features, diagnosis, and staging of newly diagnosed breast cancer", section on 'Role of imaging'.)

●Management – The management of IMNs is controversial.

•Sentinel lymph node biopsy – Dissection of the IMNs with SLNB is considered investigational [20,25-29]. Using standard technique, IMNs are only visualized in 20 percent of patients during SLNB. An IMN is rarely positive if an axillary sentinel lymph node is removed that is negative. Given that the IMN status rarely changes management, and that the nodes in the axilla usually reflect the IMN status, very few surgeons would perform SLNB of an IMN or even try to identify them preoperatively with lymphoscintigraphy. Potential complications of IMN SLNB include pleural effusion and injury to the internal mammary artery [30]. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'Internal mammary nodes'.)

•Radical dissection – Following four early (1960s) randomized trials showing no survival benefit from extended mastectomy (which included IMN dissection) compared with radical or modified radical mastectomy (even in the absence of chemotherapy), routine dissection of IMN was abandoned [31-34]. Furthermore, the widespread use of adjuvant systemic therapy for women with both node-positive and node-negative breast cancer has diminished the importance of the IMNs in clinical care.

•Radiation therapy – However, for women receiving adjuvant regional radiation therapy (RT), either after breast-conserving surgery or with postmastectomy RT (PMRT), RT of the IMNs is generally included. Indications for regional RT are discussed elsewhere. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Indications for regional nodal irradiation' and "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Patients treated with mastectomy'.)

However, an individualized approach is necessary that takes into account the patient's risk for IMN involvement, the anatomy, and the ability to exclude critical structures (eg, the heart) from the treatment field. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'RT of internal mammary nodes'.)

Supraclavicular lymph nodes

●Presentation – Supraclavicular nodal metastases are usually associated with extensive ALN involvement and are rare in its absence. As an example, in a series of 274 women undergoing routine supraclavicular dissection, supraclavicular nodal metastases were found in 18 and 0.7 percent of those with and without ALN metastases, respectively [35].

●Management – Supraclavicular nodal metastases represent locally advanced disease. Nonetheless, curative treatment is possible with aggressive multimodality treatment, typically consisting of neoadjuvant systemic therapy, surgery, possible adjuvant systemic therapy, and radiation [36,37].

AXILLARY EVALUATION — The axilla of patients with breast cancer can be assessed with physical examination, axillary ultrasound, and/or percutaneous needle biopsy (core needle biopsy [CNB] or fine needle aspiration [FNA]). The optimal pathway depends on the tumor size and pathologic features, including its receptor status, as these factors influence whether neoadjuvant systemic treatment will be offered.

Physical examination — All patients undergo physical examination of the axilla. However, it is neither sensitive nor reliable in ascertaining the status of the axillary lymph nodes (ALNs) because metastatic lymph nodes are often not palpable, and reactive lymph nodes may be mistaken for metastases. The positive predictive value of clinical palpation (ie, likelihood of finding axillary metastases in a patient with suspicious findings on physical examination) ranges from 61 to 84 percent, while the negative predictive value (ie, the likelihood that axillary nodal metastases are absent in a patient with no suspicious findings on physical examination) is only 50 to 60 percent [38-40]. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 sentinel node trial, in patients with negative axillary nodes by clinical examination, the node-positive rate was 26 percent [41]. However, the risk of individual patients is influenced by factors such as tumor size (table 1). (See "Clinical manifestations, differential diagnosis, and clinical evaluation of a palpable breast mass", section on 'Palpation'.)

Axillary ultrasound — Axillary ultrasound is an effective screening method for detecting nodal metastasis in patients with invasive breast cancer (image 1 and image 2) [42]. However, the efficacy of ultrasound-guided biopsy can vary between centers because the accuracy of ultrasound examination is operator dependent [43]. (See "Diagnostic evaluation of suspected breast cancer", section on 'Axillary ultrasound'.)

The use of axillary ultrasound in patients with newly diagnosed invasive breast cancer varies between centers [44]. Some experts routinely perform axillary ultrasound in all patients with a newly diagnosed invasive breast cancer, while others only perform ultrasound for clinically positive (palpable) nodes or when neoadjuvant chemotherapy is planned.

For patients who are not planning to undergo neoadjuvant chemotherapy, the benefit of preoperative axillary ultrasound is debated:

●Proponents argue that ultrasound staging can identify patients with a high axillary disease burden (≥3 metastatic nodes, extranodal extension, or level III nodes), who may go straight to ALND [45-47]. In a retrospective study of patients who had only one metastatic node on preoperative ultrasound and who met the Z0011 criteria, preoperative ultrasound had a sensitivity and negative predictive value of 92 percent and false negative rate of 8 percent; the performance of ultrasound was comparable to that of SLNB [48].

●Opponents argue that early breast cancer patients are not likely to have a large number of involved axillary nodes. They further argue that ultrasound cannot differentiate between one or two positive nodes from three or more positive nodes and thus does not have sufficient negative predictive value to bypass sentinel lymph node biopsy (SLNB) and does not add more information to SLNB [49-52].

Three ongoing trials, Sentinel Node Versus Observation After Axillary Ultrasound (SOUND, NCT02167490), Intergroup-Sentinel-Mamma (INSEMA) [53], and Clinically Node Negative Breast Cancer Patients Undergoing Breast Conserving Therapy: Sentinel Lymph Node Procedure Versus Follow-Up (BOOG 2013-08) [54], are evaluating whether patients with negative axillary ultrasound require additional axillary surgery. The results may clarify the requirement for axillary ultrasound staging in breast cancer and may further deescalate axillary surgical management for breast cancer when axillary ultrasound is negative.

For patients who are planning to undergo neoadjuvant chemotherapy, the benefit of preoperative axillary ultrasound is that it permits targeted axillary dissection by identifying, guiding biopsy of, and marking any positive node(s) [47] (see 'Comparison of treatment modalities' below). In the Z1071 trial, targeted axillary dissection reduced the false negative rate of SLNB from 12.6 to 6.8 percent in patients with positive axillary nodes undergoing neoadjuvant treatment [55].

Percutaneous needle biopsy — Abnormal lymph nodes identified on axillary ultrasound should undergo needle biopsy for pathologic analysis [42,44,56-61]. Such biopsies, either CNB or FNA, can be performed percutaneously under ultrasound guidance. However, until further data become available, needle biopsy of an abnormal axillary lymph node(s) does not obviate surgical evaluation of the axilla, and SLNB is still required in most patients with breast cancer. (See "Breast biopsy".)

AXILLARY MANAGEMENT — The decision to give neoadjuvant chemotherapy, endocrine therapy, and immunotherapy depends on the hormone receptor and HER2 status and stage of the cancer. The selection of patients for neoadjuvant therapy is discussed elsewhere. (See "General principles of neoadjuvant management of breast cancer", section on 'Patient selection'.)

Our approach to axillary management depends, in part, on whether a patient received neoadjuvant treatment. (See 'Patients who do not undergo neoadjuvant therapy' below and 'Patients who undergo neoadjuvant therapy' below.)

Benefit of axillary treatment — Axillary treatment improves regional disease control; however, with improved systemic treatment, there is no clear evidence of an improvement in overall survival.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial, clinically node-negative patients were randomly assigned to total mastectomy and axillary lymph node dissection (ALND), total mastectomy with regional radiation therapy (RT), or total mastectomy only with delayed ALND at the time of recurrence [62]. Although the 10 year survival was similar in the three groups, the axillary failure rate was significantly higher in women treated with mastectomy alone (without ALND or regional RT; 18 percent) compared with those undergoing regional RT or initial ALND (3.1 and 1.4 percent, respectively). The rate of axillary failure was probably higher than 18 percent in those undergoing delayed ALND because inoperable axillary recurrences and operable axillary recurrences that occurred simultaneously with or after distant metastases were excluded. It should be noted, however, that the time period for this study was 1971 to 1974, when the use of mammographic screening was neither widespread nor as sophisticated as it is presently, and adjuvant systemic therapy was less refined. Additionally, the mean tumor size in this study was generally larger than currently identified.

Since the likelihood of subclinical axillary metastases increases with increasing tumor size, we would anticipate that axillary failure rates without dissection or radiation today would be significantly lower than 18 percent, especially in light of contemporary adjuvant systemic treatment regimens. Indeed, the axillary relapse rate in the Z0011 trial was 0.5 percent with ALND and 1 percent with SLNB alone [63].

Comparison of treatment modalities — There are two modalities of axillary treatment for breast cancer, surgery (sentinel lymph node biopsy [SLNB], targeted axillary dissection [TAD], or ALND) and radiation (regional radiotherapy). Given randomized trial data showing that many women with limited or no sentinel lymph node involvement can safely omit ALND and be treated with radiation only, this has become the standard approach for women who meet "Z0011" criteria, as discussed elsewhere. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'Management after sentinel lymph node biopsy'.)

●Sentinel lymph node biopsy – In patients with clinically node-negative early breast cancer, SLNB identifies patients with limited or no axillary lymph node (ALN) involvement who may therefore be able to avoid more extensive surgery. The decision about proceeding with ALND is based on the results of SLNB, primary tumor size, and other factors. (See "Overview of sentinel lymph node biopsy in breast cancer".)

Both surgical and radiation therapies to the axilla increase the risk of long-term ipsilateral arm lymphedema, and so use of both together is often avoided, except in very-high-risk circumstances. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Involved lymph nodes'.)

●Targeted axillary dissection – TAD is an axillary staging technique that removes any biopsy-proven positive axillary nodes, which are marked with a clip or tattoo prior to neoadjuvant chemotherapy, in addition to SLNB. TAD is an adaptation of axillary sampling that targets removal of positive nodes while minimizing morbidity. In a meta-analysis of over 3000 patients, the pooled success rate of identifying and retrieving a marked node was 90.0 percent (95% CI 85.1-95.1). Compared with ALND in 13 studies, TAD was associated with a false negative rate of 5.18 percent (95% CI 3.41-7.54) [64].

●Axillary lymph node dissection – Histologic examination of removed lymph nodes from an ALND is the most accurate historical method for assessing local spread of disease to regional nodes. The potential utility of ALND for patients with clinically positive axillary nodes includes its impact on disease control (ie, axillary recurrence), its prognostic value, and its role in treatment selection. However, the anatomic disruption caused by ALND may result in lymphedema, nerve injury, and shoulder dysfunction, which compromise functionality and quality of life. As such, although ALND was once a routine component of the staging and management of breast cancer [65], SLNB is now accepted as the standard initial approach for women with early breast cancer who meet the Z-0011 criteria [66]. (See "Technique of axillary lymph node dissection".)

●Regional radiotherapy – Standard whole breast radiation therapy (WBRT), offered to women after breast-conserving surgery or postmastectomy radiation therapy (PMRT), includes two tangential radiation fields to the breast or chest wall, which generally covers the low ipsilateral axillary nodes. Full regional RT is defined as the use of an additional third radiation field and in some cases a fourth field to ensure treatment of the supraclavicular, infraclavicular, and upper ALNs. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

Several randomized trials have directly compared locoregional failure rates and survival in women treated with ALND or regional RT in women with early-stage breast cancer [67-69]. All have shown low rates of axillary failure after either ALND or regional RT and similar long-term survival, and as such, many women are able to avoid ALND, with incorporation of regional RT. The selection of women who may be able to avoid ALND is according to the results of SLNB. (See 'Patients who do not undergo neoadjuvant therapy' below and 'Patients who undergo neoadjuvant therapy' below.)

Two trials comparing ALND and RT are as follows:

●Reported in 2014, the After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trial was a multi-institutional trial [70]. The trial included 4806 patients with T1 or T2 primary, unifocal, invasive breast cancer without palpable axillary lymphadenopathy. Of the 1425 patients who were found to have positive sentinel lymph nodes by SLNB, 744 were randomly assigned to receive ALND and 681 to receive axillary radiotherapy. Ninety-five percent of patients in both groups had one or two positive sentinel nodes. The five-year axillary recurrence rate was 0.43 percent (95% CI 0-0.92) in the ALND group and 1.19 percent (95% CI 0.31-2.08) in the axillary radiation group. There were no statistically significant differences in survival between treatment groups. Lymphedema was noted significantly more often after ALND than after axillary radiation at one, three, and five years.

The 10 year follow-up results of the AMAROS trial have been reported in abstract form [71]. After 10 years, the axillary recurrence rate remained low and comparable between the ALND group (7/744 patients; 0.93 percent) and the axillary radiotherapy group (11/681 patients; 1.82 percent). Distant metastasis-free survival and overall survival rates were similar. While this trial did find more second primary cancers developed in patients treated with axillary radiotherapy (11.0 versus 7.7 percent, p = 0.035), some of these cancers were contralateral breast cancers. It is unclear how much of this was due to the axillary radiation versus chance alone.

●In the OTOASOR trial, 474 patients with cT ≤3 cm, cN0, and pN1 (sentinel node) breast cancer were randomly assigned to completion ALND versus axillary RT. There was no statistically significant difference in axillary recurrence or overall survival between the two groups of patients at 40 months (axillary recurrence 0.82 percent ALND, 1.3 percent RT) [72] and at 97 months (axillary recurrence 2 percent ALND, 1.7 percent RT; overall survival 77.9 versus 84.8 percent; disease-free survival 72.1 versus 77.4 percent) [73].

Patients who do not undergo neoadjuvant therapy — Most patients without known axillary metastases undergo SLNB, with choices regarding ALND or regional nodal irradiation (or both) depending on the results of the SLNB. (See 'No known axillary nodal metastasis' below.)

The approach to patients with known axillary metastases is described below. (See 'Known axillary nodal metastasis prior to surgery' below.)

No known axillary nodal metastasis — Preoperative axillary evaluation is discussed above. (See 'Axillary evaluation' above.)

Patients who have no axillary nodal metastasis found on preoperative axillary evaluation should proceed directly to SLNB at the time of primary breast surgery. For such patients, SLNB is the standard method for axillary staging and can reliably distinguish between patients requiring ALND and those for whom radiation alone or observation is sufficient [44,74-76].

Further management of the axilla depends on the outcomes of the SLNB (algorithm 1):

No positive sentinel node — Patients who do not have nodal metastases on SLNB do not require ALND. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'No sentinel node metastasis'.)

Randomized trials including patients with high-risk node-negative disease have suggested improvements in breast-cancer-free survival with regional RT [77,78]; as such, we offer regional RT in addition to WBRT to women with high-risk, node-negative disease, although this practice varies between centers. High-risk disease includes T3 or T4 disease as well as those with T2 tumors who have undergone limited axillary dissection (<10 lymph nodes) and also have other risk factors, including high-grade histology, estrogen receptor (ER)-negative tumors, or lymphovascular invasion [78]. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'High-risk features of the primary tumor'.)

For the majority of patients who do not have high-risk features of the primary tumor, regional RT is not required.

One or two positive sentinel nodes

●Breast-conserving surgery – For most patients who have one or two sentinel lymph node metastases and will receive breast-conserving surgery with WBRT, we do not perform completion ALND.

For many of these patients, we offer the addition of regional RT to WBRT. However, this practice also varies between centers; some centers use only WBRT, as this was the strategy performed in the Z-0011 trial; other centers raise the breast tangents to radiate more of the axilla without adding additional fields. Available data are discussed in detail elsewhere. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Involved lymph nodes'.)

An exception is that for women with micrometastatic disease to one to two lymph nodes, in general, we do not add regional RT in the absence of other high-risk features. However, regional RT may be added in patients with micrometastatic lymph node disease if other high-risk features are present. Again, this is not a uniform practice across all centers. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Exception for micrometastatic nodal disease'.)

●Mastectomy – For patients who have one or two sentinel lymph node metastases, we do not perform complete ALND. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'One or two sentinel node metastases' and "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

We offer postmastectomy radiation therapy (PMRT) for such patients. Although there is some debate, we generally proceed with PMRT for these patients to maximize the opportunity to reduce the risk of recurrence and potentially improve disease-specific survival, based on data from randomized trials [79,80]. However, given that the absolute magnitude of benefit derived depends on the baseline risk of locoregional failure, an individualized approach that takes into account patient preference and high-risk features is necessary. Those with micrometastatic diseases only do not require PMRT unless there are high-risk features.

Patients who desire immediate reconstruction after mastectomy may not be optimal candidates for PMRT, because of cosmetic concerns. Some centers offer such patients PMRT with a tissue expander to circumvent contractions and other wound issues that can occur with radiation.

More positive lymph nodes — Our practice with regard to number of positive sentinel nodes is as follows: we perform completion ALND in patients with three or more positive sentinel nodes, regardless of whether they had mastectomy or breast-conserving surgery. The need for regional RT would be discussed with regard to risk factors. For patients with four or more nodes, we typically administer comprehensive regional RT; patients with one to three nodes with other high-risk features (large primary tumor, extensive lymphovascular invasion, etc) typically also receive regional RT. Regional RT is more controversial for those with small tumors (T1 or T2) with one to three nodes without extracapsular disease or extensive lymphovascular invasion and is discussed in more detail elsewhere, both for those who undergo breast-conserving therapy (see "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Involved lymph nodes') as well as for those who undergo mastectomy. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Involved lymph nodes'.)

Regional RT, when performed after breast-conserving therapy, is performed in addition to WBRT and as a part of PMRT (in addition to chest wall radiation) after mastectomy. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'Three or more sentinel node metastases'.)

Known axillary nodal metastasis prior to surgery — Patients with clinically bulky, biopsy-confirmed node-positive disease (eg, via needle biopsy) prior to breast surgery who do not undergo neoadjuvant treatment are managed with ALND at the time of the primary breast procedure, given high recurrence rates in this high-risk population [81]. Such patients are also often recommended for adjuvant regional RT.

Patients with node-positive disease based on biopsy alone (ie, non-clinically bulky) can undergo SLNB, with further management dictated by the result of SLNB. (See 'Patients who do not undergo neoadjuvant therapy' above.)

The use of RT in such patients is discussed elsewhere. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Involved lymph nodes'.)

Omitting axillary surgery

Select older patients with small hormone receptor-positive tumors — Select older patients with small (≤3 cm) ER-positive, HER-2/neu-negative tumors who will receive adjuvant endocrine therapy and who are clinically node negative may be managed without any axillary surgery [82-84]. That is because knowledge of the status of the axillary lymph nodes may not influence treatment recommendations or outcomes in these patients [85]. The exact criteria for omitting axillary surgery may vary by guidelines [86]. Additionally, chronologic age may differ from "biological age," and some older women with good baseline health may have a higher likelihood of benefit from treatments such as RT or chemotherapy than a younger patient with significant comorbidities. Other risk factors (eg, tumor grade, intensity of ER expression, etc) also need to be considered. (See "Overview of the approach to early breast cancer in older women", section on 'Management of the axilla'.)

Most cases of ductal carcinoma in situ — By definition, in situ cancer does not metastasize. However, lymph node metastases are found in 0.2 and 0.7 percent of ductal carcinoma in situ (DCIS) due to the occasional undetected presence of an invasive cancer component in the surgical specimen [87,88]. Hence, axillary staging in the form of SLNB is only required for patients undergoing mastectomy. Some opt to do SLNB in cases of DCIS with suspicious features suggestive of underlying invasive cancer; however, for patients undergoing lumpectomy, an SLNB can always be done after the upstaged diagnosis to invasive disease is found. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'DCIS with planned mastectomy or suspicious features'.)

Patients who undergo neoadjuvant therapy — For patients undergoing neoadjuvant therapy, after its completion, the axilla should be reevaluated with clinical examination and possibly a repeat ultrasound according to some authors. The information gathered by the axillary assessments prior to and after neoadjuvant therapy should inform the choice of axillary surgery (SLNB versus ALND). Unless there is clear evidence of residual nodal disease, most experts would favor an SLNB given the higher morbidity of ALND; nodes that appear suspicious radiographically may be negative on pathology evaluation. (See "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla'.)

Although it is our practice to perform SLNB after neoadjuvant chemotherapy (NACT), some institutions perform SLNB prior to NACT. The decision regarding when to perform SLNB in patients receiving NACT is discussed elsewhere. (See "General principles of neoadjuvant management of breast cancer", section on 'Those with SLNB prior to treatment'.)

The management of the axilla in patients receiving neoadjuvant therapy is briefly outlined below. It is discussed in much more detail in this algorithm (algorithm 2) and in another topic. (See "General principles of neoadjuvant management of breast cancer".)

Initial cN0 to cN1 disease and clinically node negative after neoadjuvant therapy — Patients who are initially clinically node negative, or patients with cN1 (metastasis to movable ipsilateral level I, II axillary lymph nodes) disease who become node negative after neoadjuvant therapy, are eligible for SLNB. This should, when possible, be combined with removal of any node that was positive by biopsy prior to neoadjuvant treatment and marked by a clip (referred to by some as targeted axillary dissection) (see 'Comparison of treatment modalities' above). Further axillary treatment depends on the result of surgical axillary staging, as discussed in the sections below. (See 'Sentinel node identified and pathologically negative' below and 'Positive sentinel node(s)' below.)

There is no consensus on axillary management after neoadjuvant therapy in patients with clinically node-positive (cN+) breast cancer. In a 2022 survey by the European Breast Cancer Research Association of Surgical Trialists, the most common post-neoadjuvant therapy axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (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 targeted lymph node biopsy (2.5 percent) [89].

Sentinel node identified and pathologically negative — These patients (ypN0) do not require completion ALND. (See "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla'.)

The decision regarding whether axillary radiation is delivered depends on the initial stage, the response to therapy, and other high-risk features (see "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Patients who received neoadjuvant therapy'):

●Patients presenting with initial stage I disease (cN0) with a complete pathologic response in the breast and axilla are not treated with ALND or regional RT.

●Patients who initially presented with stage II disease who have a complete response to treatment need individualized decision making with regard to adjuvant regional RT, taking into account pretreatment risk factors. We would typically not administer radiation unless the patient had clinical N1 disease at presentation.

●For those who initially presented with stage III disease or those with any initial-stage disease who have residual breast disease, we offer regional RT, either in addition to WBRT after breast-conserving surgery or as a part of PMRT after mastectomy. However, we recognize that this approach is controversial, and our threshold to omit regional radiation in such patients is lower than for patients with residual nodal disease. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Patients who received neoadjuvant therapy'.)

Positive sentinel node(s) — For patients with any positive sentinel node after neoadjuvant therapy (ypN+), we offer maximal axillary therapy consisting of completion ALND followed by regional RT. For now, ALND remains standard care in patients with residual disease after neoadjuvant chemotherapy while the results of Alliance A011202 (NCT01901094) are pending [90]. (See "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla' and "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Patients who received neoadjuvant therapy'.)

Initial cN2 or cN3 disease, or clinically node positive after neoadjuvant therapy — ALND followed by regional RT is also appropriate for patients with either initial cN2 or cN3 disease (metastasis in fixed/matted axillary nodes or internal mammary, infraclavicular, or supraclavicular nodes) or those with any stage disease found to have a persistently positive lymph node after neoadjuvant treatment. (See "General principles of neoadjuvant management of breast cancer", section on 'Positive axilla prior to treatment' and "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Patients who received neoadjuvant therapy'.)

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 5th to 6th 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 10th to 12th 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.)

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

SUMMARY AND RECOMMENDATIONS

●Axillary evaluation – Axillary physical examination is performed in all patients with breast cancer. Axillary ultrasound may be performed, although practice varies between centers. Percutaneous, ultrasound-guided needle biopsy should be performed for abnormal lymph nodes detected on ultrasound. (See 'Axillary evaluation' above.)

●Axillary management – The need for surgery, radiation, or both depends on the result of the axillary evaluation and whether the patient undergoes neoadjuvant therapy. (See 'Comparison of treatment modalities' above.)

●Patients who do not undergo neoadjuvant therapy – Patients who do not require neoadjuvant therapy generally undergo either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) with their primary breast procedure (algorithm 1). (See 'Patients who do not undergo neoadjuvant therapy' above and "Overview of sentinel lymph node biopsy in breast cancer", section on 'Management after sentinel lymph node biopsy'.)

•Patients with clinically node-negative axilla should undergo SLNB, the result of which directs further treatment (see "Overview of sentinel lymph node biopsy in breast cancer"):

-Pathologically negative sentinel nodes – Patients who do not have nodal metastases on SLNB do not require ALND, and the majority do not require regional radiation therapy (RT). We offer regional RT for select patients with high-risk features, although this practice varies between centers. (See 'No positive sentinel node' above.)

-One or two positive sentinel node(s) – For such patients, we do not perform completion ALND, but for those who undergo mastectomy, we administer postmastectomy RT (PMRT). We offer regional RT for those who undergo breast-conserving therapy in addition to whole breast RT (WBRT), although this practice varies between centers. (See 'One or two positive sentinel nodes' above.)

-More positive sentinel nodes – For patients with three or more positive lymph nodes, we proceed with both completion ALND and regional RT. (See 'More positive lymph nodes' above.)

We recognize, however, that regional RT is controversial in those with fewer than four involved lymph nodes. (See 'More positive lymph nodes' above.)

•For patients with clinically bulky and biopsy-proven node-positive disease who do not undergo neoadjuvant treatment, we suggest ALND at the time of the primary breast procedure rather than SLNB or nodal radiation alone (Grade 2C). Patients with a positive node based on ultrasound-guided biopsy alone may undergo SLNB. (See 'Patients who do not undergo neoadjuvant therapy' above.)

The use of regional RT in such patients is discussed elsewhere. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Involved lymph nodes'.)

•Select older patients with early-stage estrogen receptor (ER)-positive, HER-2/neu-negative tumors who are clinically node negative and who will receive adjuvant endocrine therapy may be managed without any axillary surgical assessment. (See 'Omitting axillary surgery' above.)

●Patients who undergo neoadjuvant therapy – After neoadjuvant therapy, the axilla should be reexamined clinically with or without another ultrasound (algorithm 2). (See 'Patients who undergo neoadjuvant therapy' above and "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla'.)

•Patients who are initially clinically node negative (cN0), or patients with cN1 disease who become pathologically node negative after neoadjuvant therapy, should undergo SLNB (with removal of any clipped node) at the time of surgery (after neoadjuvant chemotherapy), the result of which directs further treatment:

-Pathologically negative sentinel nodes – These patients (ypN0) do not require completion ALND. However, the decision regarding whether axillary radiation is delivered depends on the initial stage, the response to therapy, and other high-risk features. (See 'Sentinel node identified and pathologically negative' above.)

-Any positive sentinel node(s) – For patients with any number of positive sentinel nodes after neoadjuvant therapy (ypN+), we proceed with completion ALND followed by regional RT. (See 'Positive sentinel node(s)' above.)

•Patients with either initial cN2 or cN3 disease (regardless of response to neoadjuvant treatment), or a persistently positive lymph node after neoadjuvant treatment regardless of stage, should undergo ALND and regional RT. (See 'Initial cN2 or cN3 disease, or clinically node positive after neoadjuvant therapy' above.)

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Topic 813 Version 30.0

References

1 : Identification of women with T1-T2 breast cancer at low risk of positive axillary nodes.

2 : The value of axillary dissection in T1a breast cancer.

3 : Management and survival of female breast cancer: results of a national survey by the American College of Surgeons.

4 : Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases.

5 : Predicting axillary nodal positivity in 2282 patients with breast carcinoma.

6 : Pathologic findings from the Breast Cancer Surveillance Consortium: population-based outcomes in women undergoing biopsy after screening mammography.

7 : The impact of histopathology on nodal metastases in minimal breast cancer.

8 : Predictors of axillary lymph node metastases in patients with T1 breast carcinoma.

9 : Prediction of axillary lymph node status in breast cancer patients by use of prognostic indicators.

10 : Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients.

11 : Location of breast carcinoma and prognosis.

12 : Site of primary tumor has a prognostic role in operable breast cancer: the international breast cancer study group experience.

13 : Risk factors for axillary lymph node metastases in clinical stage T1-2N0M0 breast cancer patients.

14 : Staging of breast cancer: a new rationale for internal mammary node biopsy.

15 : The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer.

16 : Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation.

17 : Tubular carcinoma of the breast. Clinical and pathological observations concerning 135 cases.

18 : Tubular carcinoma of the breast. Clinical pathologic correlations based on 100 cases.

19 : Internal mammary lymph node drainage patterns in patients with breast cancer documented by breast lymphoscintigraphy.

20 : Internal mammary nodes in breast cancer: diagnosis and implications for patient management -- a systematic review.

21 : Incidence of metastasis in the internal mammary chain in operable cancer of the breast.

22 : Excision of the internal mammary chain in radical mastectomy; results in 57 cases.

23 : Significance of internal mammary lymph node metastases in breast cancer.

24 : Extra-Axillary Sentinel Lymph Nodes in Breast Cancer.

25 : Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique: High Visualization Rate and Accurate Staging.

26 : ASO Author Reflections: Internal Mammary Sentinel Lymph Node Biopsy-Time for the Back of Internal Mammary Staging?

27 : Sentinel lymph node mapping in breast cancer: a critical reappraisal of the internal mammary chain issue.

28 : A selection algorithm for internal mammary sentinel lymph node biopsy in breast cancer.

29 : Internal mammary sentinel lymph node mapping for invasive breast cancer: implications for staging and treatment.

30 : Internal mammary sentinel lymph node biopsy: abandon or persist?

31 : A controlled trial of extended radical versus radical mastectomy. Ten-year results.

32 : Radical mastectomy versus radical mastectomy plus internal mammary dissection. Ten year results of an international cooperative trial in breast cancer.

33 : Five-year results of a randomized clinical trial comparing modified radical mastectomy and extended radical mastectomy for stage II breast cancer.

34 : The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial.

35 : [Research on the microscopic metastases of breast cancers into the para-sternal and subclavicular lymph nodes].

36 : Treatment Patterns and Outcomes of Women with Breast Cancer and Supraclavicular Nodal Metastases.

37 : ASO Author Reflections: Impact of Ipsilateral Supraclavicular Lymph Node Dissection on Breast Cancer.

38 : Accuracy of ultrasound and clinical examination in the diagnosis of axillary lymph node metastases in breast cancer.

39 : Assessment of clinical palpation of the axilla as a criterion for performing the sentinel node procedure in breast cancer.

40 : Role of ultrasonography to detect axillary node involvement in operable breast cancer.

41 : Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial.

42 : Axillary ultrasound assessment in primary breast cancer: an audit of 653 cases.

43 : Meta-analysis of ultrasound-guided biopsy of suspicious axillary lymph nodes in the selection of patients with extensive axillary tumour burden in breast cancer.

44 : Management of the Axilla in Early-Stage Breast Cancer: Ontario Health (Cancer Care Ontario) and ASCO Guideline.

45 : Predicting the extent of nodal disease in early-stage breast cancer.

46 : The role of ultrasound-guided lymph node biopsy in axillary staging of invasive breast cancer in the post-ACOSOG Z0011 trial era.

47 : Lymph Node Staging in Newly Diagnosed Breast Cancer: Point-Preoperative Staging Axillary Ultrasound Is Valuable in the Contemporary Evaluation of Newly Diagnosed Breast Cancer.

48 : Preoperative Sonographic Prediction of Limited Axillary Disease in Patients with Primary Breast Cancer Meeting the Z0011 Criteria: an Alternative to Sentinel Node Biopsy?

49 : Is Preoperative Axillary Imaging Beneficial in Identifying Clinically Node-Negative Patients Requiring Axillary Lymph Node Dissection?

50 : Preoperative ultrasound-guided needle biopsy of axillary nodes in invasive breast cancer: meta-analysis of its accuracy and utility in staging the axilla.

51 : Does a Positive Axillary Lymph Node Needle Biopsy Result Predict the Need for an Axillary Lymph Node Dissection in Clinically Node-Negative Breast Cancer Patients in the ACOSOG Z0011 Era?

52 : Lymph Node Staging in Newly Diagnosed Breast Cancer: Counterpoint-Sentinel Biopsy Surpasses Axillary Imaging in Early-Stage Cancers, but Is the Sun Setting on This Controversy?

53 : Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1-2) in the Context of Breast Conserving Therapy: First Results Following Commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial.

54 : Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

55 : Identification and Resection of Clipped Node Decreases the False-negative Rate of Sentinel Lymph Node Surgery in Patients Presenting With Node-positive Breast Cancer (T0-T4, N1-N2) Who Receive Neoadjuvant Chemotherapy: Results From ACOSOG Z1071 (Alliance).

56 : Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients: a study of 115 cases with cytologic-histologic correlation.

57 : The critical role of axillary ultrasound and aspiration biopsy in the management of breast cancer patients with clinically negative axilla.

58 : Axillary lymph nodes: US-guided fine-needle aspiration for initial staging of breast cancer--correlation with primary tumor size.

59 : Scientific Presentation Award: The combination of axillary ultrasound and ultrasound-guided biopsy is an accurate predictor of axillary stage in clinically node-negative breast cancer patients.

60 : Use of ultrasound-guided axillary node core biopsy in staging of early breast cancer.

61 : Axillary lymph nodes suspicious for breast cancer metastasis: sampling with US-guided 14-gauge core-needle biopsy--clinical experience in 100 patients.

62 : Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.

63 : Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.

64 : The Evolving Role of Marked Lymph Node Biopsy (MLNB) and Targeted Axillary Dissection (TAD) after Neoadjuvant Chemotherapy (NACT) for Node-Positive Breast Cancer: Systematic Review and Pooled Analysis.

65 : Axillary dissection in breast-conserving surgery for stage I and II breast cancer: a National Cancer Data Base study of patterns of omission and implications for survival.

66 : Axillary treatment for operable primary breast cancer.

67 : Value of axillary dissection in addition to lumpectomy and radiotherapy in early breast cancer. The Breast Carcinoma Collaborative Group of the Institut Curie.

68 : Axillary treatment in conservative management of operable breast cancer: dissection or radiotherapy? Results of a randomized study with 15 years of follow-up.

69 : Randomized clinical trial on the role of axillary radiotherapy in breast conservative management without axillary dissection lesion<1 cm (abstract)

70 : Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.

71 : Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023) [abstract]

72 : [Optimal treatment of the axilla after positive sentinel lymph node biopsy in early invasive breast cancer. Early results of the OTOASOR trial].

73 : Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial.

74 : Impact of immediate versus delayed axillary node dissection on surgical outcomes in breast cancer patients with positive sentinel nodes: results from American College of Surgeons Oncology Group Trials Z0010 and Z0011.

75 : Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011.

76 : Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial.

77 : Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.

78 : Regional Nodal Irradiation in Early-Stage Breast Cancer.

79 : Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.

80 : Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

81 : Axillary nodal metastatic burden in patients with breast cancer with clinically positive axillary nodes.

82 : Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.

83 : Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93.

84 : Elderly breast cancer patients treated by conservative surgery alone plus adjuvant tamoxifen: fifteen-year results of a prospective study.

85 : Can sentinel node biopsy be avoided in some elderly breast cancer patients?

86 : Can sentinel node biopsy be avoided in some elderly breast cancer patients?

87 : Incidence of and risk factors for sentinel lymph node metastasis in patients with a postoperative diagnosis of ductal carcinoma in situ.

88 : Variations in the management of the axilla in screen-detected ductal carcinoma in situ: evidence from the UK NHS breast screening programme audit of screen detected DCIS.

89 : Axillary surgery after neoadjuvant therapy in initially node-positive breast cancer: international EUBREAST survey.

90 : Axillary surgery in node-positive breast cancer.

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