Axillary Dissection over the Years: Where To from Here?

Management of the axilla in breast cancer patients has been a subject of intense debate and controversy. Axillary lymph node status is still considered to be the single most important prognostic indicator in breast cancer patients. Despite a tendency toward a conservative approach for the surgery of primary breast carcinoma, axillary lymph node dissection (ALND) has remained an integral part of breast cancer management for more than a century. Among patients with T1/T2 tumors, up to 70% have a negative axillary dissection, and more than 50% of these node-negative patients develop morbidity related to ALND. It is ironic that the extent, morbidity, and cost of a staging procedure (ALND) is more than that of the surgical treatment of the primary tumor. We must readdress the question of axillary management in breast carcinoma in the light of information gained from the sentinel node biopsy trials around the world. We review the historical milestones and various modalities used for axillary management, discuss the concept of sentinel node biopsy for breast carcinoma, and propose a management plan.     

Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which might be an alternative to axillary lymph node dissection in breast cancer patients?

Axillary lymph node status has limited prognostic significance in breast cancer patients and much improvement can be made. Sentinel lymph node biopsy is emerging as an alternative to axillary lymph node dissection for staging, but its prognostic relevance is still uncertain. Detection of micrometastases in sentinel nodes and bone marrow may provide more information, but the clinical significance still needs to be confirmed by ongoing large trials. In this review, we focus on the possibility of sentinel lymph node biopsy or detection of bone marrow micrometastasis replacing traditional axillary lymph node dissection.     

Endoscopic sentinel node detection with a gamma probe combined with minimally invasive axillary lymph node dissection: a preliminary study.

OBJECTIVE: To investigate the efficacy of videoendoscopic axillary lymph node dissection combined with endoscopic sentinel node detection by gamma probe and preoperative sentinel node imaging. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Four patients with breast cancer. INTERVENTION: Injection of 99mTc-nanocolloid around the tumour. RESULTS: In three patients axillary sentinel nodes were detected both before and after operation. In the remaining one it was not found. In two patients the minimally invasive approach had to be converted to conventional open surgery because of anatomical restrictions. CONCLUSION: We describe a new approach that uses a minimally invasive technique and endoscopic radioguided sentinel node biopsy in patients with breast cancer. The results of this preliminary study warrant further investigation.     

Sentinel Node Biopsy: Standard of Care

Abstract: Sentinel lymph node biopsy (SLNB) is a less invasive alternative to axillary lymph node dissection (ALND) for staging breast cancer. In appropriate women, this procedure can stage the axilla with less extensive surgery and fewer complications. Sentinel node status is accurate in predicting axillary status based on single institutional experiences and confirmed by large multi‐center trials. Non‐sentinel nodes are involved very rarely if the sentinel node is tumor‐free. SLNB enables intense examination of a single lymph node. However, the use of special stains to detect micrometastases is of uncertain clinical significance and is the subject of large trials. Early follow‐up from the John Wayne Cancer Institute experience demonstrates excellent outcome for patients with either micrometastases or tumor‐free nodes. Results from techniques with either blue dye or radioisotope colloid tracer and injection locations at peri‐areolar, peritumoral, or subcutaneous sites are similar. These findings support the biological concept of a single (or very few) sentinel nodes for the entire breast. The sentinel node is more predictive of axillary status than any other tumor prognostic factor. Axillary lymph node dissection is unlikely to reveal nodal metastases when the sentinel node is tumor‐free, and in such cases there is no reason to perform a completion axillary node dissection. Sentinel node biopsy alone without axillary lymph node dissection should now be the standard of care for most clinically node‐negative women with breast cancer.     

Role of axillary surgery in early breast cancer: review of the current evidence

BACKGROUND: Controversy continues to surround the best practice for management of the axilla in patients with early breast cancer (EBC), particularly the clinically negative axilla. The balance between therapeutic and staging roles of axillary surgery (with the consequent morbidity of the procedures utilized) has altered. This is due to the increasing frequency of women presenting with early stage disease, the more widespread utilization of adjuvant chemoendocrine therapy and, more recently, the advent of alternative staging procedures, principally sentinel node biopsy (SNB). The aim of the present review is to critically analyse the current literature concerning the preferred management of the axilla in early breast cancer and make evidence-based recommendations on current management. METHODS: A review was undertaken of the English language medical literature, using MEDLINE database software and cross-referencing major articles on the subject, focusing on the last 10 years. The following combinations of key words have been searched: breast neoplasms, axilla, axillary dissection, survival, prognosis, and sentinel node biopsy. RESULTS: Despite the trend to more frequent earlier stage diagnosis, levels I and II axillary dissection remain the treatment of choice in the majority of women with EBC and a clinically negative axilla. CONCLUSIONS: Sentinel node biopsy has no proven superiority over axillary dissection because no randomized controlled trials have been completed to date. Despite this, SNB will become increasingly utilized due to encouraging results from major centres responsible for its development, and patient demand. Therefore if patients are not being enrolled in clinical trials strict quality controls need to be established at a local level before SNB is allowed to replace standard treatment of the axilla. Unless this is strictly adhered to there is a significant risk of an increase in the frequency of axillary relapse and possible increased understaging and resultant inadequate treatment of patients.     

Surgical management of early stage invasive breast cancer: a practice guideline.

OBJECTIVES: To assess the available evidence on sentinel lymph-node biopsy, and to examine the long-term follow-up data from large randomized phase III trials comparing breast-conserving therapy with mastectomy in order to make recommendations on the surgical management of early invasive breast cancer (stages I and II), including the optimum management of the axillary nodes: for the breast--modified radical mastectomy or breast-conserving therapy; for the axilla--complete axillary node dissection, axillary dissection of levels I and II lymph nodes, sentinel lymph-node biopsy or no axillary node surgery. OUTCOMES: Overall survival, disease-free survival, local recurrence, distant recurrence and quality of life. EVIDENCE: MEDLINE, EMBASE, the Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials and meta-analyses. Two members of the Practice Guidelines Initiative, Breast Cancer Disease Site Group (BCDSG) selected and reviewed studies that met the inclusion criteria. The systematic literature review was combined with a consensus process for interpretation of the evidence to develop evidence-based recommendations. This practice guideline has been reviewed and approved by the BCDSG, comprising surgeons, medical oncologists, radiation oncologists, pathologists, a medical sociologist, a nurse representative and a community representative. BENEFITS, HARMS AND COSTS: Breast-conserving therapy (lumpectomy with levels I and II axillary node dissection, plus radiotherapy) provides comparable overall and disease-free survival to modified radical mastectomy. Levels I and II axillary dissection accurately stages the axilla and minimizes the morbidity of axillary recurrence but is associated with lymphedema in approximately 20% of patients and arm pain in approximately 33%. Currently, there is insufficient data regarding locoregional recurrence and long-term morbidity associated with sentinel-node biopsy to advocate it as the standard of care. Breast-conserving therapy may offer an advantage over mastectomy in terms of body image, psychological and social adjustment but appears equivalent with regard to marital adjustment, global adjustment and fear of recurrence. RECOMMENDATIONS: Women who are eligible for breast-conserving surgery should be offered the choice of either breast-conserving therapy with axillary dissection or modified radical mastectomy. Removal and pathological examination of levels I and II axillary lymph nodes should be the standard practice in most cases of stages I and II breast carcinoma. There is promising but limited evidence to support recommendations regarding sentinel lymph-node biopsy alone. Patients should be encouraged to participate in clinical trials investigating this procedure. VALIDATION: A draft version of this practice guideline and a 21-item feedback questionnaire was circulated to 201 practitioners in Ontario. Of the 131 practitioners who returned the questionnaire, 98 (75%) completed the survey and indicated that the report was relevant to their clinical practice. Eighty (82%) of these practitioners agreed that the draft document should be approved as a practice guideline.     

Sentinel node biopsy in breast cancer: recommendations for surgeons, pathologists, nuclear physicians and radiologists in Australia and New Zealand

BACKGROUND: Assessment of axillary lymph node status is necessary for patients with invasive breast cancer. Sentinel node biopsy is a new minimally invasive technique that may provide accurate assessment of regional lymph node status while limiting the morbidity associated with axillary clearance. METHODS: A workshop conducted in Adelaide in November 1998 aimed to assess current sentinel node mapping and biopsy techniques, and make recommendations regarding its application in the surgical management of early breast cancer in Australia and New Zealand. RESULTS: At the conclusion of the workshop, a consensus was reached regarding indications, exclusions, sentinel node mapping/biopsy technique, nuclear medicine requirements, pathology and safety of sentinel node biopsy in breast cancer. It was agreed that a feasibility study according to an agreed prospective protocol was necessary to validate the technique by breast surgeons. Surgeons that satisfied validation criteria for the feasibility study could then consider a prospective randomized study comparing sentinel node biopsy with standard axillary dissection. CONCLUSIONS: Sentinel node biopsy in breast cancer involves close cooperation between members of a multidisciplinary team including surgeons, nuclear physicians, pathologists and radiologists. Although the technique has the potential to reduce morbidity associated with axillary surgery, surgical performance in this area will need to be closely monitored to ensure that the technique does not fall into disrepute by adversely affecting breast cancer prognosis.     

Lymphatic Mapping and Sentinel Node Biopsy of Operable Breast Cancer

The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.     

Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy

BACKGROUND: Radiolocalization and selective biopsy of the sentinel node to correctly predict the status of remaining lymph nodes may provide an alternative to axillary dissection in selected breast cancer patients with clinically negative lymph nodes. STUDY DESIGN: In a nonrandomized, multicenter clinical trial, gamma probe localization for lymphatic mapping and sentinel node biopsy along with axillary dissection was performed on 75 patients with invasive breast cancer and clinically negative lymph nodes. The accuracy of the sentinel node biopsy to correctly predict the status of the remaining axillary lymph nodes was established through standard pathologic investigation. RESULTS: A sentinel node was identified in 70 of 75 patients with a technical success rate of 93%. Of these 70 patients, 21 (30%) had axillary nodal metastases identified pathologically. Four of these 21 (19%) had sentinel nodes negative for metastases. All 4 false-negative patients had prior excisional biopsies. The false-negative group had a larger mean maximal biopsy dimension than the true-positive group. Eleven of the 21 patients with axillary metastases had a diagnosis made by core needle biopsy with no false negatives. CONCLUSIONS: The accuracy of the sentinel node biopsy in correctly predicting the status of remaining axillary lymph nodes may be limited in patients with large excision before radiolocalization of the sentinel node. Our findings suggest that excisional biopsy should be avoided prior to lymphatic mapping for sentinel node biopsy.     

The importance of sentinel node biopsy in breast surgery

Summary   Background: In breast cancer patients the axillary nodes play an important role because of their predictive potential. But the merits of routine diagnostic axillary dissection have increasingly been questioned in the past few years on account of the resultant postoperative morbidity. Rediscovered and reinstated in the early 1980s, sentinel node biopsy (SNB) raised new hopes for differential staging with minimal morbidity. Methods: Based on a review of the available literature, the current role of sentinel node biopsy and its future perspectives are discussed and critically evaluated. Results: Sentinel node biopsy proved to be a practicable procedure for precise nodal staging in breast cancer patients associated with low postoperative morbidity. Serial sections of the sentinel node and immunohistochemical assays provide detailed information on lymphatic drainage and more precise staging information. As a by-product, sentinel node biopsy has re-opened the debate about the importance of micrometastases. Clearly defined criteria for patient selection, interdisciplinary cooperation, careful documentation and follow-up are the keys to its success. Conclusions: Like breast-salvaging surgery, sentinel node biopsy appears to mark a major advance in the management of breast cancer patients. More insights into the significance of micrometastases and the role of axillary dissection as well as into the usefulness of SNB post-preoperative chemotherapy and in multicentric lesions can be expected.      

Axillary Staging in the Neoadjuvant Setting

Neoadjuvant chemotherapy (NAC) is increasingly being used in the treatment of locally advanced breast cancer as well as for early breast cancer. Axillary lymph node dissection has been the standard method of staging the axilla in the neoadjuvant setting. Since the sentinel lymph node biopsy was introduced in the early 1990s, less invasive approaches to axillary staging in patients undergoing neoadjuvant therapy have been proposed. In this review, we discuss the effects of NAC, the imaging modalities that have been used to evaluate the axillary lymph nodes, and the role and timing of sentinel lymph node biopsy in the neoadjuvant setting. Finally, we propose a treatment algorithm for patients undergoing NAC on the basis of the current data.     

Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs Observation after axillary UltraSouND)

Sentinel lymph node biopsy (SLNB) is the standard approach for axillary staging in patients with early breast cancer. Recent data showed no outcome difference in patients with positive sentinel node between axillary dissection vs no further axillary surgery, raising doubts on the role of SLNB itself. Therefore, a new trial was designed comparing SLNB vs observation when axillary ultra-sound is negative in patients with small breast cancer candidates to breast conserving surgery.     

Why perform randomized clinical trials for sentinel node surgery for breast cancer?

Long-term outcome of sentinel node surgery without axillary dissection has not been established. To that extent the therapeutic outcome of sentinel node surgery is unknown. Two important clinical trials are under way that are designed to compare sentinel node surgery without axillary dissection to axillary dissection. In partnership with the University of Vermont, the National Surgical Adjuvant Breast and Bowel Project is conducting a trial that will primarily compare node negative breast cancer cases. The American College of Surgeons Clinical Oncology Group is conducting a trial that randomizes node positive breast cancer patients. The primary endpoints of these clinical trials are survival, long-term regional control, and morbidity. At the conclusion of these trials it will be established within a narrow confidence interval whether sentinel node surgery alone provides the same important therapeutic benefits as axillary surgery but without the morbidity associated with axillary surgery.     

Can radiotherapy replace axillary dissection for patients with positive sentinel nodes?

The substitution of sentinel node biopsy for axillary dissection for patients with early-stage breast cancer has reduced the morbidity of pathologic axillary nodal staging substantially. However, this has resulted in substantial controversy about how to manage patients with positive sentinel nodes. Radiation therapy has been used for many years instead of or in addition to axillary sampling or axillary dissection. This article will examine parts of this experience relevant to the treatment of patients with positive sentinel node biopsy, the limited data on outcome of patients with a positive sentinel node biopsy who do not undergo completion dissection, and the toxicities of axillary irradiation. Finally, I suggest an overall approach to the management of patients with a positive sentinel node biopsy.     

Management of the axilla in early breast cancer: is it time to change tack?

The standard surgical treatment of the axilla in patients with early breast cancer is about to undergo a radical change. Although axillary dissection is an excellent procedure for both staging and local control, particularly in the clinically positive axilla, it has considerable morbidity and may understage a significant proportion of patients, because it will usually miss micrometastases that can occur in approximately 10% of ‘node negative’ patients. An increasing number of patients whose tumours are either non‐invasive (ductal carcinoma in situ; DCIS), micro‐invasive, tubular cancers or low‐grade T_1a tumours without lymphovascular invasion may be spared axillary surgery because the risk of axillary disease is 0–3%. Many studies, both prospective trials and large retrospective series, show that axillary radiotherapy alone provides similar local control rates to axillary dissection in patients with clinically negative axillas. Primary treatment of the axilla with radiotherapy alone, however, does not allow appropriate staging. Sentinel lymph node biopsy is being increasingly used in patients with breast cancer to provide this information. When a sentinel node is identified it is equal to or better than axillary dissection for staging the axilla and, if the node is positive, it will help select patients who should then proceed to further axillary surgery or axillary radiotherapy. Although sentinel lymph node biopsy is being rapidly adopted in many centres worldwide, the results of randomized controlled trials are needed before it can be recommended as the standard of care.     

Accuracy of Axillary Ultrasound in the Diagnosis of Nodal Metastasis in Invasive Breast Cancer: A Review

Axillary lymph node status is the most important prognostic factor in early-stage breast cancer. Sentinel lymph node biopsy is used to determine the need for axillary node dissection. This technique incurs cost associated with radio-isotope administration and use of the operating room. Accordingly, there is a need to preoperatively identify patients with nodal metastases who can proceed directly to axillary dissection. Axillary ultrasound has increasingly been used to determine nodal status prior to surgery. It has been shown to be a sensitive and specific modality in the detection of nodal metastases. When combined with fine-needle aspiration, the specificity of this modality significantly increases. Here we present a current review of the usefulness of preoperative axillary ultrasound in early and locally advanced breast cancer patients with and without fine-needle aspiration biopsy. Based on this review, we estimate the proportion of patients that can be spared a sentinel lymph node biopsy and the concomitant benefit of axillary ultrasound in terms of cost.     

Sentinel lymph node biopsy in the treatment of breast cancer. Experience in 527 cases

AIM: Knowledge of axillary lymph node status is a key aid to staging and prognosis and it represents a guideline for adjuvant therapy in breast cancer. Despite the morbidity it causes, complete axillary dissection was long the mainstay of treatment. Sentinel lymph node biopsy has proved so reliable in the evaluation of node involvement that axillary node dissection is now generally performed when sentinel node biopsy tests negative. METHODS: In this 3-phase study, 50 patients were enrolled to evaluate the learning curve of sentinel node biopsy (phase 1, September 1997-January 1998); 256 patients (age range 27-81 years) with infiltrative breast cancer (T <3 cm, clinical N0) underwent level 1 lymph node dissection when the sentinel node tested negative at histopathology (phase 2, February 1998-March 2001); 221 patients with T <3 cm underwent dissection of the sentinel node when it tested negative for metastasis (phase 3, April 2001-March 2005). RESULTS: The sentinel node was preoperatively detected in 98.6% of cases after peritumoral and intradermic injection of the radionuclide tracer and intraoperatively in 99% (90% with radio-guided surgery, 10% with vital staining). The sentinel node was positive in 15% of patients with T1 and metastatic in 65%. CONCLUSIONS: Our results are in line with the published data; therefore, the study will go forward to examine the role of the micrometastasis in the sentinel node and of in-transit tumoral cells.     

Sentinel Lymph Node Biopsy in Primary Breast Cancer: Window to Management of the Axilla

In patients with primary breast cancer, several large, randomized prospective trials have shown that sentinel node biopsy (SNB) substantially reduces the morbidity associated with axillary surgery compared with formal axillary lymph node dissection (ALND). Moreover, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial has demonstrated that when the sentinel node reveals no evidence of metastatic disease, then no further ALND is required. Recently, the results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial have challenged the notion that all patients with metastases to the sentinel node require ALND. The results of this trial suggest that in selected sentinel node-positive patients, ALND can be potentially avoided. Yet, some concerns about the ACOSOG Z0011 trial have been raised, and these concerns may have implications in the widespread implementation of the results of this trial. Since the advent of the SNB technology, occult metastases within the sentinel node are frequently observed, and the significance of these findings remains controversial. Finally, this review considers special situations, such as pregnancy and the neoadjuvant setting, where the use of SNB should be applied judiciously. The SNB technology has dramatically improved the quality of life for women with breast cancer, and further modifications of its role in breast cancer treatment should be based on evidence obtained from randomized, controlled trials.     

Can axillary lymph node dissection be omitted in patients with breast cancer and positive sentinel nodes?

Sentinel lymph node biopsy has evolved as the surgical procedure of choice for women with clinically negative axillae, as part of an effort to move toward the less invasive surgical management of breast cancer. Axillary lymph node dissection remains the standard of care for patients with a positive axillary node and was previously performed on all patients with breast cancer prior to the implementation of the sentinel lymph node biopsy. There is, however, controversy regarding whether or not all patients with a positive sentinel lymph node need to undergo completion axillary dissection for either prognostic or therapeutic purposes. This article reviews the literature related to this controversial and evolving topic.     

Lymphatic mapping and sentinel lymphadenectomy for breast cancer

Lymphatic mapping and sentinel lymphadenectomy has become an important tool for axillary lymph node staging in women with early-stage breast cancer. This review examines data regarding the staging accuracy, indications and technical aspects of the procedure, and clinical trials investigating the technique. Multiple studies now confirm that sentinel lymphadenectomy accurately stages the axilla and is associated with less morbidity than axillary dissection. Blue dye, radiocolloid, or both can be used to identify the sentinel node, and several injection techniques may be used successfully. Many patient factors previously thought to affect accuracy of the procedure have now been shown to be of limited significance. The indications for the procedure are expanding, and the histopathologic evaluation of the sentinel node and the role of lymphoscintigraphy have been clarified. Clinical trials are now underway that will determine the prognostic significance of micrometastases and the therapeutic benefit of axillary dissection in women with and without sentinel node metastases. Incorporation of sentinel lymphadenectomy into routine clinical practice will maintain accurate axillary staging with lower morbidity and improved quality of life for women with early-stage breast cancer.