Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer

Background After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. Methods Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. Results SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. Conclusions SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.     

Axillary dissection for breast carcinoma. The myth of skip metastasis

The question of what constitutes an adequate axillary dissection for breast cancer remains open for debate. Central to this controversy is whether axillary nodal metastasis occurs in a stepwise fashion or spreads sporadically, creating skip metastases. The therapeutic aim of axillary dissection also must be considered. To resolve this controversy, a prospective study involving 129 patients who underwent complete axillary dissection for breast carcinoma was performed. The tissue from the axillary dissections was divided intraoperatively and sent to the pathologist as two specimens. The first specimen contained all nodes lateral to the pectoralis minor muscle (Level I), whereas the second contained all nodes beneath and medial to the pectoralis minor (Levels II and III). The tissue was analyzed to determine the frequency of skip metastasis. Only two patients, 1.6 per cent of the total group or 3.2 per cent of the positive node group, were found to have a positive node in Level II-III with no metastasis in Level I. A thorough dissection of Level I alone is sufficient to detect more than 98 per cent of all axillary lymph node metastases from breast cancer. Thus, proper staging of the disease can be obtained. When Level I contained positive nodes, the probability of metastatic disease to higher levels was significant (45%), indicating further treatment is necessary in incomplete axillary dissections.     

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.     

Axillary dissection after unsuccessful sentinel lymphadenectomy for breast cancer.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) has been demonstrated to provide sensitive axillary staging for breast cancer. LM/SL has a steep learning curve, and factors associated with unsuccessful LM/SL are not well known. Two hundred sixty patients with breast carcinoma and clinically negative axillae underwent injection of about 5 cm3 of isosulfan blue dye (Lymphazurin, US Surgical Corp, Norwalk, CT) into breast tissue surrounding a cancer or biopsy site. After 5 minutes of breast compression, blue-stained lymph nodes were sought. In 47 patients, no blue nodes were detected; a standard axillary dissection was performed. All 47 patients were women with a mean age of 56 years (range, 34-80). Ductal carcinoma was most common (91.5%). Mean tumor size was 1.99 cm. Axillary dissection yielded a mean of 15.8 lymph nodes (range, 6-35). Sixteen patients (34%) had positive lymph nodes (mean, 7.6; median, 6; range, 1-24). Factors associated with LM/SL difficulty include surgeon inexperience, medial hemisphere primary location, extensive axillary metastases, and extranodal invasion. Inability to identify a sentinel node in a clinically negative axilla is a risk factor for extensive axillary tumor burden. Axillary dissection should be performed for patients with unsuccessful LM/SL, particularly those with lateral hemisphere primaries.     

A comparison of rates of lymph node metastases between patients undergoing sentinel and axillary lymphadenectomy

BACKGROUND: Recommendations regarding credentialing for sentinel lymphadenectomy in the staging of breast cancer emphasize the need for a trial period during which novice surgeons remove both the sentinel lymph node and the axillary packet, to demonstrate acceptably low rates of both operative failure and inaccuracy. METHODS: We initiated sentinel lymph node mapping in our institution without planned axillary dissection. To establish our ability to accurately stage patients using sentinel lymphadenectomy, we compared 225 patients who underwent that procedure and 343 patients previously staged with axillary lymph node dissection. RESULTS: No differences in node positivity were found between the two groups. Among sentinel lymphadenectomy patients, no differences were found between patients in the first and second half of the institutional experience. CONCLUSIONS: We question the need for a trial period of planned axillary node dissection with sentinel lymph node mapping, and review the evidence from other investigators regarding its necessity.     

Axillary lymph node dissection in clinically node-positive breast cancer

Many Japanese surgeons think that clinically node-positive breast cancer is already a systemic disease. However, about 60% of surgeons believe that the survival rate increases with axillary lymph node dissection. Furthermore, 64% of surgeons change the area of axillary lymph node dissection based on the intraoperative diagnosis of lymph node metastases. We analyzed axillary lymph node dissection in clinically node-positive breast cancer using evidence-based medicine. We recommend that the level I and II axillary dissection be the preferred procedure and that the removal of level III axillary nodes is not necessary for staging. However, if grossly positive nodes are identified intraoperatively, a level III dissection should be carried out to maximize local control.     

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.     

Axillary dissection

Axillary dissection remains an important aspect of breast cancer treatment. No other factor has been demonstrated to be of more prognostic significance in breast cancer than the presence or absence of axillary metastases.^12–14 An axillary sampling that excises fewer than 6 nodes is inadequate for staging and should not be substituted for a complete axillary dissection. Note that directed sentinel node biopsy is different than random axillary lymph node sampling, and these 2 procedures should not be confused. Generally, the pathologist will identify and examine some 15 to 25 nodes in an axillary dissection specimen. The absolute number of axillary nodes varies from individual to individual and with the diligence of pathological examination. Recently, it has been our practice to process the axillary nodes for permanent sections, allowing multiple levels of each node to be studied. Cytokeratin staining is also used selectively.As axillary dissection enters its third century, it must continue to provide complete staging information, combined with preservation of function and cosmetic acceptance. The impact of sentinel lymph node biopsy on axillary dissection is currently being defined.¹⁵ However, it is clear that precise, reliable axillary staging information will remain an indispensable part of surgery for primary breast cancer.^16,17     

The role of selective sentinel lymph node dissection in breast cancer

Axillary nodal status continues to be the most statistically significant predictor of survival for patients with breast cancer. Although still providing regional control of axillary disease, axillary dissection is more important as a staging and prognostic tool. Trials are currently underway to investigate the possibility of replacing the current standard treatment of breast cancer, axillary lymph node dissection, with the less invasive lymphatic mapping and sentinel lymph node biopsy. This issue and the technical aspects of sentinel lymph node mapping for breast cancer are discussed in detail in this article.     

Surgical axilla dissection. Technical standard or obsolete method?

Axillary lymph node status remains the single most important prognostic parameter and has crucial therapeutic implications in patients with breast carcinoma. Surgical dissection of the axilla is commonly regarded as the standard procedure of axillary staging, its sensitivity and specificity being 99% and 100%, respectively. Apart from giving reliable information on the individual prognosis axillary dissection also contributes to efficient local tumor control in the axilla, as it reduces the risk of local recurrence to less than 1.4% if more than 10 lymph nodes are removed. Alternative, less or non-invasive axillary staging methods have either not yet been sufficiently standardized (immunoscintigraphy, PET-scan, prediction of axillary lymph node status by means of individual risk factors) or are associated with a considerable risk of false-negative staging (up to 50% of patients with positive axillary lymph nodes are not detected by palpation alone, ultrasonography or CT-scan). The basic principles of axillary sampling and axilloscopic dissection are questionable because the number of lymph nodes removed during these procedures is commonly less than 10. With its sensitivity/specificity being comparable to that of standard axillary dissection sentinel lymph node biopsy represents a highly promising approach which will in the future potentially lead to significant optimization of the clinical management of patients with breast cancer, especially those diagnosed in early stages (T1 a, T1 b and T1 c).     

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 T1a 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.     

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

A rational approach to the local treatment of intraductal breast cancer continues to generate considerable debate. However, the finding of an invasive component in intraductal breast cancer is widely regarded as an appropriate indication for axillary node dissection as part of the local treatment and staging of this disease. Despite this view, the natural history of patients with intraductal breast cancer with foci of microinvasion is poorly defined. Between 1965 and 1988, 41 patients with this pathologic finding of intraductal carcinoma with foci of microinvasion were seen at the UCLA Medical Center. Twenty-three patients presented with mammographic abnormalities, while 17 patients presented with a palpable mass. One patient presented with Paget's disease of the nipple. Thirty-three patients underwent axillary node dissection as part of their local treatment. No lymph node metastases were identified. The median follow-up in 37 patients was 47 months. There have been no local recurrences and no deaths from recurrent breast cancer. Intraductal breast cancer associated with microinvasion appears to be an extremely favorable lesion with minimal risk of nodal metastases.     

The surgical management of breast cancer

The management of breast cancer is highly controversial. Various operations have been performed in different hospitals. This controversy may arise from an incomplete knowledge of the biology of breast cancer. At present, surgeons are highly recommended to perform an adequate surgery which gives the ultimate in local control, does not compromise the chance of cure and gives the best cosmetic and aesthetic results. Recently, the choice of conservative surgery with aggressive radiation therapy versus more adequate surgery, total mastectomy and axillary dissection, is a major controversial problem for primary treatment of operable breast cancer. However, to avoid local recurrence with attendant worry for the patient, conservative surgery should only be indicated for a select group of patients with early breast cancer. At present, there is little doubt that mastectomy and regional lymph node dissection are the most beneficial methods of treatment in all other patients. So, adequate surgery and breast reconstruction are more preferably recommended for ensuring local control and for providing a better psychological impact.     

Axillar lymphadenectomy]

Axillary dissection aims at local tumor control and staging. Among breast cancer, malignant melanoma and other solid malignancies, the nodal status is still the most important predictive and prognostic factor. Today, because of its morbidity, axillary lymphadenectomy is indicated only when the sentinel lymph node is involved by metastasis after histopathologic investigation. The surgical technique of axillary dissection is presented, complications and oncologic outcomes are summarised after dissection for breast carcinoma and malignant melanoma, respectively.     

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.     

Lymphadenektomie der Axilla

Axillary dissection aims at local tumor control and staging. Among breast cancer, malignant melanoma and other solid malignancies, the nodal status is still the most important predictive and prognostic factor. Today, because of its morbidity, axillary lymphadenectomy is indicated only when the sentinel lymph node is involved by metastasis after histopathologic investigation. The surgical technique of axillary dissection is presented, complications and oncologic outcomes are summarised after dissection for breast carcinoma and malignant melanoma, respectively.     

Failure of sentinel lymph node mapping in patients with breast cancer

BACKGROUND: Lymphatic mapping with sentinel lymphadenectomy (SL) has become more widely used as an alternative to axillary dissection for the staging of breast cancer. This study was conducted to evaluate the potential associations of patient and tumor characteristics with the lymphatic mapping failure rate. STUDY DESIGN: Between September 1996 and April 2003, 1,094 breast cancer patients participated in a single-institution prospective SL protocol, which was conducted using technetium 99 m sulfur colloid alone to identify sentinel lymph nodes. During the validation phase, consisting of the first 80 patients, all patients had SL followed by axillary dissection. Beginning with the 81st patient, the standard technique consisted of radiolabeled colloid injection in a peritumoral distribution 16 to 24 hours before the operation, followed by SL alone for node-negative patients. RESULTS: Of 1,094 consecutive patients, 62 (5.7%) did not map. Patients having more than 10 involved lymph nodes had a significantly higher incidence of mapping failure (40.9%) than those who were node-negative (5.3%) (odds ratio = 9.19, p = 0.002). Age was a factor predictive of mapping failure for node-negative patients 70+ years of age (odds ratio = 3.14, p = 0.018). Biopsy technique, tumor size, tumor location, cell type, and surgeon experience were not predictors of mapping failure, regardless of node status. CONCLUSIONS: The lymphatic mapping failure rate was associated with both anatomic and pathologic factors. Patients with extensive nodal involvement had a significantly greater chance of mapping failure. Among node-negative patients, those who were older were more likely to have mapping failure than those who were younger, suggesting that decreased breast density in postmenopausal women might provide an anatomic explanation for nonmapping.     

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??Standard, controversy and consensus of axillary lymph nodes dissection in breast cancer MA Rong, ZHANG Kai. Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
Corresponding author: MA Rong, E-mail: marongw2000@163.com
Abstract There are many effective methods for breast cancer treatment, surgery is the basis of management of breast cancer. Local control is the symbol of a successful operation. Lymph node status is not only the most important factor in predicting survival in breast cancer, but also the guider of further treatment. Axillary lymph node dissection and pathological examination remains standard management of the axilla and assessment of breast cancer patients. For clinical axillary lymph node metastasis patients, axillary lymph node dissection is critical. Sentinel lymph node biopsy has become standard care for management of the axilla in clinical axillary node-negative early breast cancer patients. It is clear that axillary lymph node dissection should be strongly considered in the management of the sentinel lymph node positive axilla. Omission of axillary lymph node dissection for breast cancer patients with 1-2 positive sentinel lymph nodes is still controversial .     

Is sentinel lymph node biopsy more accurate than axillary dissection for staging nodal involvement in breast cancer patients?

Today evaluation of axillary involvement can be routinely performed with the technique of sentinel lymph node biopsy (SLNB). One of the greatest advantages of SLNB is the nearly total absence of local postoperative complications. It is important to understand whether SLNB is better than axillary lymph-node dissection (ALND) for staging axillary nodal involvement. The aim of the study was to evaluate the axillary staging accuracy comparing three different methods: axillary dissection, sentinel node biopsy with the traditional 4-6 sections and sentinel node biopsy with complete analysis of the lymph node. 527 consecutive patients (525 females and 2 males) with invasive breast cancer < or = 3 cm and clinically negative axillary nodes were divided into 3 different groups: group A treated with axillary dissection, group B treated with sentinel nodal biopsy analysed with 4-6 sections, and group C treated with sentinel node biopsy with analysis of the entire node. All patients underwent a quadrantectomy to treat the tumor. Group differences and statistical significance were assessed by ANOVA. The percentages of N+ in group A and group B were 25.80% and 28% respectively, while in the third group it rose to 45%, or almost half the patients. The differences among the three groups were statistically significant (p = 0.02). From our analysis of the data it emerges that axillary dissection and sentinel node biopsy with analysis of 4-6 sections have the same accuracy in staging the nodal status of the axilla; analysis of the entire sentinel lymph node revealed an increased number of patients with axillary nodal involvement, proving more powerful in predicting nodal stage. SLNB with complete examination of the SLN removed can be considered the best method for axillary staging in breast cancer patients with clinical negative nodes. In our study, the percentage of metastases encountered after complete examination of SLN was 45% compared to the accuracy of axillary dissection that was only 25.8%. Moreover, this approach avoids the useless axillary cleaning in about 55-60% of cases, decreasing postoperative morbidity and mortality.     

Sentinel Lymph Node Biopsy for Breast Cancer: Current Controversies

Abstract:   Sentinel lymph node biopsy (SLNB) has replaced the routine level I and II axillary lymph node dissection (ALND) for women with clinically node-negative T1 and T2 breast cancer. Studies have shown that SLNB is highly predictive of axillary nodal status with a false-negative of rate less than 10%. Our purpose was to address some of the ongoing controversies about this procedure, including technical issues, use of preoperative lymphoscintigraphy, internal mammary lymph node biopsy, criteria for patient selection (in intraductal carcinoma?), its staging accuracy, and the clinical approach when a SLNB was found to be negative or positive on pathologic examination. After the revision of the American Joint Committee on Cancer (AJCC) staging system for breast cancer in 2002, the evaluation of internal mammary lymph nodes and determination of micrometastases by hematoxylin-eosin or by immunohistochemistry have become increasingly important in staging of patients. Recent guideline recommendations developed by the American Society of Clinical Oncology (ASCO) Expert Panel in 2005 are also discussed. Long-term follow-up results of ongoing studies will provide more accurate assessment of the prognostic significance of SLNB and its value in the prevention of breast cancer-related morbidity in axillary staging compared to ALND.