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.     

Second Biopsy of Axillary Sentinel Lymph Node for Reappearing Breast Cancer After Previous Sentinel Lymph Node Biopsy

Background Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. Methods Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. Results In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. Conclusions Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.     

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.     

Sentinel lymph node biopsy in early-stage breast cancer patients: improved survival through better staging?

Purpose

The objective of this review is to summarize the evidence demonstrating that the sentinel lymph node (SLN) procedure is not only associated with significantly less morbidity compared to the axillary dissection, but may also result in better staging and improved patient outcomes.

Methods

A search of MedLine and PubMed articles using the terms “sentinel lymph node biopsy”, “breast cancer”, “staging”, “morbidity”, “survival”, and “outcomes” was conducted.

Results

Breast cancer staging includes axillary evaluation as an integral component. Over the past two decades, sentinel lymph node biopsy has evolved as a technique that has an improved morbidity over traditional axillary dissection. The sentinel node(s) undergo a more intensive pathologic examination than traditional axillary contents. In the node-negative group of patients, this may have led to stage migration and potentially improved disease-free and overall survival.

Conclusion

The SLN procedure is not only associated with significantly less morbidity compared to the axillary lymph node dissection, it may also result in more accurate staging, better axillary tumor control and improved survival.     

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.     

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.     

Axillary recurrence is low in patients with breast cancer who do not undergo completion axillary lymph node dissection for micrometastases in sentinel lymph nodes

Completion axillary lymph node dissection (CLND) is presently the standard of care after a positive sentinel lymph node biopsy (SLNB). We hypothesize that the incidence of axillary recurrence in patients who do not undergo CLND for micrometastases is low, and CLND is not necessary for locoregional control. We performed a retrospective chart review of patients with invasive breast carcinoma and micrometastases detected on SLNB. The Memorial Sloan Kettering Nomogram (MSKN) predicting the likelihood of nonsentinel lymph node (NSN) metastases was compared with the incidence of positive NSN. There were 61 patients identified with a mean follow-up of 70 months. The average tumor size was 2 cm. The median number of positive SLNs was one. Twenty-eight (46%) patients had a CLND; of these, 20 patients had one positive NSN (2 of 28 [7%]) and the mean MSKN score was 12 per cent. There were 33 (54%) patients who had SLNB alone, and their mean MSKN score was 13 per cent. Axillary recurrence in this group was 1.6 per cent. We conclude the incidence of axillary recurrence in patients with micrometastases detected by SLN biopsy who do not undergo CLND is low. The use of a predictive nomogram to estimate likelihood of metastatic disease to NSN may overestimate the actual incidence of positive NSN in patients with micrometastases.     

Sentinel lymph node biopsy in breast cancer: results of intradermal periareolar tracer injection and follow-up of sentinel lymph node-negative patients

Several methods are in use for identification of the sentinel lymph node (SLN) in breast cancer. We set up the hypothesis that intradermal (i.d.) infra-areolar injection of technetium-99m in combination with i.d. injection of patent blue dye lateral to the areola can identify the same lymph node as peritumoral injection, regardless of the location of the tumour. Each of 50 patients with breast cancer (group I) received an i.d. injection of technetium-99m 1cm caudal to the areola. After induction, blue dye was injected intradermally 1cm lateral to the areola. These patients underwent axillary dissection regardless of their lymph node status. The SLN was identified in 96% of these patients. One of them had axillary lymph node metastases even though the SLN was negative (6%). Further 82 patients (group II) underwent SLN identification and removal without further axillary dissection. The duration of mean follow-up for these patients was 28 months (16-39 months). One patient developed axillary recurrence (1%) 24 months after the initial operation. Intradermal periareolar tracer injection is an accurate method of locating the sentinel node. Long-term follow-up of patients who had negative sentinel nodes and did not undergo axillary dissection revealed a low axillary recurrence rate.     

Estadificación ganglionar tras terapia sistémica primaria en mujeres con cáncer de mama y afectación ganglionar al diagnóstico

ObjectiveThe main objective of this study is to analyze the efficacy of combined axillary marking (lymph node clipping and sentinel lymph node biopsy (SLNB)) for axillary staging in patients with primary systemic treatment (PST) and pathologically confirmed node-positive breast cancer at diagnosis. The secondary objective is to determine the impact of lymph node marking in the suppression of axillary lymph node dissection (ALND) in the study group.MethodsWe conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and a SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an ALND. The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement.ResultsEighty one patients met the inclusion criteria. We identified and extirpated the clip/wire-marked node in 80 of 81 patients (98.8%), with SLNB performed successfully in 88,9% of patients. The SLN and wire-marked node matched in 78.9% of patients; 76.2% of patients did not undergo ALND.ConclusionsThe combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and PST offers a high identification rate (98.8%%) and a high correlation between the wire-marked lymph node and the SLN (78.9%%). This procedure has enabled the suppression of ALND in 76.2% of patients.     

Sentinel Node Biopsy Before Neoadjuvant Chemotherapy Spares Breast Cancer Patients Axillary Lymph Node Dissection

Background Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Methods Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Results Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Conclusions Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.     

Can Axillary Node Dissection Be Omitted in a Subset of Patients with Low Local and Regional Failure Rates?

Axillary node dissection (ALND) is the standard of care for patients who have a positive sentinel lymph node (SLN) on sentinel lymph node biopsy (SLNB). We sought to identify a low-risk patient population with positive SLN that may not need cALND. We analyzed SLNB for breast cancer at our institutions between 1999 and 2007. We identified 130 patients who had a positive SLN but did not undergo completion ALND. We evaluated clinical data, adjuvant treatment patterns and intermediate locoregional and distant events. The median patient age was 50; 19% had N0(i+) disease, 53% had micrometastatic (N1mi) disease, and 28% had macrometastasis. Eighty-eight percent of patients underwent radiation therapy; 66 patients (51%) had documented nodal radiation (of these 50 were treated with three fields and 14 with high tangents. Local recurrence in the breast occurred in two patients (2%) and nine patients (7%) developed distant metastases; there were no axillary/nodal recurrences. In this highly selected group of patients who had a positive SLNB but did not undergo cALND, we observed no axillary recurrences.     

Epitrochlear sentinel lymph nodes in melanoma: interval or independent?

Most primary melanomas on the distal upper extremity metastasize to a sentinel lymph node (SLN) in the axillary basin, but occasionally a primary melanoma will drain to the epitrochlear basin. The relationship between tumor-draining axillary and epitrochlear SLNs is unclear. We hypothesize that the epitrochlear SLN functions in an interval manner with the axillary lymph node basin. We queried our melanoma database to identify patients who underwent SLN biopsy for a distal upper-extremity melanoma. Patient demographics, tumor characteristics, patterns of nodal drainage, and incidence of SLN metastasis were analyzed. Of 255 patients identified, 38 (14.9%) had an epitrochlear SLN. Mean Breslow thickness was 2.26 mm. All patients with epitrochlear drainage had concurrent axillary drainage and underwent axillary and epitrochlear SLN biopsies. Of these 38 patients, two (5.2%) had epitrochlear and axillary SLN metastasis, four (10.5%) had epitrochlear metastasis only, four (10.5%) had axillary metastasis only, and the remaining 28 (73.7%) had tumor-free SLNs. The invariable association of epitrochlear and axillary drainage in this study suggests that epitrochlear nodes function in an interval role with the axillary lymph node basin. Therefore we recommend that all patients with a positive epitrochlear SLN undergo completion axillary dissection.     

Life beyond Z11

The ACOSOG Z0011 (Z11) trial demonstrated the presence of a group of breast cancer patients with some residual axillary disease who did not benefit from axillary lymph node dissection (ALND) in the presence of whole breast radiotherapy and systemic therapy at short term follow-up. It is important that further long-term follow-up of this cohort continues. The outcomes of those patients fitting Z11 criteria who do not undergo ALND should be recorded on a prospective register to ensure close observation should any late divergence in overall survival develop. It is also essential that future studies are inclusive of groups excluded from Z11 rather than simply a re-hash of the trial.     

Three–Axillary Lymph Node Sampling for the Prediction of Nonsentinel Node Metastases in Breast Cancer Patients With Sentinel Node Metastases

Background In half of breast cancer patients with positive sentinel nodes, the sentinel nodes are the only metastatic nodes. Such patients have no more metastatic nonsentinel nodes and do not need to undergo axillary lymph node dissection. The purpose of this study was to investigate whether three–axillary lymph node sampling after sentinel node biopsy predicts the status of nonsentinel nodes in patients with sentinel node metastases. Methods Sentinel node biopsy was performed with dye and radioisotope. When the sentinel nodes were diagnosed as metastasis positive by using intraoperative imprint cytology, three–axillary lymph node sampling was performed, followed by axillary lymph node dissection. Results Of 47 cases with positive imprint cytology, 43 (91%) were diagnosed as metastasis positive on their final histological examination and were analyzed. The status of the sampled nodes was significantly associated with the status of nonsentinel nodes (P < .0001). Six (43%) of 14 patients with positive sampled nodes had at least 1 positive remaining node. Only 2 (7%) of 29 patients whose sampled nodes were negative were found to have additional nodal metastases. The sensitivity, specificity, and accuracy of the sampled nodes for the prediction of nonsentinel node metastases were 87.5%, 100%, and 95.3%, respectively. Conclusions We demonstrated that three-node sampling may be useful for predicting the status of nonsentinel nodes and avoiding axillary lymph node dissection in patients with only sentinel node metastases.     

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.     

Incidence of axillary recurrence in 344 sentinel node negative breast cancer patients after intermediate follow-up. A prospective study into the accuracy of sentinel node biopsy in breast cancer patients

Sentinel lymph node biopsy (SLNB) has been validated in the treatment of breast carcinoma and is considered to stage the axilla adequately in this disease. However, long-term follow-up data are scarce. We evaluated the results of SLNB with respect to loco-regional failures in the axilla in SN-negative patients with invasive breast carcinoma and analysed their causal factors. Between 1997 and May 2004, 656 patients without clinically palpable lymph nodes were included in our study. Data with regard to demographics, diagnostics, therapy and follow up were gathered prospectively from all patients. Patients treated after May 2004 were excluded from this study to permit at least one year of follow-up. Out of the 656 patients, 344 patients with a negative sentinel lymph node biopsy did not undergo axillary dissection and were followed up clinically. Median follow up was 43 months. In 3 patients (0.9%) axillary recurrences developed. All three patients subsequently underwent a completion axillary dissection, chemotherapy and radiotherapy. The low rate of clinical axillary recurrence after an intermediate follow up period suggests that a negative SN biopsy accurately reflects the nodal stage in patients with breast cancer.     

Incidence of axillary recurrence in 344 sentinel node negative breast cancer patients after intermediate follow-up. A prospective study into the accuracy of sentinel node biopsy in breast cancer patients

Sentinel lymph node biopsy (SLNB) has been validated in the treatment of breast carcinoma and is considered to stage the axilla adequately in this disease. However, long-term follow-up data are scarce. We evaluated the results of SLNB with respect to loco-regional failures in the axilla in SN-negative patients with invasive breast carcinoma and analysed their causal factors. Between 1997 and May 2004, 656 patients without clinically palpable lymph nodes were included in our study. Data with regard to demographics, diagnostics, therapy and follow up were gathered prospectively from all patients. Patients treated after May 2004 were excluded from this study to permit at least one year of follow-up. Out of the 656 patients, 344 patients with a negative sentinel lymph node biopsy did not undergo axillary dissection and were followed up clinically. Median follow up was 43 months. In 3 patients (0.9%) axillary recurrences developed. All three patients subsequently underwent a completion axillary dissection, chemotherapy and radiotherapy. The low rate of clinical axillary recurrence after an intermediate follow up period suggests that a negative SN biopsy accurately reflects the nodal stage in patients with breast cancer.     

Axillary Lymph Node Recurrence of Papillary Thyroid Microcarcinoma: Report of a Case

We report a case of axillary lymph node recurrence of thyroid papillary microcarcinoma (PMC) in a 51-year-old woman who had undergone thyroidectomy with lymph node dissection 5 years earlier. We performed residual thyroid resection with cervical and bilateral axillary lymph node dissection, and pathological examination revealed well-differentiated papillary carcinoma, with partial poor differentiation. Postoperative radioiodine therapy was ineffective, and the patient died of systemic dissemination of the recurrence 8 months after her second operation. The positive cell rates of proliferating cell nuclear antigen and Ki-67 were clearly higher in the recurrent lymph nodes than in the primary thyroid tumor, suggesting increased cell proliferation in the recurrent lymph nodes. Thyroid papillary carcinoma rarely recurs in the axillary lymph nodes, but its possibility must be kept in mind, especially in patients with remarkable cervical lymph node metastasis and those who undergo extensive lymph node dissection.     

Breast edema in patients undergoing breast-conserving treatment for breast cancer: assessment via high frequency ultrasound

To identify factors that can influence breast edema in women undergoing breast-conserving therapy. Breast edema was assessed clinically and via high frequency ultrasound (HFUS) prior to, during and following radiotherapy. Fifty-four women were assessed. Breast edema was present prior to radiotherapy in patients who had undergone level 2 node dissection or had wound infection after sentinel node dissection. Edema increased during and after radiotherapy and peaked at 4-6 months. The time course of breast edema was related to the extent of nodal dissection, postoperative wound infection and regional radiotherapy. HFUS prior to irradiation was found to be no better than clinical assessment in predicting prolonged parenchymal breast edema but was significantly better at the end of irradiation. Breast edema levels are minimal in patients who do not undergo axillary node dissection or have an uncomplicated sentinel node dissection. Most edema is due to compromise of the draining lymphatics, which relates largely to the extent of axillary node dissection. HFUS appears to be a useful in the research setting in quantifying the effect of techniques that aim to reduce complications such as edema.     

Sentinel lymph node biopsy for sparing axillary dissection in selected patients with breast cancer

Axillary lymph nodal status in breast cancer remains one of the more important prognostic factors. In early breast cancer axillary lymph node metastasis are found only in 10-18%. It can be deduced that in all these patients a complete axillary dissection is an overtreatment. The concept of sentinel lymph node (SN) was applied to breast cancer. Of course if SN examination gives negative findings, the patient will avoid axillary lymphadenectomy. 134 patients with localized breast cancer were evaluated for enrollment into the study. In 40 (29.8%) patients lymphoscintigraphy was performed together with an injection of vital dye to identify the SN, in 94 (70.1%) only vital dye was utilized. The mapping procedure was successful in 129 cases (96.2%). In our study there was concordance between SNs and axillary nodes in 120 out off 124 cases (96.7%). The false-negative rate was 4.8% (4/83). The overall sensitivity of the SN biopsy was 91.1% (41/45), with a negative predictive value of 95.1% (79/83). Five patients had SN negative and they decided do not undergo axillary lymphadenectomy. This study demonstrates that accurate SN identification was obtained combining lymphoscintigraphy and blue dye. Moreover, each method requires a suitable learning curve. After an accurate training, complete axillary lymphadenectomy can be avoided in selected patients.