We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I–II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3–15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0–50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1–5) in cohort SLND and 18 (range 7–36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.
Sentinel lymph node sampling; Axillary lymph node dissection; Breast cancer; Tangential breast radiotherapy; Radiotherapy
Background and Objectives
Three year post-surgical morbidity levels were compared between patients with negative sentinel lymph node dissection alone (SLND) and those with negative sentinel node dissection and negative axillary lymph node dissection (ALND) in the NSABP B-32 trial.
A total of 1975 ALND and 2008 SLND node negative breast cancer patients had shoulder range of motion and arm volumes assessed along with self reports of arm tingling and numbness. Relative shoulder abduction deficits and relative arm volume differences between ipsilateral and contralateral arms were calculated.
Shoulder abduction deficits ≥ 10% peaked at one week for the ALND (75%) and SLND (41%) groups. Arm volume differences ≥ 10% at 36 months were evident for the ALND (14%) and SLND (8%) groups. Numbness and tingling peaked at 6 months for the ALND (49%, 23%) and SLND (15%, 10%) groups. Logistic regression correlates of residual morbidity included treatment group, age, handedness, tumor size, systemic chemotherapy and radiation to the axilla.
Although residual morbidity for both treatment groups was evident, the results of the NSABP B-32 study indicate the superiority of the SLND compared to the ALND treatment approach relative to post-surgical morbidity outcomes over a three year follow-up period.
shoulder abduction; arm swelling; numbness; tingling
Axillary reverse mapping (ARM) is a new technique to preserve upper extremity lymphatic pathways during axillary lymph node dissection (ALND), thereby preventing lymphedema patients with breast cancer. However, the oncologic safety of sparing the nodes identified by ARM (ARM nodes), some of which are positive, has not been verified. We evaluated the metastatic status of ARM nodes and the efficacy of fine needle aspiration cytology (FNAC) in assessing ARM node metastasis.
Sixty patients with breast cancer who underwent ARM during ALND between January 2010 and July 2012 were included in this study. Twenty-five patients were clinically node-positive and underwent ALND without sentinel lymph node biopsy (SLNB). Thirty-five patients were clinically node-negative but sentinel node-positive on the SLND. The lymphatic pathway was visualized using fluorescence imaging with indocyanine green. ARM nodes in ALND field, whose status was diagnosed using FNAC, were removed and processed for histology. We evaluated the correlation between the cytological findings of FNAC and the histological analysis of excised ARM nodes.
The mean number of ARM nodes identified per patient was 1.6 ±0.9 in both groups. In most patients without (88%) and with (79%) SLNB, the ARM nodes were located between the axillary vein and the second intercostobrachial nerve. FNAC was performed for 45 ARM nodes, 10 of which could not be diagnosed. Six of the patients without SLNB (24%) and onewith SLNB (3%) had positive ARM nodes. Of these sevenpatients, four had >3 positive ARM nodes. There was no discordance between the cytological and histological diagnosis of ARM nodes status.
Positive ARM nodes were observed in the patients not only with extensive nodal metastasis but also in those with a few positive nodes. FNAC for ARM nodes was helpful in assessing ARM nodes metastasis, which can be beneficial in sparing nodes essential for lymphatic drainage, thereby potentially reducing the incidence of lymphedema. However, the success of sampling rates needs to be improved.
Breast cancer; Axillary reverse mapping; Fine needle aspiration cytology; Fluorescence image
The Z11 trial demonstrated a subgroup of patients with low axillary burden who do not benefit from axillary lymph node dissection (ALND) at short-term follow-up when treated with adjuvant whole-breast radiotherapy and systemic therapy. We consider the role of sentinel lymph node biopsy (SLNB) and look at and beyond the Z11 trial to consider further imaging studies, which may offer truly minimally invasive management of the axilla and relegate SLNB to the realms of history.
Regional lymph node status provides information regarding staging, local control, and prognostic outcomes in all cancers. This information was provided in breast cancer by axillary lymph node dissection (ALND). This changed with the development of sentinel lymph node biopsy (SLNB) [1, 2]. Sentinel lymph nodes (SLNs) are defined as the first lymph nodes receiving lymphatic drainage from the primary tumour and therefore the most likely to harbour metastatic cancer via lymphatic spread. SLNB is now the standard of care in patients with a clinically and radiologically clear axilla in early-stage breast cancer.
sentinel lymph node biopsy; axillary lymph node dissection; magnetic resonance imaging; ultrasmall paramagnetic iron oxide
This article reviews the changes in management of the axilla in patients with breast cancer in the last decade. It discusses the recent advances, existing controversies and provides evidence-based guidelines for use in clinical practice.
Sentinel lymph node (SLN) biopsy has replaced the more morbid axillary lymph node dissection (ALND) and four node sampling for axillary nodal staging. Blue dye guided four node sampling is an acceptable alternative when radioisotope facilities are not available. ALND is reserved for patients with proven axillary lymph node involvement.
Preoperative axillary ultrasound and fine-needle aspiration cytology or core biopsy of suspicious lymph nodes reliably identifies around 30% of node positive patients. Intraoperative assessment of the SLN using frozen section or real time molecular assays enables surgeons to perform one stage ALND in node positive patients. For those patients in whom intra-operative SLN assessment is negative, but whose final pathology reveals SLN metastasis, standard treatment has been to perform a completion ALND. Predictive models can be used to identify a lowrisk group of SLN-positive patients in whom routine ALND may not be necessary. In the future, completion ALND for microscopic disease will not be the standard of care but axillary radiotherapy may be an alternative with equal control and less morbidity.
Axillary lymph node dissection; Blue dye; Breast cancer; Four node sampling; Lymphatic mapping; Radioisotope; Sentinel lymph node biopsy
Sentinel lymph node biopsy (SLNB) has become standard of care as a staging procedure in patients with invasive breast cancer. A positive SLNB allows completion axillary lymph node dissection (cALND) to be performed. The axillary recurrence rate (ARR) after cALND in patients with positive SLNB is low. Recently, several studies have reported a similar low ARR when cALND is not performed. This review aims to determine the ARR when cALND is omitted in SLNB-positive patients.
A literature search was performed in the PubMed database with the search terms “breast cancer,” “sentinel lymph node biopsy,” “axillary” and “recurrence.” Articles with data regarding follow-up of patients with SLNB-positive breast cancer were identified. To be eligible, patients should not have received cALND and ARR should be reported.
Thirty articles were analyzed. This resulted in 7,151 patients with SLNB-positive breast cancer in whom a cALND was omitted (median follow-up of 45 months, range 1–142 months). Overall, 41 patients developed an axillary recurrence. 27 studies described 3,468 patients with micrometastases in the SLNB, of whom 10 (0.3 %) developed an axillary recurrence. ARR varied between 0 and 3.7 %. Sixteen studies described 3,268 patients with macrometastases, 24 (0.7 %) axillary recurrences were seen. ARR varied between 0 and 7.1 %. Details regarding type of surgery and adjuvant treatment were lacking in the majority of studies.
ARR appears to be low in SLNB-positive patients even when a cALND is not performed. Withholding cALND may be safe in breast cancer selected patients such as those with isolated tumor cells or micrometastatic disease.
At the first Austrian multidisciplinary expert panel on controversies in local treatment of breast cancer, 22 experts of all relevant disciplines discussed current areas of debate (surgery of the breast, surgery and pathology of the axilla, reconstructive surgery, radiotherapy, and imaging) in local therapy. The most controversial area of debate was the area of axillary surgery. The panel agreed that it was no longer necessary to perform completion axillary lymph node dissection (ALND) when micrometastases are diagnosed in the sentinel lymph node. The only prospective trial comparing patients with sentinel node macrometastases with or without completion ALND had to be terminated early due to failure in sufficient patient recruitment. As long as the frequently discussed issues have not been solved and in light of the lack of any clear level 1 evidence, the panel decided not to recommend omitting axillary dissection in patients with 1 or 2 macrometastases meeting the inclusion criteria of the ACOSOG Z0011 trial. The Austrian panel similarly decided not to recommend omitting axillary dissection in patients with macrometastases and low-risk breast cancer in general. These decisions reflect the increasing skepticism of the scientific community against rapidly shifting paradigms without sufficient and clear evidence.
Breast cancer: local therapy, surgery, radiotherapy; Expert panel
Axillary lymph node involvement is the best prognostic factor for breast cancer survival. Staging breast cancers by axillary dissection remains standard management and is part of the UK national guidelines for breast cancer treatment. In the presence of involved axillary lymph nodes best treatment has been shown to be axillary clearance (Fentiman and Mansell, 1991), but clearly for women whose nodes are uninvolved avoidance of morbidity is optimal and this will be achieved by minimal dissection of the axilla. Thus, for node-negative women the introduction of the sentinel node biopsy technique may revolutionise the approach to the axilla. These will be women with mammographic screen detected small well and moderately differentiated tumours (Hadjiloucas and Bundred, 2000). The impact of sentinel node biopsy in women who have symptomatic large tumours is unproven, and around half of these women will require a second procedure to clear their axilla or radiotherapy as treatment. Even for those women found to have involved sentinel lymph nodes the ability to use early systemic chemotherapy followed by axillary clearance or radiotherapy may provide long-term survival gains. Sentinel node biopsy should not, however, become routine practice until randomised controlled trials have proven its benefit and safety in reducing morbidity. Several randomised controlled trials (including ALMANAC) are currently underway.
British Journal of Cancer (2002) 87, 691–693. doi:10.1038/sj.bjc.6600557 www.bjcancer.com
© 2002 Cancer Research UK
breast cancer; non-axillary sentinel node; treatment
Sentinel node excision has been widely accepted as the initial surgical step for evaluating the axilla for metastatic breast cancer. When the nodes are positive, the standard of care is to complete the axillary node dissection, a more extended procedure that carries an increased risk for morbidity. This article reviews data from sentinel lymph node trials, case series reports of outcomes when axillary node dissection was not performed in the setting of positive sentinel nodes, models for predicting the status of nonsentinel nodes, and the morbidity associated with axillary operations. Despite an approximate 10% false-negative rate, early results indicate that there is a much lower local recurrence rate after sentinel node excision alone and that systemic therapy may sterilize the axilla. In selected patients, it may be appropriate to forgo an axillary node dissection, although there are no randomized clinical trial data to support or refute this suggestion.
The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase III study compares axillary lymph node dissection (ALND) and axillary radiation therapy (ART) in early breast cancer patients with tumor-positive sentinel nodes. In the ART arm, the extent of nodal involvement remains unknown, which could have implications on the administration of adjuvant therapy. In this preliminary analysis, we studied the influence of random assignment to ALND or ART on the choice for adjuvant treatment.
Patients and Methods
In the first 2,000 patients enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic therapy. Multivariate analysis was used to assess variables affecting the administration of adjuvant chemotherapy. Adjuvant therapy was applied according to institutional guidelines.
Of 2,000 patients, 566 patients had a positive sentinel node and were treated per random assignment. There was no significant difference in the administration of adjuvant systemic therapy. In the ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients, respectively, received chemotherapy. Endocrine therapy was administered in 78% (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the patients in the ART arm. Treatment arm was not a significant factor in the decision, and no interactions between treatment arm and other factors were observed. Multivariate analysis showed that age, tumor grade, multifocality, and size of the sentinel node metastasis significantly affected the administration of chemotherapy. Within the ALND arm, the extent of nodal involvement remained not significant in a sensitivity multivariate analysis.
Absence of knowledge regarding the extent of nodal involvement in the ART arm appears to have no major impact on the administration of adjuvant therapy.
The axillary lymph node status is the most important determinant of prognosis in patients with breast cancer. Sentinel lymph node (SLN) biopsy is a safe alternative for axillary clearance with an equal efficacy limiting the morbidity caused by axillary clearance.
Patient and methods
From May 1996 till September 2009, 523 clinically node negative, early breast cancer patients attending our clinic at All India Institute of Medical Sciences were included in the study. They underwent sentinel lymph node biopsy by either combined technique or blue dye alone. All patients irrespective of the axillary status underwent axillary lymph node dissection (ALND).
Of 523 patients, 267 underwent combined technique of sentinel node mapping and 256 underwent blue dye technique alone. The identification rate of sentinel lymph node was 94.3% (253/267) for combined technique and 87.8% (225/256) for blue dye alone. Of 523 patients SLN was identified in 478 patients. The identification rate was 91.3%. The sensitivity = 91.5% (141/154), false negative = 8.4% (13/154), negative predictive value = 96.14% (324/337), and accuracy being 97.2% (465/478).
Sentinel node mapping is a simple and safe technique of identifying the axillary node involvement. Sentinel lymph node biopsy is associated with less arm oedema and shoulder morbidity compared to ALND. However, the results of long term effects of sentinel node approach on tumor recurrence or patient survival are awaited.
Sentinel lymph node biopsy; Axillary lymph node dissection; Axillary node sampling; Lymphatic mapping; Early breast cancer; Immuohistochemistry
Sentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND).
Patients and Methods
At median follow-up of 5 years, lymphedema was assessed in 936 women with clinically node-negative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined.
Of the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P < .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P < .0001). Risk factors associated with measured lymphedema were greater body weight (P < .0001), higher BMI (P < .0001), and infection (P < .0001) or injury (P = .02) in the ipsilateral arm since surgery.
When compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.
This population-based study aimed to analyse variations in surgical treatment and guideline compliance with respect to the application of radiotherapy and axillary lymph node dissection (ALND), for early breast cancer, before and after the sentinel node biopsy (SNB) introduction. The study included 13 532 consecutive surgically treated stage I–IIIA breast cancer patients diagnosed in 1989–2002. Hospitals showed large variation in breast-conserving surgery (BCS) rates, ranging between 27 and 72% for T1 and 14 and 42% for T2 tumours. In multivariate analysis marked inter-hospital and time-dependent variation in the BCS rate remained after correction for case-mix. The guideline adherence was markedly lower for elderly patients. In 25.2% of the patients aged ⩾75 years either ALND or radiotherapy were omitted. The proportion of patients with no ALND after an SNB increased from 1.8% in 1999 to 37.8% in 2002. However, in 2002 also 12.2% of the patients with a positive SNB did not have an ALND. Guideline compliance for BCS, with respect to radiotherapy and ALND, fell since the SNB introduction, from 96.1% before 2000 to 91.4% in 2002 (P<0.001). Noncompliance may however reflect patient-tailored medicine, as for elderly patients with small, radically resected primary tumours. The considerable variation in BCS-rates is more consistent with variations in surgeon preferences than patient's choice.
breast cancer; regional variation; breast-conserving surgery; guideline adherence; sentinel node biopsy
One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient.
In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery.
Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure.
When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer.
Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pcr) information into axillary lymph node restaging after neoadjuvant chemotherapy (nac) adds significance to its prognostic values.
Patients included in the analysis had stage ii or iii disease, with post-nac axillary lymph node dissection (alnd), without sentinel lymph node biopsy before completion of nac, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pcr in both breast and axilla into ypN0(pcr) and ypN0(non-pcr). Univariate and multivariate survival analyses were performed.
Among the 301 patients analyzed, 145 had tumours that were hormone receptor–positive (hr+) and negative for the human epidermal growth factor receptor (her2–), 101 had tumours that were positive for her2 (her2+), and 55 had tumours that were triple-negative. The rate of pcr in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pcr patients, the pcr patients had better disease-free survival (dfs) and overall survival (os): p = 0.002 for dfs and p = 0.011 for os. In non-pcr patients, dfs and os were similar in the ypN0(non-pcr) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pcr) (n = 75), ypN0– 1(non-pcr) (n = 175), and ypN2–3 (n = 51). In those groups, the 3-year dfs was 98%, 91%, and 56%, and the 3-year os was 100%, 91%, and 82% respectively. The differences in dfs and os between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pcr were the only two independent factors predicting dfs.
Axillary lymph node status after nac, adjusted for pcr in breast and axilla, predicts differential dfs in patients without prior sentinel lymph node biopsy.
Breast cancer; neoadjuvant chemotherapy; axillary restaging; pathologic complete response; prognosis
Breast cancer remains a major cause of cancer death for women in the United States. Accurate cancer staging, especially of the axillary lymph nodes, is essential for predicting the prognosis of patients and for determining the appropriate multimodality treatment strategy. Historically, the traditional approach for staging the lymphatic metastasis in breast cancer has been Axillary lymph node dissection (ALND). However, as the understanding of the lymphatic drainage of the breast has improved, the Sentinel lymph node (SLN) biopsy has replaced ALND as the gold standard for lymph node staging in breast cancer. Multiple studies have demonstrated the benefits of SLN biopsy compared to ALND in terms of morbidity, while maintaining the clinical ability to appropriately stage patients, but without any loss in therapeutic impact. In this review, we discuss the historical development of SLN biopsy, describe our technique in detail, and discuss the possible future directions of the lymphatic staging of breast cancer.
Axillary clearance provides important prognostic information but is associated with significant morbidity. Sentinel node biopsy can provide staging .141 patients with node negative early breast cancers-tumour size less than 1.5 cm measured clinically or by imaging had guided axillary sampling (sentinel lymph node biopsy in combination with axillary sampling). Four node axillary sampling improved the detection rate of axillary node metastases by 13.6% as compared to blue dye sentinel node biopsy alone. Positive sampled nodes strongly indicated the likelihood of further metastatic being revealed by axillary dissection (67%). Negative sampled nodes in combination with a positive sentinel node biopsy were associated with a much lower rate of further nodal involvement in the axillary clearance (8%).
Early breast cancer; sentinel node biopsy; axillary sampling; guided axillary sampling
To ensure appropriate axillary surgery is performed at a single operation, we have sought to identify patients with involved nodes who might progress directly to axillary dissection.
PATIENTS AND METHODS
We evaluated pre-operative ultrasound of the axilla and intra-operative frozen section of sentinel lymph nodes over a 3-year period. Patients with clinical early breast cancer underwent axillary ultrasound. Abnormal nodes were defined as a cortex > 2.5 mm, loss of high echogenic medulla, and morphological changes. Any axilla containing a lymph node considered abnormal had ultrasound-directed fine needle aspiration (FNA) performed. Patients with positive cytology proceeded directly to axillary dissection. Patients with negative cytology and those with normal ultrasound proceeded to sentinel four-node biopsy using Patent Blue dye alone. A single sentinel node was evaluated by intra-operative frozen section.
A total of 311 patients underwent pre-operative ultrasound successfully, identifying 115 (77%) patients of the total 150 who were found to have positive lymph nodes. Overall, 196 patients underwent sentinel lymph node biopsy analysis intra-operatively. Of the 11 false negative cases in which the lymph node was found to be positive postoperatively, eight cases showed the single tested sentinel node contained cancer that was recognised on postoperative staining but not frozen section. In six, the deposit in the sentinel node was a micrometastasis. Three cases were found to contain cancer in the ‘non-sentinel' node; in all, this was micrometastatic disease.
This study confirms the value of pre-operative ultrasound and intra-operative frozen section examination of axillary nodes. Only 3.5% of patients required two operations.
Ultrasound; Frozen section; Sentinel lymph node; Breast cancer
The standard treatment of the axilla in breast cancer used to be an axillary lymph node dissection. An axillary lymph node dissection is known to give substantial risks of morbidity. In recent years the sentinel node biopsy has become common practice. Future randomized study results will determine whether the expected decrease in morbidity can be proven.
Before the introduction of the sentinel node biopsy, we conducted a study in which 180 women of 50 years and older with T1/T2 cN0 breast cancer were treated with breast conserving therapy. Instead of an axillary lymph node dissection regional radiotherapy was given in combination with tamoxifen (RT-group). The study group was compared with 341 patients, with the same patient and tumour characteristics, treated with an axillary lymph node dissection (S-group).
The treatment groups were comparable, except for age. The RT-group was significantly older than the S-group. The median follow up was 7.2 years. The regional relapse rates were low and equal in both treatment groups, 1.1% in RT-group versus 1.5% in S-group at 5 years. The overall survival was similar; the disease free survival was significant better in the RT-group.
Regional recurrence rates after regional radiotherapy are very low and equal to an axillary lymphnode dissection.
For patients with early breast cancer and lymph node metastasis, axillary treatment is widely recommended. This is either surgical removal of the axillary lymph nodes, or axillary radiotherapy. The rationale for axillary treatment is that it will reduce the risk of recurrence in the axilla, and may improve survival. However, both treatments are associated with adverse effects, such as lymphedema, pain and sensory loss, and are costly to the health services and to patients. With improvements in adjuvant therapy, routine axillary treatment may no longer offer any overall advantage.
To assess the short and long term benefits and adverse effects of routine axillary treatment (axillary lymph node clearance or axillary radiotherapy) for patients with lymph node positive early-stage breast cancer.
Criteria for potentially eligibility for the study will be that the participants are men and women with early breast cancer and lymph nodes with metastasis. The study compares either axillary treatment with no axillary treatment, or axillary node clearance with axillary radiotherapy, and the study is a randomized trial. Primary outcomes are axillary recurrence, disease-free and overall survival. Secondary outcomes include breast or chest wall recurrence, distant metastasis, time to axillary recurrence, axillary recurrence-free survival, arm morbidity, quality of life and health economic costs. The search strategy will include the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) search portal. Two independent reviewers will assess studies for inclusion in the review, assess study quality and extract data. Characteristics of included studies will be described. Meta-analysis will be conducted using ReVman software.
This review addresses an important clinical question, and results will inform clinical practice and health care policy.
The aim of this study was to evaluate the need of axillary staging in breast cancer patients showing exclusive lymphatic drainage to the internal mammary chain (IMC).
A total of 2203 patients treated for breast carcinoma in three participating hospitals between July 2001 and July 2008 were analyzed. Only patients showing drainage to the IMC on preoperative lymphoscintigraphy were included. The number of harvested IMC sentinel lymph nodes (SLNs), axillary SLNs, and metastases were recorded. Finally, the follow-up of this group of patients was analyzed.
In 25/426 patients, drainage was exclusively to the IMC. Exploration of the axilla resulted in the harvesting of blue SLNs in 9 patients (36%) and the retrieval of an enlarged lymph node in 1 patient. In 4 of the remaining 15 patients, an axillary lymph node dissection (ALND) was done. Lymph node metastases were found in 3 patients who had blue axillary SLNs and in 1 patient who underwent ALND. In the 11 patients who had no blue SLNs and no ALND, no axillary recurrences were observed during follow-up (median = 26 months).
Proper staging of the axilla remains crucial in patients showing exclusive drainage to the IMC. When no axillary node can be retrieved, ALND remains subject to discussion.
Our objective was to assess the global cost of the sentinel lymph node detection [axillary sentinel lymph node detection (ASLND)] compared with standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for early breast cancer patients.
Patients and methods:
We conducted a prospective, multi-institutional, observational, cost comparative analysis. Cost calculations were realized with the micro-costing method from the diagnosis until 1 month after the last surgery.
Eight hundred and thirty nine patients were included in the ASLND group and 146 in the ALND group. The cost generated for a patient with an ASLND, with one preoperative scintigraphy, a combined method for sentinel node detection, an intraoperative pathological analysis without lymphadenectomy, was lower than the cost generated for a patient with lymphadenectomy [€2947 (σ = 580) versus €3331 (σ = 902); P = 0.0001].
ASLND, involving expensive techniques, was finally less expensive than ALND. The length of hospital stay was the cost driver of these procedures. The current observational study points the heterogeneous practices for this validated and largely diffused technique. Several technical choices have an impact on the cost of ASLND, as intraoperative analysis allowing to reduce rehospitalization rate for secondary lymphadenectomy or preoperative scintigraphy, suggesting possible savings on hospital resources.
axillary lymphadenectomy; breast cancer; cost; sentinel lymph node
Since the routine clinical use of the sentinel lymph node (SLN) procedure, questions have been raised concerning an increase in the overall percentage of node-positive patients. The goal of our study was to compare the sensitivity of the SLN procedure and the axillary lymph node dissection (ALND) for the identification of positive lymph nodes in breast cancer.
The incidence of axillary node metastasis in SLNB and ALND specimens from patients undergoing operative treatment of a primary breast carcinoma was compared retrospectively.
Logistic regression models were used to analyze the effect of various predictors on the presence of positive lymph nodes. We constructed a multivariate model including the procedure and these predictors that have shown to be related to lymph node involvement in univariate analysis. The probability of finding positive lymph nodes was thus calculated in both groups correcting for relevant predictors of lymph node involvement.
The SLNB group included 830 patients, the ALND group 320. In a multivariate analysis, adjusting for the number of foci, tumor location in the breast, tumor size, LVI, ER, PR, tumor grade and histological subtype, the probability of finding positive lymph nodes was higher with SLNB procedure than with an ALND. However, this difference was not statistically significant (OR 0.7635; CI 0.5334-1.0930, p 0.1404).
For comparable tumors, SLNB procedure is at least as sensitive as ALND for detecting positive lymph nodes.
Sentinel lymph node biopsy; Axillary lymph node dissection; Breast cancer; Lymph nodes
Aims: To determine the minimum number of lymph nodes needed in an axillary lymph node dissection (ALND) specimen to be confident that the axilla is free from metastases.
Methods: The Edinburgh Breast Unit selects patients with large and high grade tumours for ALND; 609 consecutive ALNDs performed between October 1999 and December 2002 were reviewed. Full data about the underlying invasive breast cancer were available for 520 patients. Data were collected regarding number of positive nodes and total number of nodes collected, tumour size and grade, and presence of lymphovascular invasion.
Results: Axillary node metastases were seen in 64% of patients. The mean number of positive nodes found was 3.56, with a mean of 17.9 nodes collected. The highest proportion of patients with lymph node metastases were in the group with 16–20 nodes recovered/specimen (68%); specimens with >20 nodes recovered did not have a higher rate of nodal involvement. There was a significant difference between the proportion of metastasis positive specimens in those with 1–15 nodes recovered (58.5%) and those with 16 or more recovered (69.1%). A linear association test showed a direct correlation between the number of nodes collected and presence of node metastasis (p = 0.0005).
Conclusions: Although there is no minimum number of nodes that should be recovered in an ALND specimen, 16 nodes should be regarded as a target to ensure a high level of confidence that the nodes are negative. Node positivity in an ALND specimen appears to obey the law of diminishing returns.
breast cancer; metastases; lymph nodes
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.
Overall survival, disease-free survival, local recurrence, distant recurrence and quality of life.
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.
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.
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.
The Practice Guidelines Initiative is supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.
Jan. 21, 2003.