Impact of Sentinel Lymph Node Biopsy on Management of Older Women With Clinically Node-Negative, Early-Stage, ER+/HER2-, Invasive Breast Cancer: A Systematic Review and Meta-Analysis.

In 2016 the Choosing Wisely guidelines advised against routine performance of a sentinel lymph node biopsy (SLNB) in women ≥ 70 years of age with clinically node negative (cN0), early-stage, oestrogen receptor positive/ human epidermal growth factor receptor 2 negative (ER+/HER2-), invasive breast cancer. The argument in favour of its continued performance is that it may serve as a useful guide for subsequent management. This systematic review was performed in accordance with the PRISMA guidelines. Studies reporting on rate of adjuvant chemotherapy, adjuvant radiotherapy and performance of completion axillary lymph node dissection (cALND) post SLNB in women aged ≥ 65 years with cN0, early-stage, ER+/HER2-, invasive breast cancer were included. A random effects meta-analysis was performed with summary estimates made using the Mantel-Haenszel method. Dichotomous outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Ten retrospective studies across 4 countries. Of 105,514 patients, 15,509 had a positive SLNB and 90,005 had a negative SLNB. On meta-analysis, a positive SLNB was significantly associated with receipt of adjuvant chemotherapy (OR 4.64 (95% CI 3.18, 6.77), P < .00001), adjuvant radiotherapy (1.71 (95% CI 1.18, 2.47), P = .005) and undergoing completion axillary lymph node dissection (OR 68.97 (95% CI, 7.47, 636.88), P = .0002). Adjuvant treatment decisions continue to be influenced by SLNB positivity in the era of the Choosing Wisely guidelines. The effects of a positive SLNB and subsequent treatments on outcomes remain inconclusive. However, it is likely clinicians are continuing to over-investigate and over-treat this cohort.

Does Sentinel Lymph Node Biopsy Influence Subsequent Management Decisions in Women With Breast Cancer ≥ 70 Years Old?

BACKGROUND: There have been ongoing attempts to de-escalate surgical intervention in older breast cancer patients in recent years. However, there remains ongoing hesitancy amongst surgeons to de-implement axillary staging in this cohort. The supporting argument for performing a sentinel lymph node biopsy (SLNB) is that it may guide subsequent management. METHODS: A retrospective review was performed of 356 SLNBs, in 342 women ≥ 70 years of age with invasive breast cancer, between 2014 and 2022 in a single institution. Data were collected on patient and tumor characteristics and subsequent management for all patients and for patients with ER+/HER2-, early-stage disease. RESULTS: Positive SLNB significantly increased likelihood of receiving adjuvant chemotherapy (CTh) in patients aged 70-75 in all clinical subtypes (OR 4.0, 95% CI, 1.6-10; P = .0035). Positive SLNB did not significantly increase likelihood of receiving adjuvant CTh in patients aged 75-80, however, an Oncotype Dx score of ≥ 26 did (OR 34.50, 95% CI, 3.00-455.2; P = .0103). Positive SLNB was significantly associated with receiving adjuvant radiotherapy (RTh) in all patients aged 70-75 (OR 4.5, 95% CI, 2.0-11; P = .0004) and 75-80 (OR 9.7, 95% CI, 2.7-46; P = .0015). In patients aged ≥ 80 years, positive SLNB did not have a significant influence on subsequent treatments. CONCLUSION: In this study, SLNB did not significantly influence subsequent management decisions in patients over 80 and should rarely be performed in this cohort. However, SLNB still had a role in patients aged 70-80 and should be used selectively in this cohort.

Axillary management for early invasive breast cancer patients: Who will truly benefit?

Background: The implementation of sentinel lymph node biopsy (SLNB) and further completion axillary lymph node dissection (cALND) after positive sentinel lymph nodes (SLNs) on early invasive breast cancer patients should be cautiously tailored. Identifying predictors for SLN and non-sentinel lymph node (nSLN) metastases can help surgeons make better surgical decisions. Methods: A retrospective case-control study was designed and a total of 560 eligible patients were enrolled consecutively. They were all diagnosed in our center and received appropriate medical care. According to the metastasis of SLN and nSLN, they were divided into metastatic and non-metastatic groups on two successive occasions to investigate the relationship between clinical factors, pathological factors, hematological factors and lymph node metastasis. Results: In total, 101 (18.04%) patients developed SLN metastases, including 98 patients with macro-metastases and 3 patients with micro-metastases. Out of 97 patients receiving further cALND, 20 patients (20.62%) developed nSLN metastases. Multivariate analysis revealed that "high expression of Ki-67" and "lymphatic invasion" predicted a higher risk of SLN metastasis; and "increased number of positive SLNs" and "increased systemic inflammation index (SII)" predicted a higher risk of nSLN metastasis. Conclusion: Surgery for early invasive breast cancer patients should be more customized and precise. Appropriate axillary management is necessary for patients with the associated predictors.

Determinants for non-sentinel node metastases in primary invasive breast cancer: a population-based cohort study of 602 consecutive patients with sentinel node metastases.

BACKGROUND: Sentinel node biopsy (SNB) is the standard procedure for axillary staging in patients with clinically lymph node negative invasive breast cancer. Completion axillary lymph node dissection (c-ALND) may not be necessary for all patients as a significant number of patients have no further metastases in non-sentinel nodes (non-SN) and c-ALND may not improve survival. The first aim of our study is to identify clinicopathological determinants associated with non-SN metastases. The second aim is to determine the impact of the number of sentinel node (SN) with macro-metastases and the type of SN metastases on metastatic involvement in non-SN. METHODS: This is a retrospective study of 602 patients with primary invasive breast cancer operated on with SNB and c-ALND in Lund and Malmö during 2008-2013. All these patients had micro- and/or macro-metastases in SNs. Information was retrieved from the national Information Network for Cancer Care (INCA). The risk of metastases to non-SNs were analyzed in relation to clinicopathological determinants such as age, screening mammography, tumour size, tumour type, histological grade, estrogen status, progesterone status, HER2 status, multifocality and lymphovascular invasion. Additionally, we compared the association between the number of the SN and the type of metastases in SN with the risk of metastases to non-SNs. Binary logistic regression was used, yielding odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We found that 211 patients (35%) had metastases in non-SNs and 391 patients (65%) had no metastases in non-SNs. Lobular type (18%) of breast cancer (1.73; 1.0 1-2.97) and multifocal (31.3%) tumours (2.20; 1.41-3.44) had a high risk of non-SNs metastases. As compared to only micro-metastases, the presence of macro-metastases in SNs was associated with a high risk of metastases to non-SNs (4.91; 3.01-8.05). The number of SN with macro-metastases, regardless of the number of SNs removed by surgery, increases the risk of finding non-SNs with metastases. The total number of SN removed by surgery had no impact on diagnosis of metastases in non-SNs. No statistically significant associations were observed regarding other studied determinants. CONCLUSION: We conclude in the present study that lobular cancer and multifocal tumours were associated with a high risk of non-SN involvement. The presence of the macro-metastases in SNs and the number of SN with macro-metastases has a positive association with presence of metastases in non-SNs. The total number of SNs removed by surgery had no impact on finding metastases in non-SNs. These factors may be valuable considering whether or not to omit c-ALND.

Can axillary radiotherapy replace axillary dissection for patients with positive sentinel nodes? A systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of axillary radiotherapy (ART) with that of completion axillary lymph node dissection (cALND) in clinically node-negative breast cancer patients with a positive sentinel lymph node. METHODS: A literature search was performed in PubMed, EMBASE and Cochrane Library by using the search terms "breast cancer", "sentinel lymph node biopsy", "axillary radiotherapy" or "regional node irradiation" for articles published between 2004 and 2016. Only randomized controlled trials that included patients with positive sentinel nodes were included in the meta-analysis. RESULTS: Two randomized controlled trials and three retrospective studies were identified. The reported overall survival rate (hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 0.75-1.43, P = 0.365), disease-free survival rate (HR = 1.01, 95% CI: 0.58-1.45, P = 0.144), and axillary recurrence rate (1.2% and 0.4%, and 1.3% and 0.8%, respectively) were similar in both groups. The absence of knowledge on the extent of nodal involvement in the ART group appeared to have no major impact on the administration of adjuvant systemic therapy. CONCLUSIONS: ART is not inferior to cALND in the patients with clinically node-negative breast cancer who had a positive sentinel lymph node. Information obtained by using cALND after SLNB may have no major impact on the administration of adjuvant systemic therapy.

Axillary lymph node dissection on the run?

The standard approach of performing a completion axillary lymph node dissection (cALND) after a positive sentinel node for breast cancer patients is no longer generally accepted. This study applied the criterion of a 27% risk of having residual positive lymph nodes calculated by the MD Anderson nomogram to perform a cALND. This 27% cut-off is based on the number of positive non-sentinels in the Z0011 trial. A cohort of 166 cN0, sentinel positive breast cancer patients was used to validate the MD Anderson nomogram. ROC (Receiver Operating Characteristic) analysis shows an AUC (Area Under the Curve) of 0.76 and an optimal cut-off at 34% risk of positive non- SLNs (sensitivity 86%, specificity 57%). The 27% cut-off has a sensitivity of 88% and a specificity of 41% to detect positive non-sentinels. In a second cohort (N= 114) the 27% cut-off criterion was prospectively applied and appeared to be practice changing. Although we take minimal risk to leave disease behind (2/166 patients >3 positive nodes), 30.7 % in the first cohort and 54.4 % of the patients in the second cohort could be spared a cALND. The Z0011 criteria would have had more impact, omitting 90% of the cALND, but leaves more disease behind. The impact of leaving disease behind on survival remains unanswered but is awaited by long term follow up of large prospective cohort studies.

When is a completion axillary lymph node dissection necessary in the presence of a positive sentinel lymph node?

BACKGROUND: The management of the axilla in the presence of positive sentinel lymph node (SLN) remains controversial. Many centres forgo completion axillary lymph node dissection (cALND) in the presence of micrometastatic disease. The American College of Surgeons Oncology Group (ACOSOG) Z0011 trialists argue for extending this to macrometastasis. The aim of this study was to correlate tumour burden in SLNs with that in the residual lymph node basin to determine the likelihood of residual disease in patients with micro- and macrometastasis in the SLN. METHODS: Patients who underwent cALND following a positive SLN were analysed for histopathological features of the primary tumour and burden of axillary disease. RESULTS: Of 155 patients, 115 (74%) had macrometastases and 40 (26%) micrometastases in the SLNs. Residual axillary disease was detected in 55/155 (35%) patients with macrometastases and 4/40 (10%) with micrometastases. Generally, with increasing size of metastasis in the SLN there was an increasing risk of further disease in residual lymph nodes. Logistic regression analysis showed increased odds ratios for further disease for all groups when compared with the <2mm (micrometastasis) SLN group. CONCLUSION: Patients may be advised to forgo cALND where the SLN contains isolated tumour cells or micrometastasis. Recommendations for proceeding to cALND can be based on the size of metastasis in the SLN, which relates to the risk of further disease in the residual axillary lymph nodes and subsequent regional recurrence.

[Optimal treatment of the axilla after positive sentinel lymph node biopsy in early invasive breast cancer. Early results of the OTOASOR trial]. / Az axilla optimális kezelése pozitív orszemnyirokcsomó esetén korai invazív emlorákban. Az OTOASOR vizsgálat elozetes eredményei.

INTRODUCTION: Sentinel lymph node biopsy alone has become an acceptable alternative to elective axillary lymph node dissection in patients with clinically node-negative early-stage breast cancer. Approximately 70 percent of the patients undergoing breast surgery develop side effects caused by the axillary lymph node dissection (axillary pain, shoulder stiffness, lymphedema and paresthesias). AIM: The current standard treatment is to perform completion axillary lymph node dissection in patients with positive sentinel lymph node biopsy. However, randomized clinical trials of axillary dissection versus axillary irradiation failed to show survival differences between the two types of axillary treatment. The National Institute of Oncology, Budapest conducted a single centre randomized clinical study. The OTOASOR (Optimal Treatment of the Axilla - Surgery or Radiotherapy) trial compares completion axillary lymph node dissection to axillary nodal irradiation in patients with sentinel lymph node-positive primary invasive breast cancer. METHOD: Patients with primary invasive breast cancer (clinically lymph node negative and less than or equal to 3 cm in size) were randomized before surgery for completion axillary lymph node dissection (arm A-standard treatment) or axillary nodal irradiation (arm B-investigational treatment). Sentinel lymph node biopsy was performed by the radio-guided method. The use of blue-dye was optional. Sentinel lymph nodes were investigated with serial sectioning at 0.5 mm levels by haematoxylin and eosin staining. In the investigational treatment arm patients received 50Gy axillary nodal irradiation instead of completion axillary lymph node dissection. Adjuvant treatment was recommended and patients were followed up according to the actual institutional guidelines. RESULTS: Between August 2002 and June 2009, 2106 patients were randomized for completion axillary lymph node dissection (1054 patients) or axillary nodal irradiation (1052 patients). The two arms were well balanced according to the majority of main prognostic factors. Sentinel lymph node was identified in 2073 patients (98.4%) and was positive in 526 patients (25.4%). Fifty-two sentinel lymph node-positive patients were excluded from the study (protocol violation, patient's preference). Out of the remaining 474 patients, 244 underwent completion axillary lymph node dissection and 230 received axillary nodal irradiation according to randomization. The mean length of follow-up to the first event and the mean total length of follow-up were 41.9 and 43.3 months, respectively, and there were no significant differences between the two arms. There was no significant difference in axillary recurrence between the two arms (0.82% in arm A and 1.3% in arm B). There was also no significant difference in terms of overall survival between the arms at the early stage follow-up. CONCLUSIONS: The authors conclude that after a mean follow-up of more than 40 months axillary nodal irradiation may control the disease in the axilla as effectively as completion axillary lymph node dissection and there was also no difference in terms of overall survival.