Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease

Aim

It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance.

Methods

We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event.

Results

After a median follow-up of 7.0 years (interquartile range 5.4–8.9 years) survival for the series was high (91.3%; 95% CI 90.3–92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy.

Conclusion

Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.     

Recurrence after sentinel lymph node biopsy with or without axillary lymph node dissection in patients with breast cancer

BACKGROUND: A regional nodal recurrence is a major concern after a sentinel lymph node biopsy (SLNB) alone in patients with breast cancer. In this study we investigated patterns and risk factors of regional nodal recurrence after SLNB alone. PATIENTS AND METHODS: Between January 1999 and March 2005, a series of 1,704 consecutive breast cancer cases in 1,670 patients (34 bilateral breast cancer cases) with clinically negative nodes or suspicious nodes for metastasis who underwent SLNB at a single institute (Saitama Cancer Center) were studied. All 1,704 cases were classified based upon presence or absence of a metastatic lymph node, treated with or without axillary lymph node dissection (ALND). The site of first recurrence was classified as local, regional node, or distant. The regional node recurrences were subclassified as axillary, interpectoral, infraclavicular, supraclavicular, or parasternal. RESULTS: After a median follow-up period of 34 months (range, 2-83 months), first recurrence occurred in local sites in 32 (1.9%) cases, regional nodes in 26 (1.5%) cases, and distant sites in 61 (3.6%) cases. In 1,062 cases with negative nodes treated without ALND and 459 cases with positive nodes treated with ALND, 11 (1.0%) and 15 (3.3%) recurred in regional nodes, respectively, and 4 (0.4%) and 2 (0.6%) recurred in axillary nodes, respectively. Of 822 cases of invasive breast cancer with negative nodes treated with SLNB alone, 10 (1.4%) recurred in regional nodes, and 4 (0.5%) recurred in axillary nodes. In the 10 patients with regional nodal failure, all of the tumors were negative for estrogen receptor (ER) and/or progesterone receptor (PR) and were nuclear grade (NG) 3. CONCLUSIONS: The axillary recurrence rate was low in patients treated with SLNB alone. Omitting ALND is concluded to be safe after adequate SLNB. Risk factors for regional nodal failure after SLNB alone are negative hormone receptor status and high NG.     

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.     

Stage migration after introduction of sentinel lymph node dissection in breast cancer treatment in Denmark: a nationwide study

Purpose

To estimate the size and therapeutic consequences of stage migration after introduction of sentinel lymph node dissection (SLND) in breast cancer treatment in Denmark.

Patients and methods

We compared the distribution of lymph node metastases in breast cancer patients operated in 1993-1996 and 2005-2008; before and after introducing SLND. The study was based on data from the national Danish Breast Cancer Cooperative Group (DBCG) database.

Results

We included 24,051 patients in the study; 10,231 patients from the first period and 13,820 from the second period. The proportion of patients having macrometastases was not significantly different in the two periods, whereas the proportion of patients with micrometastases increased from 5.1% to 9.0% (P < 0.0001). However, this only resulted in an estimated change, from 7.8% to 8.8%, in the proportion of patients offered adjuvant systemic treatment due to positive nodal status as the only high-risk criterion, when using today’s criteria for risk-allocation. In addition, we found that negative hormone receptor status was associated to negative nodal status when adjusted for confounders (odds ratios (OR) 0.83, P < 0.0001).

Conclusion

Introduction of SLND in breast cancer treatment in Denmark has resulted in a stage migration on 4% due to identification of more micrometastases. However, this stage migration has only minor impact on patients offered adjuvant systemic treatment because nodal status today is less important in risk-allocation.     

1枚前哨淋巴结阳性早期乳腺癌保腋窝的可行性分析

目的探讨1枚前哨淋巴结（sentinel lymph node,SLN）阳性的早期乳腺癌患者保腋窝（omitting axillary dissection,OAD）的可行性。方法用美蓝作为示踪剂先行乳腺癌前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）,根据快速冰冻病理结果分为SLN阴性组与1枚SLN阳性组,随后两组均行常规腋窝淋巴结清扫（axillary lymph node dissection,ALND）以解剖出非前哨淋巴结（non—sentinellymphnode,NSLN）,比较两组间NSLN的阳性率。结果SLN阴性组30例,1例NSLN阳性,阳性率为3．3％,准确性为96．7％（29／30）;1枚SLN阳性组30例,仅3例NSLN阳性,阳性率为10．0％;两组阳性率差异无统计学意义（X^2=1．071,P=0．612）。全组随访1～48个月,均无区域淋巴结复发。结论1枚SLN阳性的早期乳腺癌患者可考虑OAD。     

Avoidance of axillary lymph node dissection in selected patients with node-positive breast cancer

Aims

Currently, it is standard practice to avoid ALND in patients with negative SLN, whereas this procedure is mandated for those with positive SLN. However, there has been some debate regarding the necessity of complete ALND in all patients with positive SLN. This review article discusses the issues related to eliminating the need for ALND in selected patients with positive nodes.

Methods

A review of the English language medical literature was performed using the MEDLINE database and cross-referencing major articles on the subject, focusing on the last 10 years.

Results

Currently, complete ALND is mandated in patients with SLN macrometastases as well as those with clinically positive nodes. It is not clear whether SLN biopsy is appropriate for axillary staging in patients with initially clinically positive nodes (N1) that become clinically node-negative (N0) after neoadjuvant chemotherapy. Although there is debate regarding whether ALND should be performed in patients with micrometastases in the SLN, it seems premature to abandon ALND in clinical practice. Moreover, it remains unclear whether it is appropriate to avoid complete ALND in patients with ITC-positive SLN alone.

Conclusions

In the absence of data from randomised trials, the long-term impact of SLN biopsy alone on axillary recurrence and survival rate in patients with SLN micrometastases as well as those with ITC-positive SLN remains uncertain. These important issues must be determined by careful analysis of the results of ongoing clinical trials.     

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. PATIENTS AND METHODS: Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. RESULTS: The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. CONCLUSIONS: Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.     

Feasibility of breast MRI after sentinel procedure for breast cancer with superparamagnetic tracers

Rationale

The gold standard for detection of axillary sentinel lymph nodes uses injection of a radioisotope (99Tc Nanocoll). As an alternative to this method, a magnetometer detecting the superparamagnetic tracer Sienna+^® can be applied for detection of sentinel lymph nodes.The goal of this study was to determine whether interpretation of breast MRI is impaired by Sienna+^® tracer residues in the operated breast and axillary lymph nodes after a sentinel procedure using this tracer.

Accuracy of sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with locally advanced breast cancer and clinically positive axillary nodes

Background

Feasibility and accuracy of sentinel node biopsy (SLNB) after the delivery of neo-adjuvant chemotherapy (NAC) is controversial. We here report our experience in NAC-treated patients with locally advanced breast cancer and clinically positive axillary nodes, and compare it with the results from our previous randomized trial assessing SLNB in early-stage breast cancer patients.

Patients and methods

Sixty-four consecutive patients with large infiltrating tumor and clinically positive axillary nodes received NAC and subsequent lymphatic mapping, SLNB and complete axillary lymph node dissection (ALND). The status of the sentinel lymph node (SLN) was compared to that of the axilla.

Results

At least one SLN was identified in 60 of the 64 patients (93.8%). Among those 60 patients, 37 (61.7%) had one or more positive SLN(s) and 23 (38.3%) did not. Two of the patients with negative SLN(s) presented metastases in other non-sentinel nodes. SLNB thus had a false-negative rate, a negative predictive value and an overall accuracy of 5.1%, 91.3% and 96.7%, respectively. All these values were similar to those we reported for SLNB in the settings of early-stage breast cancer.

Conclusion

SLNB after NAC is safe and feasible in patients with locally advanced breast cancer and clinically positive nodes, and accurately predicts the status of the axilla.     

Omission of axillary lymph node dissection in patients with ypN+ breast cancer after neoadjuvant chemotherapy: A retrospective multicenter study (KROG 21-06)

BackgroundWe evaluated the impact of omitting axillary lymph node dissection (ALND) on oncological outcomes in breast cancer patients with residual nodal disease after neoadjuvant chemotherapy (NAC).MethodsThe medical records of patients who underwent NAC followed by surgical resection and had residual nodal disease were retrospectively reviewed. In total, 1273 patients from 12 institutions were included; all underwent postoperative radiotherapy. Axillary surgery consisted of ALND in 1103 patients (86.6%) and sentinel lymph node biopsy (SLNBx) alone in 170 (13.4%). Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed before and after propensity score matching (PSM).ResultsThe median follow-up was 75.3 months (range, 2.5–182.7). Axillary recurrence rates were 4.8% in the ALND group (n = 53) and 4.7% in the SLNBx group (n = 8). Before PSM, univariate analysis indicated that the 5-year OS rate was inferior in the ALND group compared to the SLNBx group (86.6% vs. 93.3%, respectively; P = 0.002); multivariate analysis did not show a difference between groups (P = 0.325). After PSM, 258 and 136 patients were included in the ALND and SLNBx groups, respectively. There were no significant differences between the ALND and SLNBx groups in DFS (5-year rate, 75.8% vs. 76.9%, respectively; P = 0.406) or OS (5-year rate, 88.7% vs. 93.1%, respectively; P = 0.083).ConclusionsSLNBx alone did not compromise oncological outcomes in patients with residual nodal disease after NAC. The omission of ALND might be a possible option for axillary management in patients treated with NAC and postoperative radiotherapy.     

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up

IntroductionIn patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6–14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs).MethodsThis study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory.ResultsAxillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3–12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8–93.2) and 81.0% (95% CI, 77.2–84.2) in the whole cohort, 92.0% (95% CI, 89.0–94.2) and 81.5% (95% CI, 76.9–85.2) in those initially cN0, 89.8% (95% CI, 85.0–93.2) and 80.1% (95% CI, 72.8–85.7) in those initially cN1/2.ConclusionThe 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.     

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a bayesian approach

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.     

Removal of all radioactive sentinel nodes in breast cancer improves the detection of positive sentinel nodes

OBJECTIVE: The aim of this study is to evaluate if it is necessary to remove all the radioactive sentinel lymph nodes (SLNs) not seen on lymphoscintigraphy in order to accurately stage breast cancer patients. MATERIAL AND METHODS: From March 1999 to March 2006, SLN biopsy was performed in 461 patients. All patients were only injected with radioisotope. Lymphoscintigraphy was performed in all the patients. The mean number of SLNs removed was 2.1 (range 1-15). RESULTS: The SLN was positive in 133 patients (28.8%). Lymphoscintigraphy accurately predicted the number of SLNs identified intraoperatively in 243 patients (52.7%). In 175 patients (37.9%) there were more SLNs identified intraoperatively than were seen on lymphos cintigraphy. In 11 (6.2%) of these 175 patients, additional SLNs identified intraoperatively harboured metastasis. Type of injection, need for a second injection, tumour location and age were not identified as statistically significantly associated with additional positive SLNs identified intraoperatively and not seen on lymphoscintigraphy. CONCLUSIONS: Lymphoscintigraphy does not accurately predict the number of SLNs identified intraoperatively, this number being underestimated. Surgeons should remove all radioactive SLNs to improve the detection of positive SLNs.     

Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation

Introduction The usefulness of routine axillary dissection (AD) at levels I–II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only. Method One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000. Results Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients. Conclusion SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.     

Follow-up of sentinel node negative breast cancer patients without axillary lymph node dissection.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy in breast cancer patients at our institution and to report the follow-up status of node-negative patients with removal of only the sentinel node. METHODS: A total of 247 breast cancer patients underwent sentinel node (SN) mapping between June of 1996 and September of 2000. The SN was identified by using a combination of vital blue dye and a radiolabeled colloid. RESULTS: A SN was identified in 227 of 247 patients (91.9%). One hundred forty-five were SN negative, 82 were SN positive. All SN-positive patients underwent axillary dissection of level I and II, whereas 83 patients with a negative SN had SN biopsy only. Median follow-up of these patients at 22 months revealed no axillary recurrence; the morbidity resulting from SN biopsy was negligible. CONCLUSIONS: Although the follow-up is very short, SN biopsy only in node-negative breast cancer patients had no negative impact on the axillary failure rate and resulted in negligible morbidity.     

Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients,a population based multicenter study

Background

The sentinel lymph node procedure is a widely accepted method for staging of patients with early breast cancer. This study evaluates the incidence of axillary relapse after negative sentinel node biopsy in the seven hospitals in the central part of the Netherlands.

Methods

This study concerns all patients with a T1-2 breast carcinoma who were staged with a sentinel lymph node biopsy in one of the hospitals in the region. Patients with a tumour-free sentinel node without additional axillary lymph node dissection and patients with a sentinel node containing micrometastases were prospectively included and data concerning tumour and primary treatment were recorded. After a median follow-up period of 46 months supplementary data were collected of all patients.

Results

Between January 2002 and December 2003, 541 patients underwent a sentinel node biopsy of which the sentinel node was negative for metastatic disease. During the follow-up period three patients were diagnosed with an axillary recurrence. The incidence of axillary relapse after tumour negative sentinel node biopsy in this study is 0.6% (3/541). In 23 patients a distant metastasis developed. An event occurred in 11% of the patients with a micrometastasis in the sentinel node. This was not significantly different from the patients with a tumour-free sentinel node.

Conclusion

The results suggest that the sentinel lymph node procedure as performed in the region Middle Netherlands is a reliable and accurate instrument for staging of patients with early breast cancer. In our study we observed a non-significant different risk of distant disease in case of micrometastases compared to a tumour negative sentinel node.     

Radioactivity thresholds for sentinel node biopsy in breast cancer

AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.     

Controversies in sentinel node biopsy for breast cancer

Sentinel node biopsy for breast cancer patients has recently been applied as a less invasive, highly accurate alternative to axillary lymph node dissection. Numerous studies have shown that sentinel nodes accurately diagnose axillary staging. However, many problems remain to be answered and must be addressed before sentinel node biopsy becomes the standard surgical procedure for patients with breast cancer. We reviewed and discussed here three of these problems; axillary sampling as an alternative to sentinel node biopsy, dye method vs. combination of dye and radiocolloid for sentinel node biopsy, and intraoperative sentinel node examination. Further investigation will continue to be necessary as we learn how to better provide procedure of sentinel node biopsy.     

Lymphatic mapping and sentinel lymph node biopsy in the patients with breast cancer

Axillary lymph node dissection (ALND) is always standard part for a variety of surgical treatments of breast cancer. Knowledge of the status of axillary nodes presents important information for staging and prognosis, but it remains controversial that ALND provides local control of disease and offer survivalbenefit. Some authors have questioned the wisdom of continuing to do ALND, when the risk of axillary metastasis in the early case is small, and the postoperative complications are usuall…