Sentinel Node Positive Breast Cancer Research Articles

Radiotherapy in sentinel node-positive breast cancer: results of an international survey

AbstractPurposeThe purpose of this study was to assess the radiotherapy fields being offered to women with a positive sentinel lymph node (SLN) who have not had axillary lymph node dissection (ALND), based on the American College of Surgeons Oncology Group Z11 results.MethodsWe conducted a postal survey, addressed to radiation oncologists specialising in breast cancer treatment. In total, 179 cancer centres were contacted. Three hypothetical case scenarios were presented. In each case, the patient is clinically node negative but has a positive SLN following breast-conserving surgery, without further ALND. Respondents were asked what radiotherapy fields they would treat with in each scenario.ResultsWe received responses from 90 radiation oncologists from 73 centres in 11 countries. In the three scenarios (low, intermediate and high risk of further lymph node involvement), standard tangential beams would be used by only 27, 12 and 7%, respectively; high tangential beams by 33, 18 and 13%; tangents with full axillary/supraclavicular irradiation by 26, 51 and 61%; the remaining 14, 19 and 19% would use a nomogram to aid their decision.ConclusionThis survey describes the lack of consensus regarding the management of the axilla in patients with clinically node-negative breast cancer but a positive sentinel node and who have not had ALND.

Axillary surgery in women with sentinel node-positive operable breast cancer: a systematic review with meta-analyses.

Traditionally, women with node-positive operable breast cancer have received complete axillary lymph node dissection (ALND), which is associated with significant morbidity, but recently less invasive alternatives have been explored. We conducted a systematic review of randomised controlled trials assessing alternative approaches to axillary surgery in patients with pathologically-confirmed sentinel node-positive operable breast cancer. We searched on 16/3/15 the Specialized Register of the Cochrane Breast Cancer group; CENTRAL; MEDLINE; PreMEDLINE; EMBASE; WHO International Clinical Trials Registry Portal; ClinicalTrials.gov; conference proceedings from ASCO and the San Antonio Breast Cancer meetings; checked reference lists and contacted authors to identify relevant studies. Double, independent study sifting, extraction, appraisal and summarising were undertaken using standard Cochrane Collaboration methodology. We included three studies (2020 patients) comparing ALND with sentinel lymph node dissection (SLND) to SLND alone, and two studies (1899 patients) comparing ALND to axillary radiotherapy (aRT). No differences in survival or recurrence were observed between ALND and SLND or aRT, but morbidity may have been increased in ALND, and all the results were subject to different biases, such as recruitment bias, performance bias, and outcome-reporting bias. Whilst it is encouraging that there appears to be no adverse effect on recurrence or survival, it will be appropriate to confirm these findings and provide additional data confirming quality of life effects and long term outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1712-9) contains supplementary material, which is available to authorized users.

Negative axillary clearance in sentinel node positive breast cancer

Negative axillary clearance in sentinel node positive breast cancer

Is SLN Biopsy Alone Safe in SLN Positive Breast Cancer Patients?

The Z0011 trial demonstrated no difference in overall survival (OS) and locoregional recurrence in breast cancer patients with a positive sentinel lymph node (SLN) randomized to axillary lymph node dissection (ALND) or no further surgery. The aim of this study was to evaluate locoregional recurrence in a nonrandomized group of SLN positive patients, in whom cALND was not performed, that were retrospectively categorized by the Z0011 eligibility criteria. From two hospital breast cancer databases consisting of 656 consecutive SLN positive breast cancer patients, 88 patients, who did not undergo cALND, were identified. This population was categorized by the Z0011 inclusion criteria (e.g., eligible versus ineligible) and the groups were compared. Thirty-four patients (38.6%) were retrospectively eligible for omitting cALND according to the Z0011 criteria and 54 (61.4%) were not. The median number of SLNs removed in both groups was 1 (range 1-5). The number of positive SLNs did not differ between the groups. Tumor size was slightly larger in the ineligible group (21 mm versus 19 mm) and 76% of patients in the ineligible group underwent a mastectomy. At a median follow-up of 26 months (range 1-84 months), one axillary recurrence was observed in the ineligible group versus 0 in the eligible group. Axillary recurrence was low, even in patients who did not meet the Z0011 inclusion criteria. Future trials that randomize Z0011 ineligible patients are needed to investigate long-term results.

A Dutch Prediction Tool to Assess the Risk of Additional Axillary Non–Sentinel Lymph Node Involvement in Sentinel Node-Positive Breast Cancer Patients

BackgroundMultiple predictive systems have previously been developed to identify the sentinel lymph node (SLN)-positive patients at low risk of additional axillary non-SLN involvement and for whom completion axillary lymph node dissection (ALND) could be avoided. However, previous studies showed that these tools had poor performance in Dutch patients with breast cancer, probably owing to variations in pathology settings and differences in population characteristics. The aim of the present study was to develop a predictive tool for the risk of non-SLN involvement in a Dutch population with SLN-positive breast cancer. Materials and MethodsThe data from 513 patients with SLN-positive breast cancer at 10 participating hospitals, who had undergone ALND from January 2007 to December 2008 were studied. The uni- and multivariable associations of predictors for non-SLN metastases were analyzed, and a predictive model was developed. The discriminatory ability of the model was measured by the area under the receiver operating characteristic curve (AUC) and the agreement between predicted probabilities and observed frequencies was visualized by a calibration plot. ResultsA predictive model was developed that included the 2 strongest predictors: the size of the SLN metastases in millimeters and the presence of a negative sentinel lymph node. The model showed good discriminative ability (AUC, 0.75) and good calibration over the complete range of predicted probabilities. ConclusionWe have developed a tool to predict additional non-SLN metastases in Dutch patients with SLN-positive breast cancer that is easy to use in daily clinical breast cancer practice.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BackgroundTrials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013–07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy.DesignThis study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up.DiscussionWe hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival.Trial registrationThe BOOG 2013–07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1613-2) contains supplementary material, which is available to authorized users.

A Paradigm Shift in Axillary Breast Cancer Treatment; From “Treat All-Except,” Toward “Treat None-Unless”

The various pitfalls that exist in using predictive systems for sentinel node-positive breast cancer are described, to give insight into the background and building stones of these systems. The aim of this article was to make clinicians aware of these pitfalls before using them in the clinical decision-making process in individual patients with positive sentinel nodes. Besides these pitfalls, the implications concerning the results of the Z0011 trial as presented by Giuliano et al (Giuliano AE, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: The American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010; 252:426-32, discussion 432-3) are addressed, and we point out some important issues for debate, before implementation of the conclusions of that practice-changing trial into daily clinical breast cancer practice.

P107. Can axillary lymph node clearance be avoided in select sentinel lymph node positive patients?

P107. Can axillary lymph node clearance be avoided in select sentinel lymph node positive patients?

P110. Role of the Memorial Sloan Kettering (MSK) nomogram in guiding the management of sentinel node positive breast cancer

P110. Role of the Memorial Sloan Kettering (MSK) nomogram in guiding the management of sentinel node positive breast cancer

HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer.

HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients. We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology. HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001). Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.

171. The long-term prognosis of sentinel lymph node-positive breast cancer patients without axillary dissection

171. The long-term prognosis of sentinel lymph node-positive breast cancer patients without axillary dissection

Questioning the role of axillary node dissection in sentinel node positive early stage breast cancer in the South Eastern Cancer Centre

Axillary node status is a predictor of breast cancer survival. Axillary node dissection (ALND) following positive sentinel node biopsy (SLNB) is challenged by the American College of Surgeons Z0011 trial, where clinically/radiologically node-negative, SLNB positive early stage patients failed to derive therapeutic benefit from ALND at 6 years. To quantify the rates of non-sentinel lymph node positivity after ALND in all breast cancer stages. To assess Z0011 trial result application to an Irish patient population. Retrospective review of a prospectively maintained database of clinically node-negative patients undergoing breast conserving surgery and ALND for a positive SLNB from January 2011 to January 2012. Of 174 new breast cancers diagnosed, 144 underwent surgery of which 127 patients were clinically/radiologically node-negative; 46 patients were SLNB positive; 34 (73.9 %) proceeded to ALND. Of 9 T1 tumours, 3 (33.3 %) had further positive nodes on ALND. Of 24 T2 tumours, 11 (45.8 %) had further positive nodes on ALND. All 3 (100 %) T3/T4 tumours had further positive nodes on ALND. Mean numbers of sentinel and axillary nodes harvested were 2.3 and 15.2, respectively. In the SLNB positive, ALND negative group, 12 of 18 (66.7 %) patients were <60 years versus 14 of 17 (82.4 %) in the SLNB positive, ALND positive group. This may be indicative that younger women have a trend toward node positivity following ALND for a positive SLNB. These data suggest that a significant proportion (41.9 %) of T1/T2 tumours undergoing ALND following positive SLNB have further positive nodes. It may be premature to exclude ALND in patients with T1/T2 tumours following a positive SLNB.

Predictors and Outcomes of Completion Axillary Node Dissection Among Older Breast Cancer Patients

The role of completion axillary lymph node dissection (ALND) for older women who had sentinel lymph node-positive (SLN+) invasive breast cancer is unclear. We examined factors predictive of ALND and the association between ALND, adjuvant chemotherapy administration, and survival. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we reviewed records of women age >65 diagnosed with stage I/II breast cancer from 1998-2005. Adjusted Cox proportional hazards and multivariate logistic regression were used to identify patient and disease variables associated with ALND, and assess association between ALND and all-cause and breast cancer-specific survival. Among SLN+ patients, 88 % underwent ALND. Earlier diagnosis year, greater nodal involvement, younger age, registry location, and larger tumor size were all associated with a significantly higher likelihood of ALND. The ALND in SLN+ patients was not significantly associated with 5-year breast cancer-specific survival (hazard ratio [HR] 1.22, 95 % confidence interval [CI] 0.76-1.96). The SLN+ patients who underwent ALND were more likely to receive adjuvant chemotherapy (odds ratio [OR] 1.8, 95 % CI 1.45-2.24). However, younger age (OR 18.0, 95 % CI 14.4-23.9), estrogen receptor-negative (ER-) status (OR 4.2, 95 % CI 3.4-5.3), and fewer comorbidities (OR 2.6, 95 % CI 1.7-4.0) were all more strongly linked to receipt of chemotherapy. ALND for older patients with SLN+ breast cancer is not associated with improved 5-year all-cause or breast cancer-specific survival. Younger age, fewer comorbidities, and estrogen receptor-negative (ER-) status were more strongly associated with receipt of chemotherapy than ALND. Consideration should be given to omitting ALND in older patients, particularly if findings of ALND will not influence adjuvant therapy decisions.

Optimal treatment of the axilla after positive sentinel lymph node biopsy in early invasive breast cancer. Early results of the OTOASOR trial

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). 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. 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. 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. 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.

Outcomes of sentinel lymph node-positive breast cancer patients treated with mastectomy without axillary therapy.

53 Background: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have a low rate of regional recurrence when treated with breast conserving surgery and radiation. Patients who fit criteria for the ACOSOG Z0011 trial are candidates to avoid completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment, including CLND and/or radiation therapy (XRT). Methods: We utilized an institutional database to identify patients who were treated with a TM for invasive breast cancer and had a positive SLN from 1994-2010. CLND was defined as removal of 10 or more lymph nodes. Clinicopathologic factors were analyzed and the rate of regional recurrence as well as overall and disease-free survival were determined. Results: A total of 730 patients with invasive breast cancer and a positive SLN were treated with TM including 71 patients who did not have CLND or XRT and 27 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The 10-year actuarial rate of regional recurrence was not significantly different for patients who received no further axillary treatment when compared to those who underwent CLND and XRT (4.9% vs 3.1%) or to those who underwent CLND without XRT (4.9% vs 1.4%). Survival was not significantly different between patients who did not receive further axillary treatment compared to those who underwent CLND without XRT or those who underwent both CLND and XRT. Using a nomogram previously developed by our group, the predicted probability of additional non-SLN involvement was significantly lower for patients who did not undergo CLND compared to those who did (10% vs. 23%, p&lt;0.0001). Conclusions: In select patients with early stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.

For Patients with Sentinel Node-Positive Early Breast Cancer, RT as Effective as and Less Toxic than Complete Surgical Axillary Clearance

For Patients with Sentinel Node-Positive Early Breast Cancer, RT as Effective as and Less Toxic than Complete Surgical Axillary Clearance

Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node

Background. Benefit from axillary lymph node dissection in sentinel node positive breast cancer patients is under debate. Based on data from 1820 Danish breast cancer patients operated in 2002–2008, we have developed two models to predict high risk of non-sentinel node metastases when micrometastases or isolated tumor cells are found in sentinel node. The aim of this study was to validate these models in an independent Danish dataset. Material and methods. We included 720 breast cancer patients with micrometastases and 180 with isolated tumor cells in sentinel node operated in 2009–2010 from the Danish Breast Cancer Cooperative Group database. Accuracy of the models was tested in this cohort by calculating area under the receiver operating characteristic curve (AUC) as well as sensitivity and specificity. Results. AUC for the model for patients with micrometastases was comparable to AUC in the original cohort: 0.63 and 0.64, respectively. The sensitivity and specificity for predicting risk of non-sentinel node metastases over 30% was 0.36 and 0.81, respectively, in the validation cohort. AUC for the model for patients with isolated tumor cells decreased from 0.73 in the original cohort to 0.60 in the validation cohort. When dividing patients with isolated tumor cells into high and low risk of non-sentinel node metastases according to number of risk factors present, 37% in the high-risk group had non-sentinel node metastases. Specificity and sensitivity was 0.48 and 0.88, respectively, in the validation cohort when using this cut-point. Conclusion. In this independent dataset, the model for patients with micrometastases was robust with accuracy similar to the original cohort, while the model for patients with isolated tumor cells was less accurate. The models may be used to identify patients where axillary lymph node dissection should still be considered.

Does the Result of Completion Axillary Lymph Node Dissection Influence the Recommendation for Adjuvant Treatment in Sentinel Lymph Node–Positive Patients?

ObjectiveThe Hungarian National Institute of Oncology has just closed a single-center randomized clinical study. The Optimal Treatment of the Axilla–Surgery or Radiotherapy (OTOASOR) trial compares completion axillary lymph node dissection (cALND) with regional nodal irradiation (RNI) in patients with sentinel lymph node-positive (SLN+) primary invasive breast cancer. In the investigational treatment arm, patients received 50 Gy RNI instead of cALND. In these patients we had information only about the sentinel lymph node (SLN) status, but the further axillary nodal involvement remained unknown. The aim of this study was to investigate whether the result of cALND influenced the recommendation for adjuvant treatment in patients with SLN+ breast cancer. Patients and MethodsPatients with SLN+ primary breast cancer were randomized for cALND (arm A, standard treatment) or RNI (arm B, investigational treatment). Adjuvant systemic treatments were given according to the standard institutional protocol, and patients were followed according to the actual institutional guidelines. ResultsBetween August 2002 and June 2009, 474 SLN+ patients were randomized to cALND (arm A, standard treatment = 244 patients) or RNI (arm B, investigational treatment = 230 patients). The 2 arms were well balanced according to the majority of main prognostic factors. However, more patients were premenopausal (34% vs. 27%; P = .095) and had pT2-3 tumors (57% vs. 40%; P = .003) in the completion axillary lymph node dissection (ALND) arm. On the other hand, there were more patients with known human epidermal growth factor receptor type 2 positive tumor (12% vs. 17%, P = .066) in the RNI arm. In the ALND and RNI arms, 78% (190/244) and 69% (159/230), respectively, received chemotherapy (P = .020). Endocrine therapy was administered in 87% (213/244) of the patients in the ALND arm and 89% (204/230) of the patients in the RNI arm (P = .372). Six patients (2.5%) on arm A and 13 patients (5.7%) on arm B received adjuvant trastuzumab treatment (P = not significant). Subgroup analyses explored that more frequent administration of adjuvant chemotherapy in arm A was associated with the higher percentage of premenopausal patients and patients with larger (pT2-3) tumors. ConclusionsThe result of cALND after positive SLN biopsy seems to have no major impact on the administration of adjuvant systemic therapy.

Assessment of nonsentinel node metastases in sentinel node-positive breast cancer

Assessment of nonsentinel node metastases in sentinel node-positive breast cancer

Which Patients with Sentinel Node–Positive Breast Cancer Can Avoid Axillary Dissection?

Sentinel lymph node (SLN) biopsy is standard care for patients with cN0 breast cancer. An extensive literature, including seven randomized trials, has established that patients with negative SLN do not require axillary dissection (ALND), that axillary local recurrence after a negative SLN biopsy is rare, that disease-free and overall survival are unaffected by the addition of ALND to SLN biopsy, and that the morbidity of SLN biopsy is substantially less than that of ALND. It is now clear that many patients with positive SLN do not require ALND. In ACOSOG Z0011, 6-year locoregional control and survival were equivalent with versus without the performance of ALND in cT1-2N0 patients with ≤2 positive SLN treated by breast conservation with whole breast radiation therapy. A small but growing body of data now suggests that ALND may not be required for selected patients outside the Z0011 eligibility criteria, specifically those treated by mastectomy (without post-mastectomy radiation therapy), by partial breast irradiation, and by neoadjuvant chemotherapy. Looking ahead, the principal goals of axillary staging, prognostication, and local control will be accomplished by SLN biopsy for a substantial majority of patients, and the role of ALND will continue to diminish.