American College Of Surgeons Oncology Group Z0011 Research Articles

Should Palpable Nodes Be Exclusionary in Patients Who Are Otherwise Candidates for ACOSOG Z0011-Type Trials?

Palpable nodes were exclusionary in American College of Surgeons Oncology Group (ACOSOG) Z0011, while SINODAR-ONE excluded those with positive axillary nodes by palpation and ultrasound. To determine whether clinical nodal status should be exclusionary in those fulfilling pathologic criteria for ACOSOG Z0011 and similar trials, this study analyzed the accuracy and implications of clinical nodal positivity. Patients ≥ 18years old with cT1-T2, cN0-cN1, M0 breast cancer were identified in the National Cancer Database between 2004 and 2019. Subset characteristics of cN1 and cN0 were compared with respect to final pathologic nodal status and overall survival (OS). Of 57,823 patients identified, 77.0% were cT1 and 23.0% were cT2. Of the 93.9% of patients who were staged as cN0, 16.7% were pN1; of the remaining 6.1% staged as cN1, 9.6% were found to be pN0. Among cN1/pN0 patients, 14.9% underwent axillary dissection without sentinel node biopsy. There was no difference in adjusted OS for patients staged as cN0 versus cN1 who were found to be pN1 (HR 1.13, 95% CI 0.93-1.37, p = 0.22), a finding that persisted on subset analysis in those with two positive nodes (HR 0.91, 95% CI 0.62-1.33, p = 0.63). Clinical nodal stage does not affect OS in pN1 patients. Clinical nodal assessment can both overstage patients and result in unnecessary axillary surgery. These data suggest that cN1 patients who are otherwise candidates for a Z0011-like paradigm should still be considered eligible. Their final candidacy should be determined by surgical lymph node pathology and not preoperative clinical status.

Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

Avoiding unnecessary intraoperative sentinel lymph node frozen section biopsy of patients with early breast cancer.

PurposeAfter the publication of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial, the rate of axillary lymph node dissection has reduced. Thus, the need for intraoperative frozen section biopsy of sentinel lymph nodes (SLNs) has become controversial. We identified patients for whom intraoperative SLN frozen section biopsy could be omitted and found that frozen section biopsy rate can be reduced.MethodsWe reviewed the records of patients with tumors ≤5 cm in diameter who underwent breast-conserving surgery between January 2013 and December 2019 at Seoul St. Mary’s Hospital. Clinicopathological and imaging characteristics were compared according to number of positive SLNs (0–2 SLNs positive vs. ≥3 SLNs positive).ResultsA total of 1,983 patients were included in this study. Thirty-two patients (1.6%) had at least 3 positive SLNs. Patients with ≥3 positive SLNs had significantly larger tumors and were more frequently high-grade tumors (P < 0.001 and P = 0.002, respectively). Identification of suspicious lymph nodes on imaging studies was also associated with the presence of ≥3 positive SLNs (hazard ratio, 11.54; 95% confidence interval, 4.42–30.10). All patients with none or only 1 suspicious lymph node on any imaging modality (n = 647, 32.6%) had 0–2 positive SLNs. Also, among patients with clinical T1-stage tumors and at least 2 suspicious lymph nodes on only 1 imaging modality (n = 514, 25.9%), only 2 cases had ≥3 positive SLNs.ConclusionWe found that intraoperative SLN frozen biopsy could be omitted in patients using tumor size and axillary lymph node status on imaging modality.

Economic implications of ACOSOG Z0011 trial application into clinical practice at the European Institute of Oncology

Background and objectivesThe American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. Patients and methodsWe compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). ResultsOf 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. ConclusionsApplication of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

ACOSOG Z-0011 criteria impact on axillary surgery for early breast cancer in clinical practice: Evaluation in a retrospective cohort of 1900 patients

BackgroundThere is a trend towards de-escalation in early breast cancer axillary surgery. In the American College of Surgeons Oncology Group (ACOSOG) Z-0011 trial, observation was shown to be non-inferior in terms of overall survival to complementary axillary lymph node dissection (cALND) in patients with up to two sentinel lymph node (SLN) metastases. The study included patients with T1-T2 invasive breast cancer, clinically node negative, undergoing breast-conserving surgery with SLN biopsy, followed by systemic therapy and radiotherapy. The aim of our study was to evaluate the impact of applying these ACOSOG Z-0011 inclusion criteria in routine practice. Patients and methodsThis retrospective observational study was conducted in a French comprehensive cancer center where patients treated for breast cancer with primary surgery were prospectively included between 2010 and 2016. Patients meeting ACOSOG Z-0011 inclusion criteria were analyzed. ResultsAmong the 1900 included patients, 1497 (79 %) met the ACOSOG Z-0011 criteria before surgery. Of these, 390 (20 %) had one or two metastatic SLN and could have avoided cALND. Out of these patients, 319 (81 %) presented cT1 tumors. During the study period, cALND was performed in 320 (82 %) patients and was free of metastases in 80 % of cases, having an impact on eligibility for adjuvant chemotherapy in only 3 (0.8 %) patients. ConclusionsIn situations of primary breast cancer surgery, use of ACOSOG Z-0011 criteria could reduce the rate of cALND by 20 %. Further studies are needed to help select patients for whom abstention from any axillary surgery would be reasonable.

Abstract P4-02-14: Impact of ACOSOG Z0011 trial at University Hospital in Brazil

Abstract Background: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trialwas a milestone in the surgical treatment of the axilla. Its results have made significant contributions in reducing the extent of breast surgery. In Brazil, this new approach was questioned, since the survival of the disease remains lower in the developing countries due to the difficulty in the early diagnosis, delay in the treatment and diagnosis in more advanced stages. Objective: To evaluate the overall survival and locoregional recurrence in patients with sentinel lymph node (SLN) metastatic from breast cancer with or without complete axillary lymph node dissection (ALND) treated at our institution. Methods: This retrospective cohort study evaluated patients with primary invasive breast cancer and clinically negative axilla who underwent lumpectomy and sentinel lymph node dissection (SLND) at the São Paulo Hospital, from February 2008 to December 2018. Patients with metastatic SLN were treated with SLND (group 1) or ALND (group 2). Group 1 was composed by the patients who met the inclusion criteria of ACOSOG Z0011 trial. Group 2 was composed by patients treated previous to the publication or by patients that had exclusion criteria according ACOSOG Z0011 trial. Overall survival was defined as the time relapsed from the date of surgery to death from any cause. Locoregional recurrence was determined by the presence of disease in the breast or ipsilateral lymph nodes in the axilla, supraclavicular, infraclavicular or internal mammary. Survival was analyzed with Kaplan-Meier method and comparison among groups with log-rank. Cox proportional-hazards model were applied. Statistical analysis was performed in SPSS version 20.0 and STATA12, with p value &amp;lt;0.05 considered significant. Results: A total of 415 patients were included in this study, 23.3% (97 patients) were identified as metastatic SLN, 56 patients were treated with SLND only (group 1) and 41 patients with ALND (group 2). The groups were homogeneous in relation to the variables: age group (50 years versus 51 years and over) (p = 0.279), race (p = 0.120), level of education (p = 0.142), pathological diagnosis (p = 0.210), histological grade (p = 0.983), hormonal receptors (p = 0.708), HER2 status (p = 0.695), pT (p = 0.334). Average age was 58.3 years (group 1) and 56.3 years (group 2), p = 0.456; and average tumor size was 1.8 cm (group 1) and 2.2 cm (group 2), p = 0.048. In group 1, the average number of resected lymph nodes was 2.7 and 91% of the cases only 1 lymph node was positive. In group 2, the average number of positive lymph nodes was 3.5 and only 17% had additional axillary disease. The SLND presented 35.7% micrometastasis compared to 2.4% in ALND (p &amp;lt;0.001) and a lower number of capsular extravasation (8.9%), in contrast to 41.5% in the ALND group (p &amp;lt;0.001). In addition, ALND group also had greater axillary involvement as evidenced by axillary pathological staging, with N1 (73.2%), N2 (19.5%), N3 (4.9%) and SLND group with N1 (62.5%) and no cases N2 or N3 (p &amp;lt;0.001). The average survival time, estimated using the Kaplan-Meier model, was 9.18 years (95% CI: 8.47-9.90). There was no difference in overall survival between patients who underwent SLND alone or ALND. The 5-year survival was 80.1% in the SLND and 87.5% in the ALND (p = 0.376). The locoregional recurrence was a rare event, average time of 5 years was 1.8% SLND and 7.7% ALND (p = 0.196). Only 4 locoregional recurrences were described and all occurred within 18 months of follow-up. Conclusions: Overall survival and locoregional recurrence in patients with metastatic axillary sentinel lymph node treated with SLND alone did not differ from those who underwent ALND, corroborating ACOSOG Z0011 data. The omission of axillary lymph node dissection and the implementation of this practice in our service benefits the patients treated with less aggressive surgeries and, potentially, produces lower morbidity. Citation Format: Afonso CelsoPinto Nazário, Simone Elias, Gil Facina, Vanessa Monteiro Sanvido. Impact of ACOSOG Z0011 trial at University Hospital in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-14.

Assessment of prognosis in patients with invasive breast cancer and metastatic sentinel lymph node treated with or without axillary lymphadenectomy

Introduction: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial was a landmark in axillary surgical treatment. Its results brought significant contributions to the reduction of the extension of breast cancer surgery. However, this approach was questioned at first. Objectives: To assess the global survival and the locoregional recurrence in patients with metastatic sentinel lymph node biopsy treated with or without axillary lymphadenectomy (AL). Method: A historical cohort study was carried out with patients with primary invasive breast carcinoma and clinically negative axilla who underwent breast-conserving surgery and SLNB between February 2008 and December 2018. Results: We included 415 patients who were submitted to conserving surgery. In 23.3% (97 patients), SLNB was positive, 56 patients were submitted only to SLNB, and 41 patients were treated with AL. The groups were homogeneous regarding the variables: age group (p=0.279), anatomopathological diagnosis (p=0.210), histological grade (p=0.983), hormone receptor expression (p=0.708), HER 2 expression (p=0.695) and pT (p=0.334). Global survival, in the mean period of 5 years, was 80.1% in the SLNB group, and 87.5% in the AL group (p=0.376). The locoregional recurrence was a rare event; in the mean period of 5 years, there was 1.8% in the SLNB group, and 7.7% in the AL group (p=0.196). Only 4 locoregional recurrences were described, and all took place in up to 18 months of follow-up. Conclusions: Global survival and locoregional recurrence in patients with metastatic axillary sentinel lymph node treated only with sentinel lymph node biopsy did not present differences in relation to patients who underwent axillary lymphadenectomy, which corroborates the data from ACOSOG Z0011. The omission of axillary lymphadenectomy and the implantation of such a practice in our service benefitted the patients treated with less aggressive surgery, and, potentially, with lower morbidity.

Microscopic Extracapsular Extension in Sentinel Lymph Nodes Does Not Mandate Axillary Dissection in Z0011-Eligible Patients

In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). Median patient age was 58years, and median tumor size was 1.7cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Which patients with sentinel node-positive breast cancer after breast conservation still receive completion axillary lymph node dissection in routine clinical practice?

In the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, patients with 1 or 2 tumour-involved sentinel lymph nodes (SLNs) gained no benefit from completion axillary lymph dissection (cALND). We examined implementation of evidence from this trial into routine clinical management. Data were included from patients diagnosed with primary breast cancer in German breast cancer units between 2008 and 2015 and analysed retrospectively from a prospective maintained database. Descriptive analyses assessed time-trend changes in axillary surgery. Factors associated with cALND in patients with 1 or 2 positive SLNs were identified using multivariable logistic regression analysis. Overall, 179 breast cancer units provided data for 188,909 patients, of whom 13,741 (7.3%) had pT1/2cN0M0 invasive breast cancer with 1 or 2 tumour-involved SLNs and underwent breast-conserving surgery and adjuvant radiotherapy. cALND use decreased from 94.6% in 2008 to 46.9% in 2015 (p < 0.001). In multivariable analyses, the following factors were associated with cALND: fewer removed SLNs; two tumour-affected SLNs; younger age; lower annual case volume per hospital; higher tumour grade and lymphovascular invasion. No statistically significant influence was detected for hormone receptor or HER2 status. In our cohort, 7.3% of patients with primary breast cancer met the ACOSOG Z0011 inclusion criteria and could potentially have been spared the morbidity of cALND. cALND tended to be performed in patients with a higher axillary tumour burden. This study shows a shift towards less extensive axillary surgery through rapid implementation of new clinical trial evidence into routine clinical practice.

Survival analysis of early-stage breast cancer patients undergoing axillary lymph node dissection and sentinel lymph node dissection

BackgroundThe American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated equivalent survival in early-stage breast cancer (BC) patients receiving either axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. However, institutional studies have called into question the generalization of these findings outside of a clinical trial. MethodsEarly-stage BC patients diagnosed in 2013, that received lumpectomy with whole-breast irradiation, and underwent either ALND or SLND alone, in National Cancer Database were included. Weighted Kaplan-Meier curves were used to estimate 45-month survival, accounting for demographics, comorbidities, insurance type, cancer and neighborhood characteristics. Results62,184 patients were included, of which 21,892 (35%) underwent ALND. Patients undergoing ALND, compared to SLND, appeared to have slightly lower survival (91.4% vs 95.1%); moreover, even after weighting, a small difference persisted (92.7% vs 94.7%, RR 0.98, 95% CI 0.97, 0.99). ConclusionsSLND is a safe and effective alternative to ALND in BC patients with limited nodal involvement. This study provides additional evidence that the findings of ACOSOG Z0011 are applicable to the larger early-stage BC population.

Surgeon Attitudes Toward the Omission of Axillary Dissection in Early Breast Cancer

The American College of Surgeons Oncology Group (ACOSOG) Z0011 study demonstrated the safety of sentinel node biopsy alone in clinically node-negative women with metastases in 1 or 2 sentinel nodes treated with breast conservation. Little is known about surgeon perspectives regarding when axillary lymph node dissection (ALND) can be omitted. To determine surgeon acceptance of ACOSOG Z0011 findings, identify characteristics associated with acceptance of ACOSOG Z0011 results, and examine the association between acceptance of the Society of Surgical Oncology and American Society for Radiation Oncology negative margin of no ink on tumor and surgeon preference for ALND. A survey was sent to 488 surgeons treating a population-based sample of women with early-stage breast cancer (N = 5080). The study was conducted from July 1, 2013, to August 31, 2015. Surgeons were categorized as having low, intermediate, or high propensity for ALND according to the outer quartiles of ALND scale distribution. A multivariable linear regression model was used to confirm independent associations. Of the 488 surgeons invited to participate, 376 (77.0%) responded and 359 provided complete information regarding propensity for ALND derived from 5 clinical scenarios. Mean surgeon age was 53.7 (range, 31-80) years; 277 (73.7%) were male; 142 (37.8%) treated 20 or fewer breast cancers annually and 108 (28.7%) treated more than 50. One hundred seventy-five (49.0%) recommended ALND for 1 macrometastasis. Of low-propensity surgeons who recommended ALND, only 1 (1.1%) approved ALND for any nodal metastases compared with 69 (38.6%) and 85 (95.5%) of selective and high-propensity surgeons (P < .001), respectively. In multivariable analysis, lower ALND propensity was significantly associated with higher breast cancer volume (21-50: -0.19; 95% CI, -0.39 to 0.02; >51: -0.48; 95% CI, -0.71 to -0.24; P < .001), recommendation of a minimal margin width (1-5 mm: -0.10; 95% CI, -0.43 to 0.22; no ink on tumor: -0.53; 95% CI, -0.82 to -0.24; P < .001), participation in a multidisciplinary tumor board (1%-9%: -0.25; 95% CI, -0.55 to 0.05; >9%: -0.37; 95% CI, -0.63 to -0.11; P = .02), and Los Angeles Surveillance, Epidemiology, and End Results site (-0.18; 95% CI, -0.35 to -0.01; P = .04). This study shows substantial variation in surgeon acceptance of more limited surgery for breast cancer, which is associated with higher breast cancer volume and multidisciplinary interactions, suggesting the potential for overtreatment of many patients and the need for education targeting lower-volume breast surgeons.

Expanding Implementation of ACOSOG Z0011 in Surgeon Practice

BackgroundAfter publication of American College of Surgeons Oncology Group (ACOSOG) Z0011, surgeons at our institution limited axillary surgery to sentinel lymph node dissection (SLND) in 76% of patients meeting trial eligibility criteria. Our study objective was to assess incorporation of the trial data into practice 5 years later. Patients and MethodsPatients with clinical T1-2, N0 invasive breast cancer undergoing breast conserving surgery were included. Comparisons were made between patients who underwent axillary lymph node dissection (ALND) and those that had no further surgery. ResultsA total of 396 patients were included. Twelve percent (48/396) had positive SLNs; ALND was performed in 8% (4/48). Patients who underwent ALND were more likely to have 2 positive SLNs (50%, 2/4 vs. 2%, 1/44; P = .02) and microscopic extranodal extension (75%, 3/4 vs. 18%, 8/44; P = .03) than those that did not undergo ALND. Patients who underwent ALND also had a higher nomogram-predicted probability of having additional positive non-SLNs (53%) than those who had SLND alone (22%) (P = .0002). No patients had intraoperative assessment of SLNs performed. ConclusionsThe practice of omitting ALND in ACOSOG Z0011-eligible patients has expanded over 5 years. Clinicopathologic features continue to impact this decision. Intraoperative SLN assessment is no longer performed.

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype. Patients with cT1-2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1-5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND. The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p<0.001). The radiation therapy use rate was 89.4% after SLNB alone and 89.7% after ALND. In the multivariate analysis, the uptake of Z0011 recommendations increased over time (2014 vs 2009: odds ratio [OR] 13.02; p < 0.001). Younger patients were less likely to undergo SLNB alone than older patients (age <40 vs ≥70: OR 0.59; p<0.001). Patients with HER2+ (OR 0.89) or triple-negative disease (OR 0.79) (p<0.001) were less likely to undergo SLNB alone than those with luminal subtypes. Among women potentially eligible for ACOSOG Z0011, the use of SLNB alone increased over time in all groups, but the extent of axillary surgery differed by patient age and tumor subtype.

Development of a Nomogram to Predict N2 or N3 Stage in T1-2 Invasive Breast Cancer Patients with No Palpable Lymphadenopathy.

PurposeSubsequent to the American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trials, complete axillary lymph node dissection is not routinely performed, even in cases where metastatic sentinel lymph nodes are detected. We investigated the percentage of N2 or N3 stages in T1–2 invasive breast cancer patients with no lymphadenopathy and developed a nomogram to predict the possibility of N2 or N3 stages in these patients.MethodsWe retrospectively reviewed the charts of invasive breast cancer patients who were clinically N0 stage, but had a positive sentinel or non-sentinel lymph node detected on sentinel lymph node biopsy. The association of potential risk factors with known outcomes (N2 or N3 stages) was tested using logistic regression analysis. Variables with p<0.05 in the multivariate analysis were included in the nomogram. Internal performance validation was carried out using a 5-fold cross validation method.ResultsAmong a total of 1,437 patients, 1,355 patients had stage N1 disease (94.3%), while 82 had stage N2 or N3 disease (5.7%). Multivariate stepwise logistic regression analysis revealed lymphovascular invasion (p=0.008), T2 stage (p=0.026), metastatic lymph node ratio (p<0.001), and perinodal extension (p<0.001) as independent predictors of N2 or N3 stages. A nomogram was developed based on these factors. The area under the curve estimated from the receiver operating characteristic graph was 0.8050 in the model set and 0.8246 in the test set.ConclusionOur nomogram can be employed for the prediction of N2 or N3 stage among cases fulfilling the ACOSOG Z0011 or AMAROS criteria.

Healthcare Costs Reduced After Incorporating the Results of the American College of Surgeons Oncology Group Z0011 Trial into Clinical Practice.

The purpose of our study was to quantitate the changes in axillary lymph node dissection (ALND), frozen section (FS), and the impact on costs after the publication of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial. We compared axillary nodal management and cost data in breast cancer patients who met Z0011 criteria and were treated with lumpectomy and sentinel lymph nodes (SLN) biopsy from 2007 to July 2013. Of 800 patients, 67 (13.5%) and 34 (12.5%) patients in the pre- and post-Z0011 era had 1-2 positive SLN. ALND decreased from 78% to 21% (p < 0.001) after publication of Z0011. The mean overall cost of SLN biopsy was $41,059 per patient, while SLN biopsy with completion ALND was $50,999 (p < 0.001). Intraoperative FS use decreased from 95% to 66% (p = 0.015). Omitting the FS decreased mean costs from $4,319 to $2,036. The application of Z0011 resulted in an overall mean cost savings of $571,653 from 2011 to July 2013. ACOSOG Z0011 significantly impacted axillary management resulting in a 20% reduction in the mean overall cost per patient by omitting ALND. In these patients, intraoperative FS analysis had poor sensitivity (56%) and doubled the cost of pathologic examination. Fewer ALND and intraoperative FS were performed after the publication of ACOSOG Z0011. Eliminating FS and ALND in patients who met Z0011 criteria, results in significant cost savings.

Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial.

The early results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in locoregional recurrence for patients with positive sentinel lymph nodes (SLNs) randomized either to axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. We now report long-term locoregional recurrence results. ACOSOG Z0011 prospectively examined overall survival of patients with SLN metastases undergoing breast-conserving therapy randomized to undergo ALND after SLND or no further axillary specific treatment. Locoregional recurrence was prospectively evaluated and compared between the groups. Four hundred forty-six patients were randomized to SLND alone and 445 to SLND and ALND. Both groups were similar with respect to age, Bloom-Richardson score, Estrogen Receptor status, adjuvant systemic therapy, histology, and tumor size. Patients randomized to ALND had a median of 17 axillary nodes removed compared with a median of only 2 SLNs removed with SLND alone (P < 0.001). ALND, as expected, also removed more positive lymph nodes (P < 0.001). At a median follow-up of 9.25 years, there was no statistically significant difference in local recurrence-free survival (P = 0.13). The cumulative incidence of nodal recurrences at 10 years was 0.5% in the ALND arm and 1.5% in the SLND alone arm (P = 0.28). Ten-year cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P = 0.36). Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

The impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial: An institutional review

BackgroundAxillary dissection (AD) was historically recommended for all patients with breast tumor involvement discovered by sentinel lymph node biopsy (+SLNB). However, after the ACOSOG Z0011 trial, omission of AD became the recommendation for selected patients with a +SLNB. We report the impact of ACOSOG Z0011 on the completion AD rate in patients with +SLNB at our institution. MethodsWe retrospectively reviewed all patients diagnosed with breast cancer between March 2009 and February 2013 (n = 1781). This cohort was divided into two groups: 1) those diagnosed BEFORE Z0011 and 2) those diagnosed AFTER Z0011. We calculated both the percentage of patients with a +SNLB who underwent AD and, from those patients, the percentage who did and did not meet the Z0011 criteria. ResultsThe BEFORE group contained 849 patients; 144 had +SLNB and from those 113 underwent AD. The AFTER group contained 932 patients: 139 had +SLNB and from those 73 underwent AD. The completion AD rate in the BEFORE group was 78.5%, compared to 52.5% in the AFTER group (p < 0.001). From the patients who met the Z0011 criteria, 75.6% of the BEFORE patients underwent AD, compared to only 2.2%% in the AFTER group (p < 0.001). Among those who did not meet the Z0011 criteria, a similar percentage of patients underwent AD in each group (BEFORE 79.8%, AFTER 74.4%, p = 0.384). ConclusionFollowing the publication of the ACOSOG Z0011 trial, we experienced a significant decrease in the completion AD rate among patients with a +SLNB who met the Z0011 inclusion criteria.

A Population-Based Study of the Effects of a Regional Guideline for Completion Axillary Lymph Node Dissection on Axillary Surgery in Patients with Breast Cancer.

Evidence from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial suggests completion axillary lymph node dissection (cALND) after positive sentinel lymph node biopsy (+SLNB) does not improve outcomes in select patients, leading to practice variation. A multidisciplinary group of surgeons, oncologists, and pathologists developed a regional guideline for cALND which was disseminated in August 2012. We assessed the impact of Z0011 and the regional guideline on cALND rates. Consecutive invasive breast cancer cases undergoing SLNB were reviewed at 12 hospitals. Patient, tumor, and process measures were collected for three time periods: TP1, before publication of Z0011 (May 2009-August 2010); TP2, after publication of Z0011 (March 2011-June 2012); and TP3, after guideline dissemination (January 2013-April 2014). Cases were categorized by whether they met the guideline criteria for cALND (i.e. ≤50years, mastectomy, T3 tumor, three or more positive sentinel lymph nodes [SLNs]) or not (e.g. age>50 years, breast-conserving surgery, T1/T2 tumor, and one to two positive SLNs). The SLNB rate increased from 56% (n=620), to 70% (n=774), to 78% (n=844) in TP1, TP2, and TP3, respectively. Among cases not recommended for cALND using the guideline criteria, cALND rates decreased significantly over time (TP1, 71%; TP2, 43%; TP3, 17%) [p<0.001]. The cALND rate also decreased over time among cases recommended to have cALND using the guideline criteria (TP1, 92%; TP2, 69%; TP3, 58%) [p<0.001]. Based on multivariable analysis, age and nodal factors appeared to be significant factors for cALND decision making. Publication of ACOSOG Z0011 and regional guideline dissemination were associated with a marked decrease in cALND after +SLNB, even among several cases in which the guideline recommended cALND.

Does a Positive Axillary Lymph Node Needle Biopsy Result Predict the Need for an Axillary Lymph Node Dissection in Clinically Node-Negative Breast Cancer Patients in the ACOSOG Z0011 Era?

American College of Surgeons Oncology Group (ACOSOG) Z0011 defined clinical node negativity by physical examination alone. Although axillary ultrasound with biopsy has a positive predictive value for lymph node (LN) metastases approaching 100%, it may not appropriately identify clinically node-negative women with ≥3 positive LNs who require axillary lymph node dissection (ALND). We sought to identify the total number of positive LNs in women presenting with cT1-2N0 breast carcinoma with a positive preoperative LN biopsy to evaluate the potential for overtreatment when ALND is performed on the basis of a positive needle biopsy in patients who otherwise meet ACOSOG Z0011 eligibility criteria. Patients with cT1-2N0 breast cancer by physical examination with a positive preoperative LN biopsy were identified from a prospective institutional database. Clinicopathologic characteristics and axillary imaging results were compared between women with 1 to 2 total positive LNs and ≥3 total positive LNs. Between May 2006 and December 2013, a total of 141 women with cT1-2N0 breast cancer had abnormal axillary imaging and a preoperative positive LN biopsy (median patient age 51years, median tumor size 2.4cm, 86% ductal histology, 79% estrogen receptor positive). Sixty-six women (47%) had 1 to 2 total positive LNs, and 75 (53%) had ≥3 total positive LNs. Women with ≥3 total positive LNs had larger tumors (2.4 vs. 2.2cm, p=0.03), fewer tumors with ductal histology (79 vs. 94%, p=0.01), more lymphovascular invasion (80 vs. 61%, p=0.01), and higher median body mass index (29.2 vs. 27.1kg/m(2), p=0.04). Having >1 abnormal LN on axillary imaging was significantly associated with having ≥3 total positive LNs at final pathology (68 vs. 43%, p=0.003). Axillary imaging with preoperative LN biopsy does not accurately discriminate low- versus high-volume nodal disease in clinically node-negative patients.

The Importance of Applying ACOSOG Z0011 Criteria in the Axillary Management of Invasive Lobular Carcinoma: A Multi-institutional Cohort Study.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial led to a significant change in the management of patients with early stage breast cancer and limited sentinel lymph node (SLN) metastases. However, only 27 patients with invasive lobular carcinoma (ILC) were randomized to the completion axillary lymph node dissection (ALND) arm. To assess the generalizability of the Z0011 trial, the primary aim of this study was to determine the risk of residual nodal burden (RNB) for ILC. A multi-institutional cohort study was completed. RNB was determined for women of any age with an ILC and at least one positive SLN who underwent a primary breast procedure (lumpectomy or mastectomy) and both a SLN biopsy followed by a completion ALND between July 1, 1999, and June 30, 2009, at two large academic centers. A total of 59 patients (60 ILCs) met the inclusion criteria. Although the overall RNB was 40%, it was significantly greater in the T3+ group compared to T1/T2 (87 vs. 24%, respectively, p < 0.0001). When comparing only ILCs that met all of the inclusion criteria for ACOSOG Z0011 (T1 or T2, 1 or 2 SLNs positive, no SLN extranodal extension, and breast conservation) to those ILCs that did not, the RNB was significantly greater in the latter (56 vs. 17 %; p < 0.003). Overall, the clinical practice changes that have occurred after publication of the ACOSOG Z0011 trial appear to be generalizable to ILCs within the inclusion criteria of the study.