Surgeons Oncology Group Z0011 Trial Research Articles

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.

De-escalation of axillary surgery in patients outside Z0011 criteria

Over the past 2 decades, axillary surgical management for breast cancer patients has been reshaped after several practice-changing randomized clinical trials provided evidence to support the de-escalation of axillary surgery, specifically the omission of axillary lymph node dissection, for patients with positive axillary lymph nodes. One such practice-changing trial was the American College of Surgeons Oncology Group Z0011 trial, which showed that patients with clinical T1–2 breast tumors and limited nodal disease (1–2 positive sentinel lymph nodes) who underwent upfront breast-conserving therapy could be safely spared the morbidity of axillary lymph node dissection. American College of Surgeons Oncology Group Z0011 has been criticized as several important groups were excluded, such as patients who underwent a mastectomy, patients with >2 positive sentinel lymph nodes, or patients with imaging-detected lymph node metastases. These exclusions have led to unclear guidelines and very difficult management decisions for many patients with breast cancer who are just outside the Z0011 criteria. Several subsequent trials that investigated sentinel lymph node biopsy alone or sentinel lymph node biopsy plus axillary radiation versus axillary lymph node dissection enrolled patients with higher volumes of disease than American College of Surgeons Oncology Group Z0011, such as mastectomy patients or patients with >2 positive sentinel lymph nodes. The goal of this review is to describe the findings of these trials and to discuss the current best practices regarding axillary management in patients who are candidates for upfront surgery but were excluded from American College of Surgeons Oncology Group Z0011, with a particular focus on patients undergoing mastectomy, patients with >2 positive sentinel lymph nodes, patients with large or multifocal tumors, and patients with imaging-detected biopsy-proven lymph node metastases.

Population-Level Impact of Omitting Axillary Lymph Node Dissection in Early Breast Cancer Women: Evidence from an Economic Evaluation in Germany.

The American College of Surgeons Oncology Group Z0011 trial showed that complete axillary lymph node dissection (cALND) did not improve survival benefits in patients with one or two tumour-involved sentinel lymph nodes and undergoing breast conservation. Still, a considerable number of the Z0011-eligible patients continue to be treated with cALND in various countries. Given the potential economic gain from implementation of the Z0011 recommendations, we quantified population-level impacts of omitting cALND among Z0011-eligible patients in clinical practice. This 2-year economic analysis adopted both the perspective of patients under statutory insurance and the societal perspective, using data collected prospectively from 179 German breast cancer units between 2008 and 2015. The estimation of cost savings and health gain relied on a single decision tree, which considered three scenarios: clinical practice at the baseline; actual implementation in routine care; and hypothetical full implementation in all eligible patients. Data for 188,909 patients with primary breast cancer were available, 13,741 (7.3%) of whom met the Z0011 inclusion criteria. The use of cALND decreased from 94.3% in 2010 to 46.9% in 2015, resulting in a gain of 335 quality-adjusted life-years and a saving of EUR50,334,756 for the society. Had cALND been omitted in all eligible patients, the total gain would have been more than double. The implementation of the Z0011 recommendations resulted in substantial savings and health gain in Germany. Our findings suggest that it is beneficial to introduce additional policy measures to promote further uptake of the Z0011 recommendations in clinical practice.

The Value of Fine Needle Aspiration Biopsy in the Pre-Operative Assessment of the Axilla in Breast Cancer Patients

This paper reviews the role of fine needle aspiration biopsy (FNAB) in assessing the axilla prior to definitive surgery or neoadjuvant therapy in breast cancer patients. The radiological criteria for biopsy are discussed and pathological techniques and pitfalls illustrated. The sensitivity and specificity of the technique and the clinical utility are addressed, with particular reference to the current controversies in the management of the axilla in the light of the American College of Surgeons Oncology Group Z0011 trial results. The low morbidity procedure of FNAB is recommended when the radiological and clinical features suggest a high yield from the abnormal axillary nodes, with consideration of core biopsy if an expected positive result is not obtained or the circumstances require tissue for ancillary studies. In conclusion, FNAB of the axilla is a highly sensitive procedure which can offer further valuable information to assist in clinical decision making. The technique is of particular value in the setting of a large primary tumour size and multiple enlarged nodes. A summary flow chart is provided to facilitate pre-operative management of the axilla and to encourage a universal approach.

242P Patterns of management of positive sentinel lymph nodes in breast cancer patients after the American College of Surgeons Oncology Group Z0011 trial: A retrospective cohort

The management of axillary lymph nodes in breast cancer patients has changed over the past years. The ACOSOG-Z0011 clinical trial introduced drastic changes to the traditional surgical practice for early breast cancer with positive sentinel lymph nodes (SLNs). This study evaluates how these changes have affected the surgical management of early breast cancer at our institution.

Axillary Needle Biopsy in the Era of American College of Surgeons Oncology Group (ACOSOG) Z0011: Institutional Experience With a Largely Urban Minority Population and Review of the Literature

Background: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that sentinel lymph node biopsy (SLNB) alone is adequate for axillary control in patients with one to two positive axillary lymph nodes. However, axillary lymph node dissection (ALND) is required in patients with N1 disease diagnosed with a preoperative needle biopsy. In this report, we determined how many patients could potentially have had SNB alone based on finding only one to two positive nodes in the axilla.Methods: A retrospective review of patients with positive preoperative axillary needle biopsy undergoing ALND was used to identify rates of high volume axillary disease (>2 positive nodes). Wilcoxon’s rank-sum and Fisher’s exact test were used for statistical analysis. A review of the literature is included for comparison.Results: 73% of 51 total patients with a positive needle biopsy had >2 positive nodes on axillary dissection. The high-volume axillary disease was significantly more likely with the presence of lymphovascular invasion and extranodal extension.Conclusions: Patients with positive preoperative axillary needle biopsies have a significantly higher rate of high volume axillary disease. However, at least one-quarter of these patients will have <3 positive nodes and potentially could have been treated with SNB alone.

Imaging Evaluation of the Axilla-A National Survey of Clinical Practice Among Radiologists.

To assess awareness and implementation of the American College of Surgeons Oncology Group Z0011 trial findings, approaches to axillary nodal imaging, and to identify differences in practice based on respondent characteristics. An online survey was distributed to members of the Society of Breast Imaging. Questions regarded demographics, evaluation approaches, and impact of the Z0011 trial. Poisson regression with robust standard errors to regression was used to generate multivariable-adjusted relative risks and 95% confidence intervals (CIs) for associations. The response rate was 21.7% (430/2007). The majority (295/430, 68.6%) reported always performing axillary US in patients with a BI-RADS 4B, 4C, or 5 breast mass. Most respondents (299/430, 69.5%) were familiar with the findings of the Z0011 trial. Radiologists in academic practice were 0.67 (95% CI: 0.54-0.83) times less likely than private practice radiologists to perform axillary US in all masses and 1.31 (95% CI: 1.13-1.52) times more likely to be very familiar with the trial. Frequency of axillary US showed no association with time spent in breast imaging, years in practice, or presence of dedicated breast surgeons. Increased time in breast imaging and presence of dedicated breast surgeons was strongly associated with familiarity with the trial. No association was observed with years in practice. Most respondents (291/430, 67.7%) made little or no change to their practice based on trial findings. There is wide variability in approaches to axillary nodal evaluation, demonstrating a need for improved education and guidelines for axillary imaging in breast cancer patients.

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.

Added Value of MRI for Invasive Breast Cancer including the Entire Axilla for Evaluation of High-Level or Advanced Axillary Lymph Node Metastasis in the Post–ACOSOG Z0011 Trial Era

Background In the post-American College of Surgeons Oncology Group Z0011 trial era, radiologists have increasingly focused on excluding high-level or advanced axillary lymph node metastasis (ALNM) by using an additional MRI scan positioned higher than lower axillae; however, the value of these additional scans remains undetermined. Purpose To evaluate whether a standard MRI protocol is sufficient to exclude high-level or advanced ALNM in breast cancer or additional MRI of entire axilla is needed. Materials and Methods This retrospective study evaluated women with invasive breast cancer who underwent breast MRI from April 2015 to December 2016. Some underwent neoadjuvant chemotherapy (NAC) and others underwent upfront surgery. Standard (routine axial scans including the lower axillae) and combined (routine axial scans plus additional scans including the entire axilla) MRI protocols were compared for high-level or advanced ALNM detection. Clinical-pathologic characteristics were analyzed. Uni- and multivariable logistic regression was performed to identify predictors of high-level or advanced ALNM. Results A total of 435 women (mean age ± standard deviation, 52 years ± 11) were evaluated (65 in the NAC group, 370 in the non-NAC group). With the standard MRI protocol, predictors of high-level ALNM were peritumoral edema (odds ratio [OR], 12.3; 95% CI: 3.9, 39.4; P < .001) and positive axilla (OR, 5.9; 95% CI: 2.0, 15.2; P < .001). Only three of 289 women with negative axillae without peritumoral edema had high-level ALNM. Predictors of advanced ALNM were positive axillae (OR, 8.9; 95% CI: 3.7, 21.5; P < .001) and peritumoral edema (OR, 2.8; 95% CI: 1.1, 6.9; P = .03). Only six of 310 women who had negative axillae without peritumoral edema had advanced ALNM. Conclusion The performance of standard MRI was satisfactory in excluding high-level and advanced axillary lymph node metastasis in most patients with breast cancer. However, the presence of peritumoral edema or positive axillae in the MRI findings emphasizes the benefits of a combined MRI protocol. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Abe in this issue.

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.

Impact of Axillary Dissection Among Patients With Sentinel Node-Positive Breast Cancer Undergoing Mastectomy.

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.

Extranodal Tumor Deposits in the Axillary Fat Indicate the Need for Axillary Dissection Among T1-T2cN0 Patients with Positive Sentinel Nodes.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated the safety of omitting axillary lymph node dissection (ALND) in T1-T2cN0 patients with fewer than three positive sentinel nodes (SLNs) undergoing breast-conservation therapy. While microscopic extracapsular extension (mECE) > 2mm is associated with increased nodal burden, the significance of extranodal tumor deposits (ETDs) in the axillary fat is uncertain. Consecutive patients with T1-T2cN0 breast cancer undergoing sentinel node biopsy and ALND for SLN metastases from January 2010 to December 2018 were identified. ETDs were defined as intravascular tumor emboli or metastatic deposits in the axillary fat. Clinicopathologic characteristics and nodal burden were compared by ETD status. Among 1114 patients, 113 (10%) had ETDs: 81 (72%) were intravascular tumor emboli and 32 (28%) were soft tissue deposits. Patients with ETDs had larger tumors (median 2.2 vs. 2.1cm; p = 0.033) and more often had mECE (83% vs. 44%; p < 0.001). On univariable analysis, presence of ETDs (odds ratio [OR] 9.66, 95% confidence interval [CI] 6.36-14.68), larger tumors (OR 1.47, 95% CI 1.25-1.72), and mECE (OR 10.73, 95% CI 6.86-16.78) were associated with four or more additional positive non-SLNs (NSLNs; all p < 0.001). On multivariable analysis, ETDs remained associated with four or more positive NSLNs (OR 5.67, 95% CI 3.53-9.08; p < 0.001). ETDs were strongly associated with four or more positive NSLNs (OR 7.15, 95% CI 4.04-12.67) among patients with one to two positive SLNs (n = 925). Among T1-T2cN0 patients with SLN metastases, ETDs are strongly associated with four or more positive NSLNs at ALND. Even among those who may otherwise meet the criteria for omission of ALND, the presence of ETDs in axillary fat warrants consideration of ALND.

Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving Surgery: Results from a Quality Assurance Process Integrated into the INSEMA Trial

After publication of the radiation field design in the American College of Surgeons Oncology Group Z0011 trial, a radiation therapy quality assurance review was integrated into the Intergroup-Sentinel-Mamma (INSEMA) trial. We aimed to investigate the role of patient characteristics, extent of axillary surgery, and radiation techniques for dose distribution in ipsilateral axillary levels. INSEMA (NCT02466737) has randomized 5542 patients who underwent breast-conserving surgery. Of these, 276 patients from 108 radiation therapy facilities were included in the central review, using the planning records of the first 3 patients treated at each site. Of the 276 patients, 41 had major deviations (ie, no axillary contouring or submission of insufficient records) leading to exclusion. A total of 235 (85.1%) radiation therapy planning records were delineated according to the INSEMA protocol, including 9 (3.8%) cases with minor deviations. At least 25% of INSEMA patients were unintentionally treated with ≥95% of the prescribed breast radiation dose in axillary level I. Approximately 50% of patients were irradiated with a median radiation dose of more than 85% of prescription dose in level I. Irradiated volumes and applied doses were significantly lower in levels II and III compared with level I. However, 25% of patients still received a median radiation dose of ≥75% of prescription dose to level II. Subgroup analysis revealed a significant association between incidental radiation dose in the axilla and obesity. Younger age, boost application, and fractionation schedule showed no impact on axillary dose distribution. Assuming ≥80% of prescribed breast dose as the optimal dose for curative radiation of low-volume disease in axillary lymph nodes, at least 50% of reviewed INSEMA patients received an adequate dose in level I, even with contemporary 3-dimensional techniques. Dose coverage was much less in axillary levels II and III, and far below therapeutically relevant doses.

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.

Lobular Histology Does Not Predict the Need for Axillary Dissection Among ACOSOG Z0011-Eligible Breast Cancers.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned. From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients. Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p < 0.001). ILC more often had SLN macrometastases (81.7% ILC vs. 69.4% IDC; p = 0.01) and more than 2mm of ECE (30.8% ILC vs. 19.5% IDC; p = 0.03), but the proportions of cases with three or more positive SLNs were similar in the two groups (14.4% ILC vs. 9.9% IDC; p = 0.2). The ALND procedure was performed for 20 ILC patients (19.2%) compared with 97 IDC patients (13.7%) (p = 0.2). Additional positive nodes were found in 80% of the ILC patients versus 56.7% of the IDC patients (p = 0.09). The ALND and nodal burden rates were similar in the estrogen receptor-positive (ER+) subset analysis. In the multivariable analysis, lobular histology (p = 0.03) and larger tumors (p = 0.03) were associated with additional positive nodes. During a median follow-up period of 42months, there were no isolated axillary recurrences. Despite a higher proportion of SLN macrometastases and association with more positive nodes at ALND, lobular histology does not predict the need for ALND. ALND is not indicated on the basis of histology among patients otherwise meeting Z0011 criteria.

THE ROLE OF INTRAOPERATIVE FROZEN SECTION OF SENTINEL LYMPH NODES IN UPFRONT BREAST CONSERVATION CANCER SURGERY

Objective: Sentinel lymph node biopsy is the standard of care in clinically negative axilla in breast cancer patients for which frozen section (FS) is routinely performed intraoperatively. The objective of this study was to justify the use of FS in terms of number of tests performed and their impact on decision-making and cost saving. Materials and Methods: We retrospectively reviewed our prospectively maintained data from January 2014 to January 2018 for intraoperative FS in upfront breast conservation surgery patients. Results: A total of 357 patients were studied. All were female. Median age was 50 years (24–84). Mean tumour size was 29.11 mm. Numbers of sentinel lymph nodes identified were 1 in 50 (14.2%) patients, 2 in 121 (33.89%) patients and ≥3 in 186 (52%) patients. Number of positive sentinel lymph nodes was 0 in 264 (73.9%) patients, 1 in 62 (17.4%) patients, 2 in 20 (5.6%) patients and ≥3 in 11 (3.08%) patients. Axillary lymph node dissection (ALND) was offered to 30 (8.4%) patients as per the American College of Surgeons Oncology Group Z0011. The results for ALND showed that only 8 (2.3%) out of 30 patients had positive nodes identified in the additional axillary nodes dissected. Sensitivity of FS was 97% and specificity was 98.86%. False-negative rate was 3.22%. Conclusion: Intraoperative FS can be safely omitted in early breast cancer patients undergoing upfront breast conservation cancer surgery due to high sensitivity and specificity leading to low false-negative rates. ALND can be performed as a second operation as warranted only in a minority of patients. Key words: American College of Surgeons Oncology Group Z0011 trial, axillary lymph node dissection, intraoperative frozen section, sentinel lymph node biopsy

Evaluation of axillary lymph node metastasis burden by preoperative ultrasound in early-stage breast cancer with needle biopsy-proven metastasis.

The findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial have questioned the use of axillary lymph node (ALN) dissection (ALND) in breast cancer patients with low ALN burden. In this study, our aim was to evaluate axillary nodal metastasis burden in patients with early-stage breast cancer who presented with metastatic lymph nodes diagnosed by fine needle aspiration biopsy (FNAB). The data from 346 patients with cT1-T2 breast cancer who showed positive FNAB results and were seen at Tianjin Medical University Cancer Hospital from January 2014 to December 2017 were retrospectively analyzed. The patients were divided into high axillary nodal burden (≥ 3 positive lymph nodes) or low axillary nodal burden (one to two positive lymph nodes) groups. The clinical, radiological, and pathological features were compared between the two groups. From the 346 patients, 136 (39.3%) had low axillary nodal burden and 210 patients had high axillary nodal burden. Compared to patients with high metastatic burden, the patients with low metastatic burden were more likely to have two or fewer abnormal lymph nodes detected by AUS (95.6% vs. 65.3%, p < 0.05), and more likely to have HR-/HER2- lesions (15.4% vs. 5.2%, p < 0.05). Multivariate analysis revealed that patients with more than two abnormal lymph nodes had an odds ratio of 18.385 (95% CI 7.315-46.205, p < 0.05) to have axillary metastasis. The presence of three or more abnormal lymph nodes on AUS was a significant indicator of high axillary nodal burden in early-stage breast cancer patients with positive FNAB findings. The combination of radiological and clinicopathological findings allows physicians to identify patients with high axillary nodal burden who will likely benefit from ALND in the post-ACOSOG Z0011 trial era.

Effect of the American College of Surgeons Oncology Group Z0011 trial on axillary management in breast cancer patients in the Australian setting

The American College of Surgeons Oncology Group Z0011 Trial demonstrated that early breast cancer patients with positive axillary sentinel lymph nodes treated with breast-conserving surgery and breast radiotherapy had no additional oncologic benefit of proceeding to an axillary lymph node dissection (ALND). The extent to which practice has changed in Australia remains unclear. The aim of this study was to investigate the effect of the Z0011 trial on the management of positive axillary sentinel nodes at an Australian institutional level. We reviewed all breast cancer cases treated at the Sydney Adventist Hospital over a 10-year period from 1 January 2008 to 31 December 2017. Patients who fulfilled the Z0011 trial criteria were selected. These patients were divided into two groups according to the year of surgery, before and after 1 January 2011 when the Z0011 study was published. Clinicopathologic data and axillary surgical management were compared. Of the 237 patients fulfilling the Z0011 trial criteria, there were 73 patients before and 158 patients after 1 January 2011. In the earlier group the rate of proceeding to an ALND following a positive sentinel node was 78.1% compared to 43.7% in the latter group (P<0.0001). There was a significant decline in the rate of ALND over this 10-year period (r=-0.79, P=0.006). The Z0011 trial has influenced the surgical management of the axilla leading to a significant reduction in the rate of an ALND in patients fulfilling the Z0011 trial criteria at our institution.

Abstract P3-03-30: Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy

Abstract Background:American College of Surgeons Oncology Group Z0011 trial showed that axillary lymph node dissection (ALND) had no impact on recurrence and survival in patients with positive sentinel lymph node (SLN) after breast-conserving surgery. However, it is still unknown if the omission of ALND can be applicable to patients treated with mastectomy. The aim of this study wasto evaluate whether ALND could be safely omitted for patients with SLN–positive breast cancer after mastectomy. Methods: From a prospective database of 296 patients with clinically node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy (SLNB) from March 2006 to December 2016, 81 patients who had positive SLNs were selected. Patient characteristics and prognosis were compared between SLN-positive patients with and without ALND. Patients treated with neoadjuvant chemotherapy were excluded from the analysis. Lymphatic mapping was performed using a combined method of blue dye and radioisotope. Results: The median age of entire patients was 57.0 (range: 32-85) years and the median tumor size was 2.5 (range: 0.6-7.9) cm. Of 81 patients, 23 (28.4%) patients omitted ALND. Patients with SLNB alone were more likely to have smaller SLN involvements (p&amp;lt;0.001): micrometastasis was identified in 13 (56.5%) patients in SLNB-alone group and 9 (15.5%) patients in ALND group. The number of positive SLN was comparable between SLNB-alone (median: 1.0, range: 1-6) and ALND groups (median: 1.0, range: 1-5) (p=0.063). There was no significant difference in characteristics including age, tumor size and tumor subtypes between the two groups. Post-mastectomy radiotherapy was performed in 5 (21.7%) patients with SLNB alone and 16 (27.6%) patients with ALND (p=0.588). The majority of patients with macrometastatic SLN received adjuvant chemotherapy in both groups (83.3% vs. 75.5%, p=0.562). Twenty (87.0%) and 51 (87.9%) patients received adjuvant endocrine therapy in SLNB-alone and ALND group, respectively (p=0.584). After a median follow-up of 54.7 months, no axillary recurrence was observed in both groups and 5-year disease-free survival was not significantly different between the two groups (75.0% vs. 88.8%, p=0.489). Lymphedema was observed significantly more often after ALND than after SLNB (22.4% vs. 4.3%, p=0.045). Conclusions: These data suggested that ALND could be safely omitted in SLN-positive breast cancer patients treated with mastectomy and appropriate systemic therapy. Citation Format: Matsumoto A, Umemoto Y, Jinno H. Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-30.

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.