Long-Term Survival Outcomes and Risk Factors for Axillary and Locoregional Recurrence in Japanese Patients with Sentinel Node-Positive Breast Cancer Treated in Accordance with the ACOSOG Z0011 Strategy.

INTRODUCTION: In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown. METHODS: Long-term survival outcomes were investigated by analyzing data from patients enrolled in the feasibility study. Data from the feasibility study patients, and from patients eligible for the Z0011 strategy after its introduction into clinical practice, were subjected to multivariate logistic regression analysis to identify risk factors for axillary and locoregional recurrence. RESULTS: Regarding long-term outcomes for the feasibility study patients (n = 189), distant disease-free survival rates at 5 and 7 years were 90.4 ± 2.1% and 85.9 ± 2.6%, respectively, and overall survival rates at 5 and 7 years were 97.3 ± 1.2% and 95.3 ± 1.7%, respectively. Analysis of data from these patients plus the 93 who received Z0011 in clinical practice (total, n = 282) identified the following independent risk factors for axillary recurrence: absence of high axillary tangential irradiation (OR, 5.87 [95% CI, 1.09-31.35], p = 0.04) and number of positive sentinel lymph nodes (OR, 4.65 [95% CI, 1.11-19.48], p = 0.04). Only high Ki67 labeling index (OR, 5.92 [95% CI, 1.31-26.70], p = 0.02) was identified as an independent risk factor for locoregional recurrence. CONCLUSION: Long-term survival outcome results of the feasibility study show that the Z0011 strategy can be used to treat Japanese patients with early-stage breast cancer. Our findings regarding risk factors suggest that high axillary tangent irradiation is necessary for the prevention of axillary recurrence and that irradiation, including of the regional lymph nodes, should be considered, especially in patients with high Ki67 index values.

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

BACKGROUND: 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. METHODS: Patients ≥ 18 years 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). RESULTS: 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). CONCLUSIONS: 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.

Recent Advances in the Upfront Surgical Management of the Axilla in Patients with Breast Cancer.

Nodal status is an important prognostic indicator. Upfront axillary surgery for patients with breast cancer has historically been both diagnostic and therapeutic-serving to determine nodal status and inform adjuvant therapies, and to remove clinically significant disease. However, trials of de-escalation or omission of axillary surgery altogether consistently demonstrate noninferior oncologic outcomes in a wide variety of patient subsets. These strategies also reduce the morbidity associated with either sentinel lymphadenectomy or axillary lymph node dissection. Here we will briefly review landmark trials that have shaped upfront axillary surgery as well as recent advances, and discuss areas of ongoing investigation and future needs.

Omission of axillary lymph node dissection for breast cancer patients with three or more positive sentinel lymph nodes.

PURPOSE: The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs. METHODS: Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer). RESULTS: We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22). CONCLUSION: Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.

Could axillary lymph node dissection be omitted in the mastectomy patient with tumor positive sentinel node?

Background: Recent data from the ACOSOG Z0011 trial suggest that axillary lymph node dissection (ALND) may not be necessary for patients with positive sentinel lymph node biopsy (SLNB) receiving breast-conserving surgery (BCS) with irradiation. However, consensus statements and guidelines have recommended that patients undergoing mastectomy with tumor-positive sentinel node undergo completion ALND. In this study, we compared the locoregional recurrence rate of patients with tumor-positive sentinel nodes among three groups: mastectomy with SLNB, mastectomy with ALND and BCS with SLNB. Method: We identified 6,163 women with invasive breast cancer who underwent surgical resection at our institution between January 2000 and December 2011. Clinicopathologic data obtained from the prospectively collected medical database were analyzed retrospectively. Among the patients with sentinel node positive, mastectomy with SLNB was performed in 39 cases, mastectomy with ALND in 181 cases, and BCS with SLNB in 165 cases. The primary end point was the loco-regional recurrence rate. Results: Clinicopathologic characteristics were similar among the groups. There were no cases of loco-regional recurrence in the sentinel groups. At a median follow-up of 61.0 months (last follow-up May 2013), the loco-regional recurrence rate of each group was 0% for BCS with SLNB and mastectomy with SLNB only, and 1.7% for mastectomy with ALND (p=0.182). Conclusion: In our study, there was no significant difference in loco-regional recurrence rates between groups. This result lends weight to the argument that SLNB without ALND may be a reasonable management for selected patients with appropriate surgery and adjuvant systemic therapy.

Is Routine Intraoperative Frozen Section Analysis of Sentinel Lymph Nodes Necessary in Every Early-Stage Breast Cancer?

Purpose: Clinical application of the ACOSOG Z0011 trial results allows clinically node-negative breast cancer patients who meet criteria to avoid axillary dissection even when 1-2 sentinel lymph nodes (SLNs) are positive for metastatic disease. Intraoperative frozen section (iFS) analyses of SLNs were thought to reduce re-operation rates despite variable reported sensitivity and possibility of a false negative result. This study evaluated the rate of re-operations prevented by SLN iFS in a tertiary care hospital in Bangkok, Thailand, over a 6-year time-frame. Patients and Methods: From April 2016 to April 2022, 1284 sentinel lymph node biopsy (SLNB) procedures were performed. Of these, 214 cases were breast-conserving surgery in accordance with the ACOSOG criteria with concomitant usage of iFS. Clinicopathological features of these cases were collected and analyzed. Re-operation rates prevented by the additional intervention were reported. Results: Only five additional operations were prevented with the usage of 214 iFS. The discordance rate between frozen and permanent sections in terms of presence of metastatic disease and number of total lymph nodes was around 15%. Tumor staging, node staging, Nottingham histologic grading and lymphovascular invasion are significant predictors of SLN metastasis. Conclusion: iFS results in a very low prevention rate for follow-up ALND in patients with preoperative clinically negative axillary nodes and is associated with a non-negligible discordance rate with permanent sections. Our study suggests iFS may be avoided in most cases of early-stage clinically and radiographically node-negative breast cancer patients. Doing so may reduce surgical costs and total operative time without a significant impact on the overall quality of treatment and standard of care.

Axilla lymph node dissection can be safely omitted in patients with 1-2 positive sentinel nodes receiving mastectomy: a large multi-institutional study and a systemic meta-analysis.

PURPOSE: This study aimed to evaluate whether axillary lymph node dissection (ALND) can be omitted in patients with 1-2 positive sentinel lymph nodes (SLNs) who received total mastectomy (TM). METHODS: Consecutive breast cancer patients with 1-2 positive SLNs were retrospectively reviewed from a multi-institutional database. Patients were divided into sentinel lymph node biopsy (SLNB) group and ALND group. Administration of adjuvant chemotherapy and survival were compared between groups. To further verify the results, a meta-analysis was also conducted. RESULTS: Among the 1161 enrolled patients, 893 (76.9%) received ALND and 268 (23.1%) underwent SLNB alone. Administration of chemotherapy was comparable between the two groups (91.1% vs. 90.6%, P = 0.798), which was consistent in TM (P = 0.638) and BCS cohort (P = 0.576). After a median follow-up of 36 months, no significant difference was observed between the two groups in recurrence-free survival (P = 0.583) regardless of surgery of breast. During further meta-analysis, 13 out of 4733 relative studies reported the association of axillary surgery and disease-free survival (DFS) or overall survival (OS) in 1-2 positive SLNs patients. Pooled analysis showed no difference in adjusted DFS (HR 0.84, 95% CI 0.70-1.02) or OS (HR 1.02, 95% CI 0.93-1.11) between SLNB and ALND groups. Survival benefit of ALND remained non-significant after restricting the analysis in four studies with patients only receiving BCS, or in three studies with patients only receiving TM. CONCLUSION: Further ALND does not impact adjuvant chemotherapy administration or disease outcome in breast cancer patients with 1-2 positive SLNs treated with TM.

Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital.

BACKGROUND: In 2021, there is an increased global trend for sending sentinel lymph node biopsy (SLNB) specimens for permanent section (PS) without intraoperative frozen sections (FS). This pilot study conducted in Thailand determines the re-operation rate for SLNB without FS. METHOD: We retrospectively reviewed 239 SLNB cases without FS at King Chulalongkorn Memorial Hospital from April 2016 to April 2021. The patients were diagnosed with primary invasive breast cancer with clinically negative nodes. The clinical nodal status was assessed from physical examination. The re-operation rate was determined by the number of positive SLNs; where 3 more nodal metastases were subjected to a second surgical procedure. RESULT: Between April 2016 and April 2021, 239 patients who had undergone SLNB in accordance with ACOSOG Z0011 criteria with PS alone was enrolled. A total of 975 SLNs were removed from these 239 patients, with an average of 4.15 nodes per patient. Out of 239 patients, 21 (8.8%) and 6 (2.5%) had metastatic disease in 1 and 2 nodes, respectively. The remaining 212 (88.7%) patients had no nodal metastasis. None of the patients were subjected to a second surgical procedure. CONCLUSION: We conclude that the implementation of SLNB with PS analysis alone in patients who satisfy the ACOSOG Z0011 criteria, with a re-operation rate of 0%, does not have outcomes that would be altered by the standard of care additional FS analysis. With ommision of FS analysis, operation cost, operative time and anesthetic side effects are projected to decrease.

Update on sentinel node pathology in breast cancer.

Pathologic examination of the sentinel lymph nodes (SLNs) in patients with breast cancer has been impacted by the publication of practicing changing trials over the last decade. With evidence from the ACOSOG Z0011 trial to suggest that there is no significant benefit to axillary lymph node dissection (ALND) in early-stage breast cancer patients with up to 2 positive SLNs, the rate of ALND, and in turn, intraoperative evaluation of SLNs has significantly decreased. It is of limited clinical significance to pursue multiple levels and cytokeratin immunohistochemistry to detect occult small metastases, such as isolated tumor cells and micrometastases, in this setting. Patients treated with neoadjuvant therapy, who represent a population with more extensive disease and aggressive tumor biology, were not included in Z0011 and similar trials, and thus, the evidence cannot be extrapolated to them. Recent trials have supported the safety and accuracy of sentinel lymph node biopsy (SLNB) in these patients when clinically node negative at the time of surgery. ALND remains the standard of care for any amount of residual disease in the SLNs and intraoperative evaluation of SLNs is still of value for real time surgical decision making. Given the potential prognostic significance of residual small metastases in treated lymph nodes, as well as the decreased false negative rate with the use of cytokeratin immunohistochemistry (IHC), it may be reasonable to maintain a low threshold for the use of cytokeratin IHC in post-neoadjuvant cases. Further recommendations for patients treated with neoadjuvant therapy await outcomes data from ongoing clinical trials. This review will provide an evidence-based discussion of best practices in SLN evaluation.

Determining the benefit of neoadjuvant chemotherapy in reduction of axillary dissection rates in Z0011 trial cohort with high nodal burden.

Background: In breast cancer patients fulfilling the Z0011 trial criteria, axillary lymph node dissection (ALND) is reserved for patients with a high nodal burden of ≥3 metastatic nodes. In this group of patients, to avoid an ALND, neoadjuvant chemotherapy (NACT) could be given instead to achieve nodal pathological complete response (pCR). However, the benefit of NACT in achieving nodal pCR and avoiding ALND in this group of patients is unknown. We aimed to determine the nodal pCR rate in this group of patients who otherwise would have needed an ALND. Methods: cT1-2N0 breast cancer patients, with histologically proven nodal metastasis, who underwent NACT were identified from a prospectively maintained database. The sonographic criteria of ≥3 abnormal nodes, which has been reported as highly predictive of high nodal burden, was then used to identify the high nodal burden group. Nodal pCR was determined based on the ALND following NACT. Results: Twenty-four patients with high nodal burden were identified. Mean age was 55.2 years. 91.7% had invasive ductal carcinoma and 29.2% had grade III cancer. 54.2% achieved nodal pCR which was associated with ypT (P=0.006). Nodal pCR was 75%, 70% and 30% in the triple negative, human epidermal growth factor receptor2 (HER2) positive and ER/PR+HER2- tumors, respectively. Conclusions: In the postulated T1-2 breast cancer patients with high nodal burden, needing an upfront ALND, NACT could result in nodal pCR of 54.2%, with higher pCR in certain subtypes. Hence, to minimize ALND risk, NACT should be offered in this high nodal burden group.

A multidisciplinary approach to axillary lymph node staging with ultrasound in the setting of a highly suggestive or suspicious breast mass.

The radiologists' role in axillary imaging in the setting of a suspicious breast mass is evolving in light of the Z0011 trial leading to expected practice variation. The purpose of our project was to generate a standardized algorithm guiding the utilization of axillary ultrasound in the setting of a highly suggestive or highly suspicious breast mass (BI-RADS 4C or 5) without a known cancer diagnosis. The algorithm was created with Z0011 practices in mind while reflecting the clinical preferences of our radiology and surgical teams. The four breast surgeons at our academic institution were individually queried regarding their preferred axillary imaging and biopsy approach. The best practices for axillary imaging were then developed in a breast imaging intradepartmental meeting. There was agreement among the surgical group that the presence of suspicious axillary lymph node (s) on ultrasound could be used for treatment planning and patient discussion but would not be used for surgical planning in most cases. They also agreed that an ultrasound-guided core needle biopsy of a suspicious axillary lymph node should be deferred until after surgical consultation. Discussion among our breast radiologists resulted in the consensus that axillary ultrasound in the setting of a BIRADS 4 or 5 mass should be deferred at its initial presentation unless there is palpable lymphadenopathy, suspicious lymph node on mammography, or a tumor is at least stage T3, presumably excluding them from Z0011 criteria. The decision was also made to defer biopsies of suspicious axillary lymph nodes without prior surgical consultation/discussion.

Predictive Factors for Unnecessary Axillary Dissection According to SLN Metastasis in T1, T2 Stage Breast Cancer.

The axillary nodes' status is essential in determining the treatment algorithm according to complete clinical staging. Unnecessary axillary lymph node dissection (ALND) has been prevented after sentinel lymph node biopsy (SLNB) has occurred in current practice. However, approximately half of patients with positive SLNB do not have axillary metastatic lymph nodes. Our study aims to predict unnecessary ALND in patients with SLN metastases by evaluating the patients' clinicopathological data. In total, 221 patients with macrometastasis in SLNB who underwent completion ALND were evaluated retrospectively. Patients were divided into two groups: patients with metastases only in the sentinel lymph node and additional axillary lymph nodes. Univariate and multivariate logistic regression analyses were used to analyze the correlation between SLN metastasis and axillary lymph node metastasis; clinicopathological characteristics, including patient age, menopause status, tumor size and grade, receptor status proliferative marker status, and molecular subtypes of the tumor. In the evaluation of T1-2, cN0 breast cancer patients with SLNB in the form of macrometastasis, only SLNB metastasis was found in 118 (53.4%) patients. In 103 (46.6%) patients, additional axillary node metastasis was observed. The risk of additional nodal spread correlated with patient age older than fertility age (age of 49) (p = 0.015, OR: 1.96, 95% CI: 1.14-3.39) and the number of increased metastatic sentinel nodes (p < 0.001). In line with the data shown by our study, the rate of axillary metastases increases in patients over the age of fertility and as the number of metastatic SLNs increases.

Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort.

PURPOSE: In the ACOSOG Z0011 trial, patients with primary breast cancer and 1-2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. METHODS: Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-François Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. RESULTS: Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR)=6.1; 95% confidence interval (CI): 1.4-26.7; P=0.02)) and only one SLN removed (OR=9.1; 95%CI: 2.2-33.3; P=0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR=5.1; 95%CI: 1.2-22.2; P=0.03) was associated with the failure to perform completion ALND when recommended. CONCLUSION: Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients.

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p = 0.002) and high Ki-67 labeling index value (p = 0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42-11.0]; p = 0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.

Can We Avoid Axillary Lymph Node Dissection (ALND) in Patients with 1-2 Positive Sentinel/Low Axillary Lymph Nodes (SLN/LAS+) in the Indian Setting?

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Staging of the Axilla in Breast Cancer and the Evolving Role of Axillary Ultrasound.

Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically. As a result, staging of the axilla has always played a central role in the treatment of breast cancer. Anatomic staging was believed to be important for two reasons: 1) it predicts prognosis and guides medical therapy, and 2) it is a potential therapy for removal of disease in the axilla. This paradigm has now been called into question. Prognostic information is driven increasingly by tumor biology, and trials such as the ACOSOG Z0011 demonstrates removal of axillary disease is not therapeutic. Staging of the axilla has undergone a dramatic de-escalation; however, sentinel lymph node biopsy (SLNB) is still an invasive surgery and represents a large economic burden on the healthcare system. In this review, we outline the changing paradigms of axillary staging in breast cancer from emphasis on anatomic staging to tumor biology, and the evolving role of axillary ultrasound, bringing patients less invasive and more personalized therapy.

Application of the ACOSOG Z0011 criteria to Chinese patients with breast cancer: a prospective study.

BACKGROUND: Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients. METHODS: Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People's Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed. RESULTS: One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26-82] years vs 54 [25-90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred. CONCLUSION: Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China. TRIAL REGISTRATION: ClinicalTrials.gov. Registration number NCT03606616 . Retrospectively registered on 31 July 2018.

Extrapolation of ACOSOG Z0011 trial results-A survey of breast cancer providers.

We surveyed breast providers from a national oncology cooperative group to evaluate axillary management recommendations for patients with 1-2 positive sentinel lymph nodes (+SLNs) with scenarios not explicitly included in the Z0011 trial. These scenarios included patients underrepresented (premenopausal, HER2+/triple-negative tumors, and invasive lobular carcinoma) or excluded (treated with mastectomy or neo-adjuvant chemotherapy [NAC]) from the ACOSOG Z0011 trial. Survey response rate was 94/149 (64%). For patients in underrepresented groups, 45-63% of providers recommended no further axillary treatment. For mastectomy patients, 45-55% recommended multi-disciplinary discussion. 83% felt more data are needed to change practice, but 41% believed there would be significant accrual challenges to a clinical trial. For patients treated with NAC, recommendations varied widely. 85% felt more data are needed to change practice, but 26% felt there would be significant accrual challenges. For all scenarios, 86-100% of radiation oncologists recommended axillary radiation, while surgeons more often recommended no further axillary treatment. Traditional randomized trials are likely not feasible to provide answers to these critical management questions, so more pragmatic or big data studies may be needed.

Changes in utilization of axillary dissection in women with invasive breast cancer and sentinel node metastasis after the ACOSOG Z0011 trial.

The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial demonstrated no survival advantage for women with clinical T1-T2 invasive breast cancer with 1-2 positive sentinel lymph nodes (SLN) who received whole-breast radiation, and no further axillary surgery when compared to women who did undergo axillary lymph node dissection (ALND). We used the National Cancer Database (NCDB) to study changes in utilization of ALND after the publication of this trial. NCDB was queried for female patients from 2012 to 2015 who met Z0011 criteria. Patients were divided into four groups based on Commission on Cancer facility accreditation. Outcome measures include the rate of ALND (nonadherence to Z0011) and the average number of nodes retrieved with ALND. 27,635 patients were identified, with no significant differences in T stage and receptor profiles between groups. Overall rate of ALND decreased from 34.0% in 2012 to 22.7% in 2015. Nonadherence was lowest in Academic Programs (decreasing from 30.1% in 2012 to 20.5% in 2015) and was highest in Community Cancer Programs (41.2% in 2012 to 29.1% in 2015). Median number of positive SLN did not differ between groups (p = .563). Median number of nodes retrieved on ALND decreased from 9 (IQR 5-14) in 2012 to 7 (IQR 4-12) in 2015 (p < .001). In patients who met the ACOSOG Z11 trial guidelines, rates of ALND have decreased over time. However, rates of nonadherence to Z0011 are significantly higher in Community Cancer Programs compared to Academic Programs.

Sentinel lymph node biopsy after introducing Twirl® breast markers into suspicious lymph nodes in breast cancer patients.

Ten stage I/II breast cancer patients with one or two suspicious lymph nodes (LNs) detected on ultrasonography underwent sentinel LN biopsy (SLNB) after the introduction of Twirl® breast markers into each suspicious LN revealed that each Twirl®-marked LN was SLN and was likely the first SLN. Three patients had less than three SLN metastases and were candidates for sparing completion axillary lymph node dissection (cALND). Indeed, of them, one underwent breast-conserving surgery without cALND and the other two underwent total mastectomy with cALND. These results suggest that, as all suspicious LNs are SLNs, patients can be treated with SLNB alone if they fulfill the ACOSOG Z-0011 criteria, despite suspicious LNs yielding positive results on preoperative fine-needle aspiration cytology.