POSNOC—POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes

IntroductionACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence.Methods and analysisPOSNOC is a pragmatic, multicentre, non-inferiority, international trial with participants randomised in a 1:1 ratio. Women are eligible if they have T1/T2, unifocal or multifocal invasive breast cancer, and 1 or 2 macrometastases at sentinel node biopsy, with or without extranodal extension. In the intervention group women receive adjuvant therapy alone, in the standard care group they receive ANC or axillary RT. In both groups women receive adjuvant therapy, according to local guidelines. This includes systemic therapy and, if indicated, RT to breast or chest wall. The UK Radiotherapy Trials Quality Assurance Group manages the in-built radiotherapy quality assurance programme. Primary endpoint is 5-year axillary recurrence. Secondary outcomes are arm morbidity assessed by Lymphoedema and Breast Cancer Questionnaire and QuickDASH questionnaires; quality of life and anxiety as assessed with FACT B+4 and State/Trait Anxiety Inventory questionnaires, respectively; other oncological outcomes; economic evaluation using EQ-5D-5L. Target sample size is 1900. Primary analysis is per protocol. Recruitment started on 1 August 2014 and as of 9 June 2021, 1866 participants have been randomised.Ethics and disseminationProtocol was approved by the National Research Ethics Service Committee East Midlands—Nottingham 2 (REC reference: 13/EM/0459). Results will be submitted for publication in peer-reviewed journals.Trial registration numberISRCTN54765244; NCT0240168Cite Now

Can machine learning be used to reduce overtreatment of the axilla in breast cancer? Results from a retrospective cohort study (Preprint)

BACKGROUND Patients with early breast cancer undergoing primary surgery who have low axillary nodal burden can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risk within large patient data sets, but this has not yet been trialled in the arena of axillary node management in breast cancer. OBJECTIVE To assess if machine learning techniques could be used to improve pre-operative identification of patients with low and high axillary metastatic burden. METHODS A single-centre retrospective analysis was performed on patients with breast cancer who had a preoperative axillary ultrasound, and the specificity and sensitivity of AUS were calculated. Machine learning and standard statistical methods were applied to the data to see if, when used preoperatively, they could have improved the accuracy of AUS to better discern between high and low axillary burden. RESULTS The study included 459 patients; 31% (n=142) had a positive AUS, and, among this group, 62% (n=88) had two or fewer macrometastatic nodes at ANC. When applied to the dataset, logistic regression outperformed AUS and machine learning methods with a specificity of 0.950, correctly identifying 66 patients in this group who had been incorrectly classed as having high axillary burden by AUS alone. Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. CONCLUSIONS Machine learning greatly improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than two metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low burden and it is unclear if sentinel node biopsy adds value in this situation. CLINICALTRIAL n/a

TP8.1.1 Does ultrasound quantification of suspicious axillary nodes correlate with pathological results?

Aims Fast-track axillary node clearance (ANC) leads to overtreatment of axilla. Improved quantification by axillary US (AUS) is suggested to avoid unnecessary ANC and proceed with ANC or SLNB based on the number of abnormal axillary nodes. This retrospective study was aimed to evaluate whether ANC can be omitted based on AUS quantification in patients with low axillary burden. Methods Retrospective data of breast cancer patients who underwent ANC following a positive pre-operative axillary nodal biopsy between 1 January 2017 and 31 December 2018 were included in this study. The patients who received neoadjuvant chemotherapy, those having ANC following positive SLNB and those with axillary recurrence were excluded. The histopathology results of ANC were correlated with axillary ultrasound findings. Results 45 patients underwent fast-track ANC following positive axillary core biopsy. On pre-operative AUS, 18 of these patients were reported to have a single abnormal node, while 8 had two abnormal nodes and 19 patients had multiple abnormal nodes. The comparison of the number of metastatic nodes following ANC, and the reported abnormal nodes on pre-operative AUS, showed that 57.3% of patients with 1 – 2 abnormal nodes on AUS had 3 or more metastatic nodes and 26.3% of patients with multiple abnormal nodes on AUS had 1 – 2 metastatic nodes following ANC. Conclusions The quantification of the axillary burden with pre-operative AUS does not correlate with the number of metastatic axillary nodes. The reported relevant axillary burden on AUS is not sufficiently specific to form the basis of omission of ANC.

EP.TH.879Does ‘fast -track’ axillary node clearance following positive core biopsy lead to overtreatment of axilla?

Aims Axillary node clearance (ANC) can cause lifelong disability and conservative axillary dissection is increasingly preferred. However, direct (fast-track) ANC after preoperative axillary biopsy is still performed, which may be overtreating the patients with low axillary burden. This study aims to identify if direct (fast- track) ANC leads to overtreatment of axilla. Methods Retrospective data for all breast cancer patients who underwent surgery between 1 January 2017 and 31 December 2018 were included in this study. The histopathology results of ANC were correlated with axillary ultrasound findings, axillary biopsy or SLNB results and effect of neoadjuvant treatment. These were analysed against the available guidelines to evaluate the current practice. Results 82 patients out of 520 had ANC (15.7%). Four groups were identified. 35.5% of patients diagnosed with nodal infiltration on preoperative biopsy (Group A) had only 1- 2 positive nodes following ANC. Complete pathological response was observed in 37.5% patients with nodal infiltration who had ANC following neoadjuvant chemotherapy (NACT) (Group B). No further nodes were subsequently found in 63.6% of patients who underwent ANC following positive SLNB (Group C). Group D included 2 patients with axillary recurrence. Conclusions 15.7% of breast cancer patients required ANC. The practice of direct (fast-track) ANC after axillary biopsy leads to overtreatment of the axilla, which needs re-evaluation. Targeted axillary dissection could avoid unnecessary axillary dissection in patients with abnormal nodes. This is now recommended in patients who have received NACT but has not been evaluated yet in patients with up front surgery.

EP.TH.930Contemporary trends in the management of micrometastatic axillary disease in the setting of mastectomy – a 5 year single institution experience

Background Since the ACOSOG Z0011 trial, rates of axillary node clearance (ANC) for micrometastatic axillary disease have declined among women undergoing breast conservation surgery (BCS). However, for women undergoing mastectomy, it remains unclear whether omission of ANC is a safe and feasible option. Aims Identify current practice relating to management of the axilla in women with early stage, clinically node negative breast cancer, found to have micrometastatic disease on SNB, who undergo mastectomy Methods From 2013 to 2017 patients with clinical T1-T2Nmi breast cancer undergoing upfront surgery were identified from a prospective institutional database. Receipt of adjuvant radiotherapy or subsequent ANC were assessed. Patients who received neoadjuvant chemotherapy or BCS were excluded. Results 47 patients undergoing mastectomy for ESBC had micrometastasis identified on SNB. The majority of tumours had invasive ductal histology. 16/27 women underwent completion ANC (34%). Six patients had further nodal disease identified in the ANC specimen. 2 had >5 nodes positive. During the study period 31 patients (65%) received adjuvant radiotherapy. Of the patients who did not undergo ANC, 21 (67.7%) received adjuvant radiotherapy. Conclusion At this institution the majority of patients requiring mastectomy with micrometastatic disease on SNB do not undergo subsequent ANC (>60%). Although this is a small patient cohort, these data indicate the rate of residual axillary disease is low, and are in keeping with trends in the literature, and may help inform management decisions in this patient group.

1017 Sentinel Node Biopsy Vs Axillary Node Clearance in Early Breast Cancer

Aim The introduction of sentinel node biopsy (SLNB) in the late 1990s negated the need for axillary node clearance (ANC) in patients demonstrated to have early invasive breast cancer and histologically node-negative disease. However, the latest evidence from large multi-centre randomised trials suggests that patients could be spared this potentially debilitating procedure077. However, these following criteria must be met: Method A retrospective study of the database of breast cancer patients who had ANC between January 2018 to December 2019 in a single institution was undertaken. The histological results of patients who fulfilled the above criteria were analysed. Results Out of 75 patients who had ANC, 2 were excluded due to inadequate data.The average age was 59 (range 34-83).Of the remaining 73 patients, 57 patients (78%) had early breast cancer (T1/2), 11 (19%) of which fulfilled the criteria for sparing of ANC. Of those 11 patients, 8 (73%) had 0 LNs and 3 (27%) had 1 involved lymph node on histological assessment. Conclusions It has been observed that significant morbidity is associated with ANC. A greater subset of patients can benefit from a more sophisticated and evidence-based approach to the management of the axilla in early breast cancer, safely avoiding ANC without compromising survival.

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Background Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.

The NeST (Neoadjuvant Systemic Therapy in Breast Cancer) Study: National Practice Questionnaire of United Kingdom Multi-Disciplinary Decision Making

Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item.Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0% and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT.Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.

Residual lymph node tumour burden following removal of a single axillary sentinel lymph with macrometastatic disease in women with screen-detected invasive breast cancer

Background Women with screen-detected invasive breast cancer who have macrometastatic disease on axillary sentinel lymph node biopsy (SLNB) are usually offered either surgical axillary node clearance (ANC) or axillary radiotherapy. These treatments can lead to significant complications for patients. The aim of this study was to identify a group of patients who may not require completion ANC. Methods Data from the NHS Breast Screening Programme between 1 April 2012 and 31 March 2017 were interrogated to identify women with invasive breast carcinoma and a single sentinel lymph node (SLN) with macrometastatic disease who subsequently proceeded to completion ANC. Univariable and multivariable analyses were performed to identify patients with a single positive SLN who had no further lymph node metastasis on ANC. Results Of the 2401 women included in the cohort, the presence of non-sentinel node disease was significantly affected by: the number of nodes obtained at SLNB (odds ratio (OR) 0.49 for retrieval of more than 1 node), invasive size of tumour (OR 1.63 for size greater than 20 mm), surgical treatment (OR 1.34 for mastectomy), human epidermal growth factor receptor (HER) 2 status (OR 0.71 for HER2 positivity), and patient age (OR 1.10 for age less than 50 years; OR 1.46 for age greater than 70 years). Patients aged less than 70 years, with tumour size smaller than 2 cm, more than one node retrieved on SLNB, and who had breast-conserving surgery had a lower chance of positive non-sentinel nodes on completion ANC compared with other patients. Conclusion This study, of a purely screen-detected breast cancer cohort, identified a subset of patients who may be spared completion ANC in the event of a single axillary SLN with macrometastasis.