ATNEC: A multicenter, randomized trial investigating whether axillary treatment can be avoided in patients with T1-3N1M0 breast cancer with no residual cancer in the lymph glands after neoadjuvant chemotherapy.

Abstract

TPS615 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40-70% of patients. This raises questions about the benefit of further axillary treatment in patients with no evidence of residual nodal disease (ypN0) post NACT. Methods: Design: ATNEC is a phase 3, randomized (1:1), multi-center UK trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to benign (ypN0), ATNEC randomly assigns patients to axillary treatment (nodal radiotherapy [ART] or axillary nodal clearance [ALND]) vs no further axillary treatment. Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative).Inclusion criteria: Age ≥ 18; Male or female; T1-3N1M0 breast cancer at diagnosis (pre-NACT); FNA or core biopsy confirmed axillary nodal metastases at presentation; ER and HER2 status evaluated on primary tumor; Received standard NACT as per local guidelines; Imaging of the axilla to assess response to NACT;Dual tracer SNB post-NACT and at least 3 nodes removed (sentinel nodes and marked node): If a single tracer is used, the patient is eligible if the involved node is marked pre-NACT and at least 3 nodes removed (including the marked node), If axillary node sampling is performed following failed localization of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node), If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node and at least 3 nodes removed; No evidence of nodal metastases post NACT (ypN0). Exclusion criteria: Bilateral invasive breast cancer; SNB prior to NACT; Previous ipsilateral axillary nodal surgery; Previous cancer within last 5 years or concomitant malignancy. Aims: To assess whether omitting further axillary treatment (ALND & ART) for patients with early-stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease-free survival, and reduces lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomization, avoid bias from exclusions and preserve statistical power. Radiotherapy Quality Assurance: Study has in-built radiotherapy QA program that will be coordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1,900 Status: Recruiting. As of 11-Feb-2022, 39 sites open, 87 patients enrolled, 31 randomized. Clinical trial information: NCT04109079.

Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer: a 1-year longitudinal cohort study

“…This has the potential to motivate patients to complete PROMs, which may result in more HRQoL data for future research. Furthermore, this study provides a foundation for further research on the impact of axillary treatment on HRQoL, as axillary treatment is an emerging area of research [ 16 , 56 – 60 ]. Once the oncological safety of less invasive and less extensive axillary treatments has been evaluated and protocols may be adjusted, this study can be used to develop predictive models and decision-making tools for patients.…”

Quality of life after different axillary treatments in women with breast cancer: a longitudinal cohort study

“…In addition, this study offers patients the perspective that the decline in their QoL may stabilize again after six months. Furthermore, this study provides a foundation for further research on the impact of axillary treatment on QoL, as axillary treatment is an emerging area of research [16, [51][52][53]. Once the oncological safety of less invasive and less extensive axillary treatments has been evaluated and protocols may be adjusted, this study can be used to develop predictive models and decision-making tools for patients.…”

The role of irradiation in the management of the axilla in early breast cancer patients

“…Alternatively, the biopsied node can be clipped and retrieved at the time of SLN biopsy – the so-called targeted ALND ( 24 , 25 ). The ongoing NSABP B-51/RTOG 1304 and ATNEC trials will examine the role of RNI in ypN0 patients ( 26 , 27 ). The Dutch RAPCHEM;BOOG 2020-03 registry study is the first prospective evidence for the safety of selective de-escalation of radiation therapy after NACT for biopsy-proven clinically node positive T1-2N1 early breast cancers.…”

“…The NSABP B-51/RTOG 1304 study will examine whether post-mastectomy radiotherapy combined with RNI or addition of RNI to breast RT following breast conserving surgery increases invasive breast cancer recurrence-free interval in cN1 patients converting to ypN0 after NACT ( 26 ). The ATNEC trial will randomize ypN0 patients to either observation only following SLN biopsy or further axillary treatment (completion ALND or axillary RT) ( 27 ). Other de-escalation studies include the ALLIANCE A011202 trial that will determine whether axillary RT combined with RNI is non-inferior to completion ALND and RNI for higher risk patients with residual nodal macro metastases after NACT followed by SLN biopsy ( 29 ).…”