POSNOC is a pragmatic, randomised, multicentre, non-inferiority trial.

Aim For women with early stage breast cancer and one or two sentinel node macrometastases, to assess whether adjuvant therapy alone is no worse than adjuvant therapy plus axillary treatment, in terms of axillary recurrence within 5 years.

Stratification: Institution, Age (<50, ≥50), Breast-conserving surgery (BCS) or mastectomy, Estrogen receptor (ER) status (positive, negative), Number of positive nodes (1, 2), Intra-operative sentinel assessment using OSNA (yes, no).

Interventions The study will compare adjuvant therapy alone with adjuvant therapy plus axillary treatment (axillary node clearance (ANC) or axillary radiotherapy (ART)).

Sample Size: 1900 participants

Follow-up: Participants will be followed up for 5 years.

Adjuvant Therapy: All participants will receive adjuvant systemic therapy (chemotherapy and/or endocrine therapy). All participants may receive breast/chest wall radiotherapy. Axillary and supraclavicular fossa radiotherapy is not allowed when randomised to adjuvant therapy alone.

Inclusion Criteria:

• Unifocal or multi-focal invasive tumour with lesion ≤5 cm in its largest dimension, measured pathologically or largest invasive tumour diameter on radiology should be used for women who are randomised intra-operatively or undergo sentinel node biopsy before neoadjuvant therapy (tumour size should be based only on the single largest tumour; do not add the sizes together from the multiple foci)
• At sentinel node biopsy have 1 or 2 nodes with macrometastases (tumour deposit >2.0mm in largest dimension or defined as macrometastasis on molecular assay)
• Fit for axillary treatment and adjuvant therapy
• Have given written informed consent

Exclusion Criteria:

• bilateral invasive breast cancer

• more than 2 nodes with macrometastases

• neoadjuvant therapy for breast cancer except:

  • if sentinel node biopsy performed prior to neoadjuvant chemotherapy in women with early breast cancer
  • short duration of neoadjuvant endocrine therapy is acceptable (up to 3 months)

• previous axillary surgery on the same body side as the scheduled sentinel node biopsy

• not receiving adjuvant systemic therapy

• previous cancer less than 5 years previously or concomitant malignancy except:

  • basal or squamous cell carcinoma of the skin
  • in situ carcinoma of the cervix
  • in situ melanoma
  • contra- or ipsilateral in situ breast cancer