OPTIMA

OPTIMA (EMIT2). Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis. Bruk av Prosigna test til adjuvant behandlingsbeslutning. PI: Bjørn Naume.

INCLUSION CRITERIA

  • Female or male, age ≥ 40
  • Excised invasive breast cancer with local treatment either completed or planned according to trial
  • ER positive (Allred score ≥3 or H-score ≥10 or >1% of tumour cells stained positive) as determined by the referring site (in a laboratory meeting NEQAS standards).
  • HER2 negative (IHC 0-1+, or ISH negative/non-amplified [ratio of HER2/chromosome 17 <2.00 and copy number <6]) as determined by the referring site (in a laboratory meeting NEQAS standards).
  • Axillary lymph node status:
  1. 1-9 lymph  nodes  involved      and   if   1-3   nodes,   at   least   1   node  containing  a macrometastasis (i.e. deposit >2mm diameter)
  2. 1-3 lymph nodes involved with micrometastases only (i.e. deposit >0.2-2mm diameter)

AND tumour size  ≥ 20mm

  • node negative AND tumour size ≥

Note: Nodes containing isolated tumour cell clusters (ITC) only (i.e. deposit ≤0.2mm diameter) will be considered to be uninvolved.

Note: Although it is anticipated that the majority of patients with node positive disease will be identified by histological examination, those diagnosed as macrometastases or micrometastases by OSNA (or equivalent PCR-based assay) are considered eligible. For such patients the eligibility rules i and ii will apply.

  • Considered appropriate for adjuvant chemotherapy by treating
  • Patient must be fit to receive chemotherapy and other trial-specified treatments with no concomitant medical, psychiatric or social problems that might interfere with informed consent, treatment compliance or follow
  • Bilateral cancers are permitted provided at least one tumour fulfils the entry criteria and none meet any of the exclusion

Note: If the patient is regarded as eligible with regard to both cancers, blocks from both lesions will be submitted for Prosigna testing. Clinical management will be based on the higher Prosigna score for patients randomised to test-directed treatment.

  • Multiple ipsilateral cancers are permitted provided at least one tumour fulfils the entry criteria and none meet any of the exclusion

Note: Blocks from more than one lesion should be submitted for Prosigna testing when the lesions are considered to be clinically significant by the referring site and they are interpreted as synchronous primary cancers (based either on the site of the lesions, i.e. in different quadrants, or if they are of differing morphology, i.e. histological type or grade). It is anticipated that laboratories will, as per standard good practice, assess ER and HER2 on the different lesions. Clinical management will be based on the highest Prosigna score for patients randomised to test-directed treatment.

  • Written informed consent for the study

EXCLUSION CRITERIA

  • ≥10 involved axillary nodes (with either macrometastases and/ or micrometastases) or evidence for internal mammary node
  • ER negative OR HER2 positive/amplified (as determined by the referring site).

Note: Patients with non-luminal tumour subtypes identified by Prosigna testing will have central re-testing of receptor status. If they are subsequently identified as having ER negative or HER2 positive/amplified tumours on re-testing they will be treated appropriately for the tumour characteristics and will continue to be followed-up as part of the OPTIMA trial.

  • Metastatic

Note: Formal staging according to local protocol is recommended for patients where there is a clinical suspicion of metastatic disease or for stage III disease (tumour >50mm with any nodal involvement OR any tumour size with 4 or more involved nodes).

  • Previous diagnosis of malignancy unless:
  1. managed by surgical treatment only and disease-free for 10 years
  2. basal cell carcinoma of skin or cervical intraepithelial neoplasia
  • ductal carcinoma in situ (DCIS) of the breast treated with surgery only
  1. lobular carcinoma in situ (LCIS) or lobular neoplasia of the
    • The use of oestrogen replacement therapy (HRT) at the time of surgery. Patients who are taking HRT at the time of diagnosis are eligible provided the HRT is stopped before
    • Pre-surgical chemotherapy, endocrine therapy or radiotherapy for breast cancer. Treatment with endocrine agents known to be active in breast cancer treatment including ovarian suppression is permitted provided this was completed >1 year prior to study
    • Commencement of adjuvant treatment prior to trial entry. Short-term endocrine therapy initiated because of, for instance, prolonged recovery from surgery is permitted but must be discontinued at trial
    • Trial entry more than 8 weeks after completion of breast cancer
    • Planned further surgery for breast cancer, including axillary surgery, to take place after randomisation, except either re-excision or completion mastectomy for close or positive/involved margins which may be undertaken following completion of