NBCG

NBCG

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 guidelines.
  • ER positive (usually Allred score ≥3 or H-score ≥10 or >1% of tumour cells stained positive) as determined by the referring site in a laboratory meeting national external quality assurance standards and in accordance with national or ASCO-CAP guidelines (79).
  • HER2 negative (IHC 0-1+, or ISH negative/non-amplified) as determined by the referring site in a laboratory meeting national external quality assurance standards and in accordance with national or ASCO-CAP guidelines (80).  
  • Tumour size and axillary lymph node status; one of the following must apply: 
    1. 4-9 lymph nodes involved AND with any invasive tumour size.
    2. 1-3 nodes involved, at least 1 node containing a macrometastasis (i.e. deposit >2mm diameter) AND with any invasive tumour size.
    3. 1-3 lymph nodes involved with micrometastases only (i.e. deposit >0.2-2mm diameter) AND invasive tumour size ≥ 20mm.
    4. node negative AND invasive tumour size ≥ 30mm.

NOTES: 
a. Nodes containing isolated tumour cell clusters (ITC) only (i.e. deposit ≤0.2mm diameter) will be considered to be uninvolved.
b. Involvement of lymph nodes with macrometastases or micrometastases may be determined either by histological examination or by OSNA or equivalent PCR-based assay.

  • Considered appropriate for adjuvant chemotherapy by the treating physician.
  • 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 up.  
  • Multiple ipsilateral cancers are permitted provided at least one tumour fulfils the tumour size and axillary lymph node entry criteria and none meet any of the exclusion criteria. 
  • Bilateral cancers are permitted provided the tumour(s) in one breast meet the eligibility criteria and the contralateral tumour is ER positive and HER2 negative but not clinically significant, defined by both of the following:
    1. The tumour meets the tumour size and lymph node eligibility criteria, 
      i.e. the following are not acceptable: presence of lymph node macro-metastases; presence of lymph node micrometastases if tumour size >20mm; tumour size >20mm if no lymph node involvement;
    2. The tumour is not considered appropriate for adjuvant chemotherapy by the treating physician. 
  • Short term pre-surgical treatment with endocrine therapy including in combination with non-cytotoxic investigational agents is allowed providing that the duration of treatment does not exceed 8 weeks.
  • Written informed consent for the study.

EXCLUTION CRITERIA

  • ≥10 involved axillary nodes (with either macrometastases and/ or micrometastases) or evidence for internal mammary node involvement.
  • ER negative OR HER2 positive/amplified tumour (as determined by the referring site).
  • Metastatic disease.
    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 only by surgical treatment with or without local radiotherapy AND disease-free for 10 years
    2. basal cell carcinoma of skin or cervical intraepithelial neoplasia 
    3. ductal carcinoma in situ (DCIS) or pleomorphic lobular carcinoma in situ (pleomorphic LCIS) of the breast treated with surgery with or without breast radiotherapy; treatment with anti-oestrogens is not permitted.
  • Use of systemic anti-cancer treatment and/or radiotherapy for breast cancer prior to trial entry* except as follows. 
    1. Short-term pre-surgical endocrine therapy administered as per the inclusion criteria.
    2. Endocrine therapy may be administered following surgery provided this is discontinued at trial entry. 
  • Treatment with agents, including ovarian suppression, known to influence breast cancer growth but prescribed for other indications within one year of trial entry* except as follows.
    1. Use of oestrogen replacement therapy (HRT) provided this is stopped before surgery. 
    2. Drugs administered for in vitro fertilization or fertility preservation.
    3. Use of hormonal contraception.
  • Trial entry* and randomisation more than 12 weeks after completion of breast cancer surgery. Trial entry should ordinarily be within 8 weeks of final surgery.  
  • 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 chemotherapy if given.