OPTIMA

• Female or male, age ≥ 40

• Excised invasive breast cancer with local treatment either completed or planned according to trial guidelines.

• ER positive (>10% of tumour cells stained positive) as determined by the referring site as determined by the referring site in a laboratory meeting national external quality assurance standards, and in accordance with national or ASCO-CAP guidelines.

NOTE: Where ER status is reported by Allred (or Quick) Score or by H-Score, tumours with high scores meet the ER-positive definition but the %staining component of the core is required to determine eligibility for intermediate-score tumours. Refer to the table for mapping.

Eligible Eligibility determined by Ineligible

(ER staining >10%) %staining component of the score (ER staining ≤10%)

Allred (or Quick) Score 6, 7 or 8 4 or 5 3 or less

H-Score >30 10-30 <10

• 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.

• Tumour size and axillary lymph node status; one of the following must apply: 

i. 4-9 lymph nodes involved AND any invasive tumour size.

ii. 1-3 nodes involved, with at least 1 node containing a macrometastasis (i.e. deposit >2mm diameter) AND any invasive tumour size.

iii. 1-3 lymph nodes involved with micrometastases only (i.e. deposit >0.2-2mm diameter) AND invasive tumour size ≥ 20mm.

iv. node negative AND invasive tumour size ≥ 30mm

NOTES: 

a. Lymph 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 PCRbased 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 meets the eligibility criteria and the other, contralateral tumour is not ER negative and/or HER2 positive and not clinically significant, defined by both of the following:

i. The contralateral tumour does not fulfil the tumour size and lymph node eligibility criteria required for trial entry; i.e. the following are not acceptable: 

o presence of lymph node macro-metastases; 

o presence of lymph node micrometastases if the tumour size is ≥20mm; 

o tumour size ≥30mm when there is no lymph node involvement.

ii. The treating physician does not consider that the characteristics of the contralateral tumour alone justify consideration of adjuvant chemotherapy. 

• Short term pre-surgical treatment with endocrine therapy including in combination with noncytotoxic agents is allowed providing that the duration of treatment does not exceed 8 weeks.

• Written informed consent for the study. 

• ≥10 involved axillary nodes (with either macrometastases and/ or micrometastases) or evidence for internal mammary node involvement.

• ER negative OR HER2 positive/amplified (as determined by the referring site).

• Metastatic disease.

• Previous diagnosis of malignancy unless:

i. managed by surgical treatment only and disease-free for 10 years

ii. basal cell carcinoma of skin or cervical intraepithelial neoplasia

iii. ductal carcinoma in situ (DCIS) of the breast treated with surgery only

iv. lobular carcinoma in situ (LCIS) or lobular neoplasia of the breast.

• 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 surgery.

• 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 entry.

• 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 entry.

• Trial entry more than 8 weeks after completion of breast cancer 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. 

Research Nurse: Andra Fielding [andra.fielding@mbht.nhs.uk]

Administrators: research.oncology@mbht.nhs.uk