Breast cancer Cancer Malignant neoplasm of breast
Conditions
Interventions
Control: Chemotherapy followed by endocrine therapy
Experimental: Test directed assignment of chemotherapy or not, followed by endocrine therapy
Follow up length: 10 years
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
40 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria (amended 20/10/2020) and added 14/02/2024: 1. Female or male, age =40 years 2. Excised invasive breast cancer with local treatment either completed or planned according to trial guidelines. 3. ER positive (>10% 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 (83). 4. 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 (84). 5. Tumour size and axillary lymph node status; one of the following must apply: 1.1. 4-9 lymph nodes involved AND any invasive tumour size. 1.2. 1-3 nodes involved, with at least 1 node containing a macrometastasis (i.e. deposit >2mm diameter) AND any invasive tumour size. 1.3. 1-3 lymph nodes involved with micrometastases only (i.e. deposit >0.2-2mm diameter) AND invasive tumour size = 20mm. 1.4. Node negative AND invasive tumour size = 30mm. 2. Considered appropriate for adjuvant chemotherapy by the treating physician. 3. 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. 4. 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. 5. 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. 6. Short term pre-surgical treatment with endocrine therapy including in combination with non-cytotoxic agents is allowed providing that the duration of treatment does not exceed 8 weeks. 7. Informed consent for the study. Previous Inclusion criteria at recruitment start (17/01/2017) added 14/02/2024: Main trial: 1. Female or male, age >= 40 years 2. Excised invasive breast cancer with local treatment either completed or planned according to trial guidelines. 3. 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). 4. HER2 negative (IHC 0-1+, or ISH negative/non-amplified (ratio of HER2/chromosome 17 2mm diameter) AND any invasive tumour size. 5.3. 1-3 lymph nodes involved with micrometastases only (i.e. deposit >0.2-2mm diameter) AND invasive tumour size = 20mm. 5.4 node negative AND invasive tumour size = 30mm.: 6. Considered appropriate for adjuvant chemotherapy by treating physician. 7. 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. 8. Bilateral cancers are permitted provided at least one tumour fulfils the entry criteria and none meet
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria (amended 17/09/2022) and added 14/02/2024: 1. =10 involved axillary lymph nodes (with either macrometastases and/ or micrometastases) or involvement of any of internal mammary, supraclavicular and infraclavicular nodes. 1.1. NOTE: Internal mammary lymph nodes identified by anatomical imaging studies alone will be considered uninvolved where the diameter is =10 involved axillary nodes (with either macrometastases and/ or micrometastases) or evidence for internal mammary node involvement. 2. ER negative OR HER2 positive/amplified (as determined by the referring site). 3. Metastatic disease. 4. Previous diagnosis of malignancy unless: 4.1. managed by surgical treatment only and disease free for 10 years 4.2. basal cell carcinoma of skin or cervical intraepithelial neoplasia or 4.3. ductal carcinoma in situ (DCIS) of the breast treated with surgery only 4.4. lobular carcinoma in situ (LCIS) or lobular neoplasia of the breast. 5. 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. 6. Pre-surgical chemotherapy, endocrine therapy or radiotherapy for breast cancer. Treatment with endocrine agents known to be active in breast cancer including ovarian suppression is permitted provided this was completed >1 year prior to study entry. 7. Commencement of adjuvant treatment prior to trial entry. Short-term endocrine therapy initiated because of, for instance, prolonged
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures amended 30/03/2023 and added 14/02/2024: Main trial: 1. Invasive Breast Cancer Survival (IBCFS) non-inferiority of test-directed chemotherapy treatment and endocrine therapy compared to chemotherapy followed by endocrine treatment 2. Cost-effectiveness evaluation of protocol-specified multi-parameter assay-driven treatment against standard clinical practice Previous primary outcome measures amended 17/01/2023 and added 14/02/2024: Main trial: 1. Invasive disease-free survival (IDFS) non-inferiority of test-directed chemotherapy treatment and endocrine therapy compared to chemotherapy followed by endocrine treatment 2. Cost-effectiveness evaluation of protocol-specified multi-parameter assay-driven treatment against standard clinical practice Previous primary outcome measures: OPTIMA prelim: 1. Identification of a multi-parameter test technology that is suitable for validation in the main study. 2. Recruitment of 300 patients in not more than 2 years from the first centre opening to recruitment, and, for the final 150 patients: 2.1. Patient acceptance rate will be at least 40% 2.2. Recruitment will take no longer than 6 months 2.3. Chemotherapy will start within 6 weeks of signing the OPTIMA consent form for no less than 85% of chemotherapy-assigned patients Main trial: 1. Invasive disease-free survival (IDFS) non-inferiority of test-directed chemotherapy treatment and endocrine therapy compared to chemotherapy followed by endocrine treatment 2. Cost-effectiveness evaluation of protocol-specified multi-parameter assay-driven treatment against standard clinical practice | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures amended 30/03/2023 and added 14/02/2024: 1. Invasive Breast Cancer Free Survival and other outcome measures for patients with low-score tumours for patients with low-score tumours (defined as tumours for which the Prosigna score is below the cut-off [=60] for chemotherapy use) [key secondary endpoint] 2. Recurrence Free Interval (RFI), Invasive Breast Cancer Free Survival (IDFS) and Distant Recurrence Free Interval (DRFI) 3. Breast Cancer Specific Survival (BCSS) and Overall Survival (OS) 4. Health Resource Use and Quality of Life as measured by EQ-5D and FACT-B 5. Patient compliance with long-term endocrine therapy Previous secondary outcome measures amended 17/01/2017 and added 14/02/2024: Main trial 1. Distant recurrence-free survival (DRFS) 2. Breast cancer-specific survival (BCSS) and Overall survival (OS) 3. IDFS for patients with low-risk patients with low-risk tumours (low-risk tumours are tumours for which the Prosigna score is below the cut-off [=60] for chemotherapy use) 4. Health resource use and Quality of life measured by EQ-5D & FACT-B 5. Patient compliance with long-term endocrine therapy Previous secondary outcome measures as of 29/09/2015; the title was amended to include "OPTIMA prelim at recruitment start (05/09/2012)" on 14/02/2024: Main trial: 1. Quality of life and health resource use as measured by EQ-5D & FACT-B 2. Distant disease-free survival 3. Comparative performance of multi-parameter assays (if more than one is adopted) 4. Patient compliance with long-term endocrine therapy 5. Overall survival (OS) | — |
Countries
Australia, England, New Zealand, Norway, Sweden, Thailand, United Kingdom
Contacts
Public ContactGeorgina Dotchin
Outcome results
None listed