Breast Cancer Cancer Breast Cancer
Conditions
Interventions
STUDY DESIGN & JUSTIFICATION
The SMALL trial is a prospective, randomised, two-arm, multicentre trial. The recruitment target is 800 patients. It is anticipated that 70 U.K. sites will be opened to re
Sponsors
University of Birmingham
Eligibility
Sex/Gender
Female
Age
47 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 24/06/2025: 1. Female aged =47 years old with screen-detected breast cancer 2. =15 mm maximum tumour diameter on mammogram and ultrasound 3. No associated malignant microcalcification outwith the mass lesion (calcification within the lesion is permitted) 4. Unifocal disease 5. Grade 1 disease on diagnostic core biopsy 6. ER strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei) 7. PR strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei) 8. HER2 negative (0 or 1+ by immunohistochemistry, or 2+ and negative by in situ hybridisation techniques (FISH or DISH) 9. Normal axillary ultrasound axillary, or equivocal ultrasound with benign fine needle aspiration cytology (FNAC) or core biopsy (CB) 10. Must be a technically appropriate candidate for VAE as determined by local MDT 11. Willing to be randomised 12. Able to provide written informed consent 13. Willing and able to undergo standard surgical treatment 14. Willing and able to undergo radiotherapy 15. Willing and able to take standard endocrine therapy 16. No previous diagnosis of ipsilateral breast cancer or DCIS (contralateral DCIS or invasive disease permitted if surgically treated = 5 years previously and disease-free) _____ Previous inclusion criteria as of 02/06/2021: 1. Female aged =47 years old with screen-detected breast cancer 2. =15 mm maximum tumour diameter on mammogram and ultrasound 3. No associated malignant microcalcification outwith the mass lesion (calcification within the lesion is permitted) 4. Unifocal disease 5. Grade 1 disease on diagnostic core biopsy 6. ER strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei) 7. PR strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei) 8. HER2 negative (0 or 1+ by immunohistochemistry, or 2+ and negative by in situ hybridisation techniques (FISH or DISH) 9. Normal axillary ultrasound axillary, or equivocal ultrasound with benign fine needle aspiration cytology (FNAC) or core biopsy (CB) 10. Willing to be randomised 11. Able to provide written informed consent 12. Willing and able to undergo standard surgical treatment 13. Willing and able to undergo radiotherapy 14. Willing and able to take standard endocrine therapy 15. No previous diagnosis of ipsilateral breast cancer or DCIS (contralateral DCIS or invasive disease permitted if surgically treated = 5 years previously and disease-free _____ Previous inclusion criteria: 1. Female aged = 47 years old with screen-detected breast cancer 2. =15mm maximum tumour diameter on mammogram and ultrasound 3. No associated indeterminate, suspicious or malignant mammographic microcalcification associated with the lesion or extending beyond it 4. Unifocal disease 5. Grade 1 disease on diagnostic core biopsy 6. ER strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei) 7. PR strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei) 8. HER2 negative (0 or 1+ by immunohistochemistry, or 2+ and negative by in situ hybridisation techniques (FISH or DISH) 9. Normal axillary ultrasound axillary, or equivocal ultrasound with benign fine needle aspiration cytology (FN
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 24/06/2025: 1. Associated malignant microcalcification outwith the lesion 2. Bilateral breast cancer 3. Pure invasive lobular cancer 4. Grade 2 or grade 3 on core biopsy assessment 5. Not strongly ER or PR positive (Allred score of <7, or equivalent, e.g. <66% positivity of tumour cell nuclei) or HER2 positive tumour 6. Neoadjuvant endocrine therapy (any duration) 7. Unable to provide informed consent 8. Any serious and/or unstable pre-existing medical, psychiatric or other condition that would prevent compliance with the trial or consent process 9. Unfit or unwilling to undergo standard surgical treatment 10. Contra-indications to standard adjuvant therapies (radiotherapy, endocrine therapy) 11. Previous ipsilateral invasive breast cancer or DCIS 12. Other invasive malignancy unless: 12.1. Disease free for 5 years, or 12.2. Previous basal cell carcinoma, cervical carcinoma in-situ, superficial bladder tumour 13. High-risk group for developing breast cancer (as defined by NICE guidance, women undergoing screening more frequently than 3 yearly in the population screening programme) _____ Previous exclusion criteria as of 02/06/2021: 1. Associated malignant microcalcification outwith the lesion 2. Bilateral breast cancer 3. Invasive lobular cancer 4. Grade 2 or grade 3 on core biopsy assessment 5. Not strongly ER or PR positive (Allred score of <7, or equivalent, e.g. <66% positivity of tumour cell nuclei) or HER2 positive tumour 6. Unable to provide informed consent 7. Any serious and/or unstable pre-existing medical, psychiatric or other condition that would prevent compliance with the trial or consent process 8. Unfit or unwilling to undergo standard surgical treatment 9. Contra-indications to standard adjuvant therapies (radiotherapy, endocrine therapy) 10. Previous ipsilateral invasive breast cancer or DCIS 11. Other invasive malignancy unless: - Disease free for 5 years, or -Previous basal cell carcinoma, cervical carcinoma in-situ, superficial bladder tumour 12. High-risk group for developing breast cancer (as defined by NICE guidance) _____ Previous exclusion criteria: 1. Lesions with associated mammographic microcalcification outwith the lesion 2. Bilateral breast cancer 3. Invasive lobular cancer 4. Grade 2 or grade 3 on core biopsy assessment 5. ER or PR negative or HER2 positive tumour 6. Unable to provide informed consent 7. Any serious and/or unstable pre-existing medical, psychiatric or other condition that would prevent compliance with the trial or consent process 8. Unfit or unwilling to undergo standard surgical treatment 9. Contra-indications to standard adjuvant therapies (radiotherapy, endocrine therapy) 10. Previous ipsilateral invasive breast cancer or DCIS 11. Other invasive malignancy treated within the last 5 years 12. High-risk group for developing breast cancer (as defined by NICE guidance)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Re-excision following initial procedure at 3 months following the end of the recruitment period 2. Local recurrence-free survival time for VAE at 3 months after all patients have completed 3 years of annual mammography following randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Complications arising from surgery or VAE at 3 months following the end of the recruitment period 2. Time to ipsilateral breast cancer recurrence at 3 months after all patients have completed 3 years of annual mammography following randomisation 3. Time to development of contralateral invasive breast cancer at 3 months after all patients have completed 3 years of annual mammography following randomisation 4. Overall survival time at 3 months after all patients have completed 3 years of annual mammography following randomisation 5. Quality-adjusted life year (QALY) at 3 months after all patients have completed 3 years of annual mammography following randomisation 6. Quality of life: will be assessed using the following tools: EORTC QLQ-C30 and BR23, EuroQoL EQ-5D, BREAST-Q (breast conserving therapy module). The Quality of Life questionnaires will be completed by patients prior to randomisation at baseline, all other questionnaires will be distributed directly to the patients’ home address by the SMALL Trial office at 6, 12, 24, 36, 48 and 60 months post-randomisation | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed