SMALL

Overview

The study is a Phase III, randomised, multi-centre trial addressing overtreatment of small screen-detected breast cancer by comparing standard surgery versus minimally invasive vacuum-assisted excision.

In order to be practice changing, it will be necessary to demonstrate that not only is there an acceptable local recurrence risk associated with VAE followed by radiotherapy and endocrine therapy, but also that there is not an excess requirement for additional procedures in the VAE arm, in case of radiologically-determined incomplete excision.

The total number of patients to be recruited is 800; with the 1:2 allocation ratio in favour of vacuum-assisted excision (VAE) (267 standard surgery and sentinel lymph node biopsy, 533 VAE).

70 U.K. sites will be opened to recruitment. All patients will be followed up via the recruiting site for 5 years post-randomisation. Further long-term follow-up data may be collected by the data linkage services.

The final analysis following the initial procedure will be conducted 3 months following the completion of recruitment. This will ensure that all patients have undergone their randomised procedure and been assessed for re-excision. The analysis of complications arising from surgery or VAE will also be conducted at this point. Analysis of the local recurrence free survival and all remaining secondary outcomes will be conducted 3 months after all patients have completed 3 years of annual mammography following randomisation.

Inclusion criteria

• Female aged ≥ 47 years old with screen-detected breast cancer
• ≤15mm maximum tumour diameter on mammogram and ultrasound
• No associated indeterminate, suspicious or malignant mammographic microcalcification associated with the lesion or extending beyond it
• Unifocal disease
• Grade 1 disease on diagnostic core biopsy
• ER strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei)
• PR strongly positive (Allred score of 7 or 8, or equivalent, e.g. at least moderate positivity in >66% of tumour cell nuclei)
• HER2 negative (0 or 1+ by immunohistochemistry, or 2+ and negative by in situ hybridisation techniques (FISH or DISH)
• Normal axillary ultrasound axillary, or equivocal ultrasound with benign fine needle aspiration cytology (FNAC) or core biopsy (CB)
• Willing to be randomised/ Able to provide written informed consent
• Willing and able to undergo standard surgical treatment/ to undergo radiotherapy / to take standard endocrine therapy
• No previous diagnosis of ipsilateral breast cancer or DCIS (contralateral DCIS or invasive disease permitted if surgically treated ≥ 5 years previously and disease-free 

Interventions

Surgery arm:

• Standard surgical treatment as deemed appropriate by local MDT, including axillary sentinel lymph node biopsy
• Adjuvant radiotherapy/endocrine therapy as per local treatment guidelines

VAE arm:

• Image-guided vacuum excision of breast cancer
• No axillary surgery
• Adjuvant radiotherapy to breast
• Adjuvant endocrine therapy

Timeline

Completing recruitment: 31st December 2022

Patient sample size

N=800