Comparative Study

. 2025 Apr 8;15(4):e099702.

doi: 10.1136/bmjopen-2025-099702.

SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Kenneth Elder¹, Charlotte Coles², David Dodwell³, Beatrix Elsberger⁴, Jessica Foster⁵, Claire Gaunt⁵, Julia R Henderson⁶, Iain Lyburn^{7

8

9}, Claire Mabena¹⁰, Jenna Morgan¹¹, Zohal Nabi¹², Sangeetha Paramasivan¹³, Sarah Pinder¹⁴, Sarah Pirrie¹⁵, Shelley Potter^{16

17}, Tracy Roberts¹⁸, Nisha Sharma¹⁹, Elizabeth Southgate¹⁵, Hilary Stobart²⁰, Amruta Talwalkar²¹, Sian Taylor-Phillips²², William Teh²³, Elliot Turner¹⁵, Matthew G Wallis^{24

25}, Dan Rea¹⁵, Stuart McIntosh²⁶

Affiliations

¹ Breast Unit, Western General Hospital, Edinburgh, UK.
² Department of Oncology, University of Cambridge, Cambridge, UK.
³ Population Health, University of Oxford, Oxford, UK.
⁴ Aberdeen Royal Infirmary, Aberdeen, UK.
⁵ Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
⁶ Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool, UK.
⁷ Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.
⁸ Medical Imaging Centre Cobalt Medical Charity, Cheltenham, UK.
⁹ Cranfield University, Cranfield, Wiltshire, UK.
¹⁰ Central and East London Breast Screening Services, Royal Free London NHS Foundation Trust, London, England, UK.
¹¹ Division of Clinical Medicine, The University of Sheffield Medical School, Sheffield, UK.
¹² National Radiotherapy Trials QA Group, Mount Vernon Cancer Centre, Northwood, England, UK.
¹³ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England, UK.
¹⁴ School of Cancer and Pharmaceutical Sciences, King's College London, London, England, UK.
¹⁵ Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
¹⁶ Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, England, UK.
¹⁷ Bristol Breast Care Centre, Southmead Hospital, Bristol, England, UK.
¹⁸ Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England, UK.
¹⁹ Breast Unit, St James's Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, Leeds, UK.
²⁰ Independent Cancer Patients' Voice, London, UK.
²¹ Wrightington Wigan and Leigh NHS Foundation Trust, Wigan, UK.
²² Warwick Medical School, University of Warwick, Coventry, England, UK.
²³ Central and East London Breast Screening Service, Royal Free London NHS Foundation Trust, London, England, UK.
²⁴ Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, UK.
²⁵ NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, UK.
²⁶ Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK s.mcintosh@qub.ac.uk.

PMID: 40204306
PMCID: PMC11979497
DOI: 10.1136/bmjopen-2025-099702

Comparative Study

SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Kenneth Elder et al. BMJ Open. 2025.

. 2025 Apr 8;15(4):e099702.

doi: 10.1136/bmjopen-2025-099702.

Authors

Affiliations

¹ Breast Unit, Western General Hospital, Edinburgh, UK.
² Department of Oncology, University of Cambridge, Cambridge, UK.
³ Population Health, University of Oxford, Oxford, UK.
⁴ Aberdeen Royal Infirmary, Aberdeen, UK.
⁵ Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
⁶ Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool, UK.
⁷ Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.
⁸ Medical Imaging Centre Cobalt Medical Charity, Cheltenham, UK.
⁹ Cranfield University, Cranfield, Wiltshire, UK.
¹⁰ Central and East London Breast Screening Services, Royal Free London NHS Foundation Trust, London, England, UK.
¹¹ Division of Clinical Medicine, The University of Sheffield Medical School, Sheffield, UK.
¹² National Radiotherapy Trials QA Group, Mount Vernon Cancer Centre, Northwood, England, UK.
¹³ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England, UK.
¹⁴ School of Cancer and Pharmaceutical Sciences, King's College London, London, England, UK.
¹⁵ Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
¹⁶ Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, England, UK.
¹⁷ Bristol Breast Care Centre, Southmead Hospital, Bristol, England, UK.
¹⁸ Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England, UK.
¹⁹ Breast Unit, St James's Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, Leeds, UK.
²⁰ Independent Cancer Patients' Voice, London, UK.
²¹ Wrightington Wigan and Leigh NHS Foundation Trust, Wigan, UK.
²² Warwick Medical School, University of Warwick, Coventry, England, UK.
²³ Central and East London Breast Screening Service, Royal Free London NHS Foundation Trust, London, England, UK.
²⁴ Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, UK.
²⁵ NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, UK.
²⁶ Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK s.mcintosh@qub.ac.uk.

PMID: 40204306
PMCID: PMC11979497
DOI: 10.1136/bmjopen-2025-099702

Abstract

Introduction: Mammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as 'overdiagnosed' cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL (Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers.

Methods: SMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.

Ethics and dissemination: Ethical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.

Trial registration number: ISRCTN12240119.

Keywords: Breast imaging; Breast surgery; Breast tumours; Clinical Trial.

PubMed Disclaimer

Conflict of interest statement

Competing interests: SM reports speaker honoraria from MSD, Roche, BD, Astra Zeneca, Veracyte and Exact Sciences; advisory boards for Lilly, Novartis, MSD, Roche and Astra Zeneca; conference travel and support from Roche, Lilly and MSD, and institutional research funding from Novartis. S Pinder reports honoraria from Roche, Astra Zeneca, Exact Sciences and Daiichi-Sankyo; advisory board for Exact Science. NS reports speaker honoraria from BD and Hologic. The remaining authors have no competing interests to declare.

Figures

Figure 1. SMALL (**Open Surgery versus minimally invasive-vacuum assisted excision for small screen-detected breast cancer**) trial schema showing key eligibility criteria. DCIS, ductal carcinoma in situ; ER, oestrogen receptor; HER2, human epidermal growth factor receptor type 2; PR, progesterone receptor; VAE, vacuum-assisted excision; ISH, in situ hybridisation; IHC, immunohistochemistry; SLNB, sentinel lymph node biopsy.

See this image and copyright information in PMC

References

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin . 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
1. Bray F, McCarron P, Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 2004;6:229–39. doi: 10.1186/bcr932. - DOI - PMC - PubMed
1. Quinn M, Allen E. Changes in incidence of and mortality from breast cancer in England and Wales since introduction of screening. United Kingdom Association of Cancer Registries. BMJ. 1995;311:1391–5. doi: 10.1136/bmj.311.7017.1391. - DOI - PMC - PubMed
1. Narod SA, Iqbal J, Miller AB. Why have breast cancer mortality rates declined? J Cancer Policy. 2015;5:8–17. doi: 10.1016/j.jcpo.2015.03.002. - DOI
1. Shapiro S, Strax P. Periodic Breast Cancer Screening in Reducing Mortality From Breast Cancer. JAMA . 1971;215:1777. doi: 10.1001/jama.1971.03180240027005. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- PubMed Central
- White Rose Research Online
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Affiliations

SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical