Clinical trial NCT05402436: Breast Screening Atypia and Subsequent Development of Cancer in England
Official title: Breast Screening Atypia and Subsequent Development of Cancer: an Observational Analysis of the Sloane Database in England (Sloane Atypia Cohort Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: Screening
Observational
Lead sponsor: University of Warwick
Sponsor class: OTHER
Collaborators: name: University Hospitals Coventry and Warwickshire NHS Trust
name: King's College London
name: The Leeds Teaching Hospitals NHS Trust
First posted: 2022-06-02
Enrollment: 3238
Sex: FEMALE
Minimum age (years): 47
Maximum age (years): 73
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Women with atypia diagnosed during breast cancer screening in England between 1st January 2003 and 30th June 2018.

Brief summary: During breast screening, atypical epithelial proliferations (atypia) can be detected. These are not cancer, but may mean that a woman is more likely to develop breast cancer in the future. This study explores how atypia develop into breast cancer in terms of number of women, time to cancer development, cancer type and severity, and whether this varies for different types of atypia. The results will be used to create new guidelines for how women with atypia should be followed up.

Detailed description: In England, breast cancer screening is offered every three years to women aged 50 to 70. In an increasing number of women atypical epithelial proliferations (atypias) are detected. Atypias are a heterogeneous group of abnormalities, which are not cancer but carry a low but significant rate of associated malignancy. Detecting these lesions has uncertain benefit because of insufficient evidence on their risk of subsequent development into breast cancer. This information is key to optimising follow-up and subsequent screening. This study undertakes the first analysis of the Sloane atypia data by reporting the proportion of women with atypia who develop breast cancer by type of atypia (atypical ductal hyperplasia (ADH) or atypical intraductal epithelial proliferation (AIDEP), flat epithelial atypia (FEA), and lobular in situ neoplasia (LISN: atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS)) and in what time frame.

This large-scale study of atypia uses the English screening programme data from the Sloane cohort study. The Sloane atypia project is a prospective cohort of atypia diagnosed through the UK NHS Breast Screening Programme from April 2003 to the present. For this analysis, English screening units are included with radiology, histopathology, surgery and radiotherapy proformas. Subsequent development of breast cancer has been identified by matching women by NHS number and date of birth to the English Cancer Registry held by the National Cancer Registration and Analysis Service (NCRAS). The atypia cases are also matched to the Mortality and Birth Information System to collect mortality data for censoring follow-up, and the Breast Screening Data Repository for information on invitation and attendance at subsequent screening mammography appointments.

Study objectives are:

1. To characterise atypia in terms of type, method of investigation and women's demographics;
2. To determine breast cancer risk over time by type of atypia;
3. To characterise the nature of subsequent cancers detected, and their prognostic features;
4. To communicate results to clinicians and women;
5. To recommend changes to the NHS Breast Screening Programme quality standards.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of epithelial atypia (ADH (including AIDEP), LISN (both ALH and LCIS) and FEA) in the Sloane database between 1st January 2003 and 30th June 2018

Exclusion Criteria:

* bilateral primary cases
* the "best prognosis" atypia of the bilateral primaries
* atypia with co-existing DCIS
* pleomorphic LCIS (as these are managed akin to DCIS)
* unknown type of atypia
* cases not from England
* patients without follow-up until 31 December 2018

Primary outcomes:
measure: Invasive breast cancer at 3 years following atypia diagnosis
timeFrame: Cumulative incidence of invasive breast cancer with all cause mortality as a competing risk at 3 years following atypia diagnosis
measure: Invasive breast cancer at 6 years following atypia diagnosis
timeFrame: Cumulative incidence of invasive breast cancer with all cause mortality as a competing risk at 6 years following atypia diagnosis
Secondary outcomes:
measure: Invasive breast cancer at 1-year following atypia diagnosis
timeFrame: Cumulative incidence of invasive breast cancer with all cause mortality as a competing risk at 1-year following atypia diagnosis
measure: Invasive cancer or non-invasive cancer (Ductal carcinoma in situ (DCIS)) at 1 year following atypia diagnosis
timeFrame: Cumulative incidence of invasive breast cancer or DCIS with all cause mortality as a competing risk at 1 year following atypia diagnosis
measure: Invasive cancer or non-invasive cancer (Ductal carcinoma in situ (DCIS)) at 3 years following atypia diagnosis
timeFrame: Cumulative incidence of invasive breast cancer or DCIS with all cause mortality as a competing risk at 3 years following atypia diagnosis
measure: Invasive cancer or non-invasive cancer (Ductal carcinoma in situ (DCIS)) at 6 years following atypia diagnosis
timeFrame: Cumulative incidence of invasive breast cancer or DCIS with all cause mortality as a competing risk at 6 years following atypia diagnosis
Other outcomes:
Locations:
city: Coventry
country: United Kingdom
facility: Univesity of Warwick
state: Warwickshire
Study officials:
References:
citation: Jenkinson D, Freeman K, Clements K, Hilton B, Dulson-Cox J, Kearins O, Stallard N, Wallis MG, Sharma N, Kirwan C, Pinder S, Provenzano E, Shaaban AM, Stobart H, McDonnell S, Thompson AM, Taylor-Phillips S. Breast screening atypia and subsequent development of cancer: protocol for an observational analysis of the Sloane database in England (Sloane atypia cohort study). BMJ Open. 2022 Jan 7;12(1):e058050. doi: 10.1136/bmjopen-2021-058050.
citation: Freeman K, Mansbridge A, Stobart H, Clements K, Wallis MG, Pinder SE, Kearins O, Shaaban AM, Kirwan CC, Wilkinson LS, Webb S, O'Sullivan E, Jenkins J, Wright S, Taylor K, Bailey C, Holcombe C, Wyld L, Edwards K, Jenkinson DJ, Sharma N, Provenzano E, Hilton B, Stallard N, Thompson AM, Taylor-Phillips S. Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project. Br J Radiol. 2024 Feb 2;97(1154):324-330. doi: 10.1093/bjr/tqad053.
citation: Freeman K, Jenkinson D, Clements K, Wallis MG, Pinder SE, Provenzano E, Stobart H, Stallard N, Kearins O, Sharma N, Shaaban A, Kirwan CC, Hilton B, Thompson AM, Taylor-Phillips S; Sloane Project Steering Group. Atypia detected during breast screening and subsequent development of cancer: observational analysis of the Sloane atypia prospective cohort in England. BMJ. 2024 Feb 1;384:e077039. doi: 10.1136/bmj-2023-077039.