Title: Breast Screening Atypia: Observational Analysis of Subsequent Development of Cancer using Sloane UK database (Sloane Atypia)
Funder: Department of Health and Social Care

Abstract: Research Question What is the risk for women diagnosed with atypia of developing breast cancer at 1, 3 and 6 years after diagnosis? How does it vary by type of atypia and over time? What are the types of cancer that develop (by grade and stage and other prognostic markers)? This will be used to review policy options for surveillance, including annual mammography for 5 years. Background England s NHS Breast Screening Programme aims to balance increasing the early detection of breast cancer with reducing overdiagnosis. As well as breast cancer, atypical epithelial proliferations (atypia) can also be detected as part of screening. These are not cancer, but may mean that a woman is more likely to develop breast cancer in the future. If atypia is observed during a screening round then at present the woman may be invited to be screened annually for the next five years, rather than being invited back in three years. This is not evidence based. We currently do not know which atypia should be detected, the risk of developing subsequent cancer or which type of cancers develop. This study will explore 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. Aims and Objectives To characterise atypia in terms of type, method of investigation and women s demographics; To determine breast cancer risk over time by type of atypia; To characterise the nature of subsequent cancers detected, and their prognosis; To communicate results to clinicians and women; To recommend changes to the NHSBSP quality standards. Methods The Sloane Atypia Audit Project began in April 2003 with ongoing data collection on atypia diagnosed through screening. As of 24 September 2020, the database includes 3,043 cases of epithelial atypia that meet the study inclusion and exclusion criteria, with follow-up from 1 to 15 years. The outcomes are: subsequent invasive breast cancer (combined and then split into ipsilateral and contralateral) and the nature of subsequent cancer. Descriptive statistics will be produced. The observed rates of breast cancer at 1, 3 and 6 years for three types of atypia will be compared together and separately, through their confidence intervals, to the rate of breast cancer in women in the general population. Time to event methods will be used to describe the time to breast cancer diagnosis for the different types of atypia, including flexible parametric modelling if appropriate. Timelines for delivery Analysis will be completed by end of 2021, with dissemination complete by end of August 2022. Anticipated Impact and Dissemination The study will be disseminated to the NHS Breast Screening Programme, giving them evidence to assist in updating their guidelines; to breast screening commissioners and clinicians through workshops, journal articles and conferences; and to the general public, through a website and PPI focus groups.

Lay abstract: In England we offer breast screening every three years to women aged 50 to 70 years. In 2018/19 the NHS breast cancer screening programme screened over two million women. Cancer is detected in nearly 20,000 of these women but a small proportion have types of abnormality that are not cancer. These are called atypical epithelial proliferations, or atypia. Whilst these women do not have cancer, some of them may be more likely to develop cancer in the future than women without atypia. There are different types of atypia and the risk of developing cancer varies by type of atypia. However, we currently do not know what the true risk is for these women. We do not know how many of these women will develop cancer, or how long it will take and the types of cancer if it does develop. Because of this uncertainty there are no national guidelines and, therefore, care across the UK varies. Some screening centres offer women with atypia, regardless of type, mammograms, every year for 5 years. Other centres continue to offer routine 3-yearly mammograms. We do not know what is the best care for women. Some women may be unnecessarily investigated and diagnosed with atypia which would not have caused any harm within the woman s lifetime. This is called overdiagnosis which leads to overtreatment and unnecessary worry. Mammography can also cause discomfort and anxiety. We propose a research project using data from women in England who have had atypia in the last 17 years. We want to find out: 1) how many women develop cancer; 2) at what time they develop cancer; 3) the type and severity of cancer. We also want to investigate to what degree this information differs depending on the type of atypia. We are working with women who have experienced screening and breast cancer. They have helped us decide on the research questions. They will also work with us throughout the project. This new knowledge will help to improve the care offered to women with atypia. We believe this is possible by offering more mammograms to women whose atypia is likely to develop into an aggressive breast cancer and avoiding the harm from overinvestigation and overdiagnosis to those women who do not need more tests. We will publish our results and use them to advise the NHS Breast Screening Programme about what should be recommended for women diagnosed with atypia. We will also report results to the breast screening centres and provide lay summaries for women and the public. What we do at the moment is not based on research evidence, so our findings could have a large influence on breast screening practice.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS