What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420).

Background: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms).

Breast cancer pathology and stage are better predicted by risk stratification models that include mammographic density and common genetic variants.

Purpose: To improve breast cancer risk stratification to enable more targeted early detection/prevention strategies that will better balance risks and benefits of population screening programmes.

Methods: 9362 of 57,902 women in the Predicting-Risk-Of-Cancer-At-Screening (PROCAS) study who were unaffected by breast cancer at study entry and provided DNA for a polygenic risk score (PRS). The PRS was analysed alongside mammographic density (density-residual-DR) and standard risk factors (Tyrer-Cuzick-model) to assess future risk of breast cancer based on tumour stage receptor expression and pathology.

Psychological impact of providing women with personalised 10-year breast cancer risk estimates.

Background: The Predicting Risk of Cancer at Screening (PROCAS) study estimated 10-year breast cancer risk for 53,596 women attending NHS Breast Screening Programme. The present study, nested within the PROCAS study, aimed to assess the psychological impact of receiving breast cancer risk estimates, based on: (a) the Tyrer-Cuzick (T-C) algorithm including breast density or (b) T-C including breast density plus single-nucleotide polymorphisms (SNPs), versus (c) comparison women awaiting results.

Methods: A sample of 2138 women from the PROCAS study was stratified by testing groups: T-C only, T-C(+SNPs) and comparison women; and by 10-year risk estimates received: 'moderate' (5-7.

A comparison of five methods of measuring mammographic density: a case-control study.

Background: High mammographic density is associated with both risk of cancers being missed at mammography, and increased risk of developing breast cancer. Stratification of breast cancer prevention and screening requires mammographic density measures predictive of cancer. This study compares five mammographic density measures to determine the association with subsequent diagnosis of breast cancer and the presence of breast cancer at screening.

Breast cancer risk in a screening cohort of Asian and white British/Irish women from Manchester UK.

Background: The differences between breast cancer risk factors in white British/Irish and Asian women attending screening in the UK are not well documented.

Methods: Between 2009-15 ethnicity and traditional breast cancer risk factors were self-identified by a screening cohort from Greater Manchester, with follow up to 2016. Risk factors and incidence rates were compared using age-standardised statistics (European standard population).

The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study.

Background: Breast cancer familial risk clinics offer screening and preventive strategies. While BRCA1/BRCA2 genetic testing provides important risk information for some women, panels of more common breast cancer risk genetic variants may have relevance to greater numbers of women with familial risk.

Methods: Three polygenic risk scores (PRS) based on 18 SNPs were investigated in a case-control study of women attending a familial risk clinic.

Breast cancer risk feedback to women in the UK NHS breast screening population.

Introduction: There are widespread moves to develop risk-stratified approaches to population-based breast screening. The public needs to favour receiving breast cancer risk information, which ideally should produce no detrimental effects. This study investigates risk perception, the proportion wishing to know their 10-year risk and whether subsequent screening attendance is affected.

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort.

Introduction: The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model).

Methods: Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index.

Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography.

Women from breast cancer families without a demonstrable BRCA1/2 mutation were subjected to annual mammography from age 30 years onwards. One-hundred and ninety-eight patients were diagnosed prospectively with invasive breast cancer and followed for a total of 1513 years. Overall 10-year survival was 88 %.

Breast cancer risk in young women in the national breast screening programme: implications for applying NICE guidelines for additional screening and chemoprevention.

In the United Kingdom, women at moderate and high risk of breast cancer between the ages of 40 and 49 years are eligible for annual mammographic screening and preventive therapy with tamoxifen. Here, we estimate the numbers of women in a population eligible for this service and the proportion of breast cancers detected in this group compared with the whole population. Women <50 attending for mammographic screening in the National Health Service Breast Screening Programme (NHSBSP) completed a risk questionnaire.

Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

Background: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews.

Breast cancer risk assessment in 8,824 women attending a family history evaluation and screening programme.

Accurate individualized breast cancer risk assessment is essential to provide risk-benefit analysis prior to initiating interventions designed to lower breast cancer risk and start surveillance. We have previously shown that a manual adaptation of Claus tables was as accurate as the Tyrer-Cuzick model and more accurate at predicting breast cancer than the Gail, Claus model and Ford models. Here we reassess the manual model with longer follow up and higher numbers of cancers.

Assessing individual breast cancer risk within the U.K. National Health Service Breast Screening Program: a new paradigm for cancer prevention.

The aim of this study is to determine breast cancer risk at mammographic screening episodes and integrate standard risk factors with mammographic density and genetic data to assess changing the screening interval based on risk and offer women at high risk preventive strategies. We report our experience of assessing breast cancer risk within the U.K.

Prevention of breast cancer in the context of a national breast screening programme.

Breast cancer is not only increasing in the west but also particularly rapidly in eastern countries where traditionally the incidence has been low. The rise in incidence is mainly related to changes in reproductive patterns and lifestyle. These trends could potentially be reversed by defining women at greatest risk and offering appropriate preventive measures.

Carcinosarcoma arising in eccrine spiradenoma. A clinicopathologic and immunohistochemical study of two cases.

Malignant change in a benign eccrine spiradenoma is rare. Only 13 such cases have been previously reported. Two further cases are described herein, both of which were carcinosarcomas and arose in middle-aged women.