Long-Term Evaluation of Women Referred to a Breast Cancer Family History Clinic (Manchester UK 1987–2020)

Abstract

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987–2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (≥30% lifetime risk), 37.7% at moderate risk (17–29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14–27% entered various lifestyle studies. From 1992–2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention; 10.8% women took up the offer of such treatment between 2013–2020. Since 1994, 7164 eligible women at ≥25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results.

Clinical utility of testing for PALB2 and CHEK2 c.1100delC in breast and ovarian cancer

“…Women were either referred for genetic testing to the Manchester Center for Genomic Medicine (MCGM) or the Family History Risk and Prevention Clinic (FHRPC) at the Nightingale Center, Wythenshawe Hospital ( n = 2,603). 14 In addition, 524 women were tested as part of the population based Predicting the Risk Of Cancer At Screening (PROCAS) study, in Greater Manchester. 15 Demographic details of the study population are outlined in Table 1 .…”

Breast cancer incidence and early diagnosis in a family history risk and prevention clinic: 33-year experience in 14,311 women

“…Women with a breast cancer family history, but unaffected personally, have been referred to the FHRPC at the Nightingale Centre Withington/Wythenshawe hospital since 1987. Their lifetime and residual risk of breast cancer has been assessed using questionnaire information on family history and standard risk factors using Claus tables and the Tyrer–Cuzick programme [ 2 , 7 – 9 , 23 , 24 ]. Women were classified as being high-risk (lifetime-risk ≥ 30%), moderate-risk (lifetime-risk 17–29%) or average/population risk (lifetime-risk < 17%).…”

“…A family history risk and prevention clinic (FHRPC) to improve early detection and preventive approaches was established in Manchester in 1987 [2] and was the forerunner to other similar clinics across the UK and in Europe. In-house [3] and national [4] management guidelines were developed and, in, the UK, endorsed by a series of guidelines by the National Institute for Health and Care Excellence (NICE 2004(NICE , 2006(NICE , 2013(NICE , 2017 [5] in response to clinical developments in risk assessment, genetic testing, screening, preventive therapy and risk reducing surgery.…”

“…Preventive therapy using tamoxifen and raloxifene was endorsed in the 2013 NICE guideline and anastrozole in 2017 [ 5 , 21 , 22 ]. The uptake of risk reducing breast surgery has gradually increased since its introduction in the UK in the early 1990’s [ 2 ].…”

Special Issue “Gynaecological Cancers Risk: Breast Cancer, Ovarian Cancer and Endometrial Cancer”

“…Trebo et al [ 16 ] establish that high Galectin-7 and low Galectin-8 expression are poor prognostic markers for breast cancer, highlighting the need for more research to comprehend the role of galectins in the regulation and interaction of tumor cells and macrophages. Howell et al [ 17 ] describe risk assessment and management outcomes of one of the largest cohorts of women (14,311) seen in a tertiary-level high-risk service for women at increased risk of breast cancer.…”