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.

Keywords: breast cancer; family history; genes; prevention; risk; screening.

Figure 1

Annual referrals to the Manchester FHC between 1987 and 2020. Increases in referral were seen during the period when the first breast cancer genes, TP53 and BRCA1/2, were identified and also related to the publicity surrounding Angelina Jolie when she indicated that she was a BRCA1 PV carrier. The increase in median body mass index (BMI) and median age at first full-term pregnancy (FFTP) over this period are shown. Over the period of 33 years, lifetime risk of BC in the population increased from 1 in 12 to 1 in 8, an increase presumed to be associated with change in modifiable risk factors. These trends were apparent in the FHC. For example, the median age of first full-term pregnancy increased from 24 years to 27 years (p < 0.001), and median BMI at clinic entry increased from 23.7 to 24.8 kg/m² (p < 0.001).