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Breast. 2018 Jun;39:139-147. doi: 10.1016/j.breast.2018.03.009. Epub 2018 Mar 30.

Personalized prevention in high risk individuals: Managing hormones and beyond.

Author information

1
Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Prevent Breast Cancer and Nightingale Breast Screening Centre, Wythenshawe Hospital Manchester Universities Foundation Trust, Manchester, UK; Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK; Manchester Breast Centre, Manchester Cancer Research Centre, University of Manchester, Manchester, UK. Electronic address: gareth.evans@cmft.nhs.uk.
2
Prevent Breast Cancer and Nightingale Breast Screening Centre, Wythenshawe Hospital Manchester Universities Foundation Trust, Manchester, UK; Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK; Manchester Breast Centre, Manchester Cancer Research Centre, University of Manchester, Manchester, UK.

Abstract

Increasing numbers of women are being identified at 'high-risk' of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold. The options for risk reduction in such women include endocrine chemoprevention with the selective estrogen receptor modulators tamoxifen and raloxifene or the aromatase inhibitors anastrozole or exemestane. NICE recommends offering anastrozole to postmenopausal women at high-risk of breast cancer as cost effectiveness analysis showed this to be cost saving to the National Health Service. Overall uptake to chemoprevention has been disappointingly low but this may improve with the improved efficacy of aromatase inhibitors, particularly the lack of toxicity to the endometrium and thrombogenic risks. Novel approaches to chemoprevention under investigation include lower dose and topical tamoxifen, denosumab, anti-progestins and metformin. Although oophorectomy is usually only recommended to women at increased risk of ovarian cancer it has been shown in numerous studies to reduce breast cancer risks in the general population and in those with mutations in BRCA1/2. However, recent evidence from studies that have confined analysis to true prospective follow up have cast doubt on the efficacy of oophorectomy to reduce breast cancer risk in BRCA1 mutation carriers, at least in the short-term.

KEYWORDS:

Anastrazole; BRCA1; BRCA2; Breast cancer; Chemoprevention; Oophorectomy; Tamoxifen

PMID:
29610032
DOI:
10.1016/j.breast.2018.03.009
[Indexed for MEDLINE]

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