Personalized prevention in high risk individuals: Managing hormones and beyond

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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. Aim: To describe indications and results of BSO, and data on endocrine prevention of BC in high risk individuals.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalBreast (Edinburgh, Scotland)
Early online date30 Mar 2018
Publication statusPublished - Jun 2018


  • Journal Article
  • Anastrazole
  • Oophorectomy
  • Chemoprevention
  • Breast cancer
  • BRCA1
  • BRCA2
  • Tamoxifen
  • Humans
  • Middle Aged
  • Tamoxifen/therapeutic use
  • Chemoprevention/methods
  • Genes, BRCA2
  • Adult
  • Female
  • Genes, BRCA1
  • Raloxifene Hydrochloride/therapeutic use
  • Triazoles/therapeutic use
  • Antineoplastic Agents, Hormonal/therapeutic use
  • Precision Medicine/methods
  • Risk Assessment
  • Anastrozole
  • Risk Factors
  • Nitriles/therapeutic use
  • Mammography/methods
  • Early Detection of Cancer/methods
  • Breast Neoplasms/genetics
  • Androstadienes/therapeutic use

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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