Anastrozole for breast cancer prevention

Anastrozole for breast cancer prevention

• IBIS-II - an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 year (1)
  
  
• Cuzick et al reported results of the randomised IBIS-II trial on the extended duration of benefit of anastrozole in preventing breast cancer up to 12 years after entry and indicate for the first time a long-term benefit, which is larger than that seen for tamoxifen in this period
  • anastrozole is an aromatase inhibitor - inhibition of aromatase prevents the synthesis of oestrogens
  • no excess of fractures, other cancers, cardiovascular disease, or death from any specific cause was seen in the extended follow-up
  • number needed to treat to prevent one breast cancer is 29
    • large 61% reduction in breast cancer incidence in the first 5 years has been maintained in subsequent follow-up to 12 years
    • the significant 36% reduction during post-treatment follow-up was not significantly smaller than during treatment, and still greater than that observed for tamoxifen, which has produced a roughly constant 29% reduction for 20 years
    • number needed to treat to prevent one breast cancer during the first 12 years of follow-up was 29, which compares favourably with the 58 needed for tamoxifen at that time
  • previously observed reduction of other cancers with anastrozole, notably non-melanoma skin cancer, has continued with longer follow up
  • results provide additional support for the use of anastrozole as the treatment of choice for breast cancer risk reduction in most postmenopausal women at high risk of developing breast cancer

NICE guidance states (2):

Chemoprevention for women with no personal history of breast cancer

• should be discussed within a specialist genetic clinic
  • healthcare professionals within a specialist genetic clinic should discuss and give written information on the absolute risks and benefits of all options for chemoprevention to women at high risk or moderate risk of breast cancer
  • discussion and information should include the side effects of drugs, the extent of risk reduction, and the risks and benefits of alternative approaches, such risk-reducing surgery and surveillance
    
    
• recommendations about chemoprevention for women at high risk of breast cancer
  
  
  • tamoxifen should be offered for 5 years to premenopausal women at high risk of breast cancer unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer
    
    
  • anastrozole should be offered for 5 years to postmenopausal women at high risk of breast cancer unless they have severe osteoporosis.
    
    
  • for postmenopausal women at high risk of breast cancer who have severe osteoporosis or do not wish to take anastrozole:
    • offer tamoxifen for 5 years if they have no history or increased risk of thromboembolic disease or endometrial cancer, or
    • consider raloxifene for 5 years for women with a uterus if they have no history or increased risk of thromboembolic disease and do not wish to take tamoxifen
      
      
  • do not offer chemoprevention to women who were at high risk of breast cancer but have had bilateral risk-reducing mastectomy
    
    
• recommendations about chemoprevention for women at moderate risk of breast cancer (2)
  
  
  • tamoxifen should be considered for 5 years for premenopausal women at moderate risk of breast cancer, unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer
    
    
  • anastrozole should be considered for 5 years for postmenopausal women at moderate risk of breast cancer unless they have severe osteoporosis
    
    
  • for postmenopausal women at moderate risk of breast cancer who have severe osteoporosis or do not wish to take anastrozole:
    
    
    • consider tamoxifen for 5 years if they have no history or increased risk of thromboembolic disease or endometrial cancer, or
      
      
    • consider raloxifene for 5 years for women with a uterus if they have no history or increased risk of thromboembolic disease and do not wish to take tamoxifen
      
      
• do not continue chemoprevention beyond 5 years in women with no personal history of breast cancer
  
  
• inform women that they should stop tamoxifen at least:
  • 2 months before trying to conceive
  • 6 weeks before elective surgery

Breast cancer risk category

*This group includes known BRCA1, BRCA2 and TP53 mutations and rare conditions that carry an increased risk of breast cancer such as Peutz-Jegher syndrome (STK11), Cowden (PTEN) and familial diffuse gastric cancer (E-Cadherin)

Notes:

• at the time of publication (June 2013), tamoxifen did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices for further information.
• at the time of publication (June 2013), raloxifene did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices for further information
• NHS England estimate that around 3.7% of the female population in England between 30-60 years old are eligible for preventative therapy for breast cancer (3)

Reference:

• Cuzick J, Sestak I, Forbes JF, Dowsett M, Cawthorn S, Mansel RE, Loibl S, Bonanni B, Evans DG, Howell A; IBIS-II investigators. Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet. 2020 Jan 11;395(10218):117-122. doi: 10.1016/S0140-6736(19)32955-1.
• NICE (March 2017). Familial breast cancer: classifification, care and managing breast cancer and related risks in people with a family history of breast cancer
• NHS. Pathway Transformation Fund 2020/21 Guidance for Tamoxifen Rapid Uptake Pathway (accessed 29/6/21)