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Breast Cancer Research

Open Access

The future of breast cancer prevention

  • A Howell1,
  • A Sims1,
  • M Harvie1,
  • KR Ong1,
  • G Evans1 and
  • R Clarke1
Breast Cancer Research20057(Suppl 2):S.09

https://doi.org/10.1186/bcr1052

Published: 17 June 2005

Keywords

Breast CancerTamoxifenBreast Cancer RiskMammographic DensityContralateral Breast Cancer

At present, large numbers of at-risk women are treated in order to prevent relatively small numbers of breast cancers. There is a need to define risk more precisely in order to target interventions and a need to improve their efficacy. Risk estimations currently depend upon integration of familial and endocrine risk factors. We have demonstrated that the Tyrer–Cuzick model that takes both factors into account more fully is superior to other risk prediction models in our clinic [1]. However, prediction remains imprecise for the individual. Attempts are being made to take additional risk factors into account, including mammographic density [2], serum estradiol concentration and bone density. It seems probable that a better understanding of the interactions between stromal and epithelial cells in the breast including fibroblasts, adipocytes, macrophages and blood vessels will ultimately lead to better prediction. We have shown that 5% loss of body weight during mid life reduces postmenopausal breast cancer risk by 40% [3], and overviews indicate that use of NSAIDs [4] and exercise [5] may reduce risk by approximately 30%. The mechanisms of these risk reductions are not clear but gene array studies indicate that calorie restriction and exercise predominantly reduce the expression of genes related to inflammation [6, 7]. This raises the question of whether all these interventions act by similar mechanisms. A better understanding of the mechanisms of mammographic density and mammary cell senescence is required. Both are associated with fibroblasts that increase and stimulate proliferation of local epithelial cells [8, 9]. Since mammographic density is a major risk factor, its reversal is likely to be beneficial. Another stromal target is aromatase. All adjuvant aromatase inhibitor (AI) trials have shown an approximately 50% contralateral breast cancer reduction compared with tamoxifen [10]. Since tamoxifen reduces contralateral risk by about 50% compared with placebo, AIs may reduce risk by 70–80%. Trials to test this hypothesis are underway (IBIS II, MAP3). The aforementioned considerations indicate that the stroma and stroma–epithelial interactions are already targets for preventive measures, and this is likely to expand and lead to new interventions such as NF-κB inhibition [11] and SIRT1 activation [12].

Authors’ Affiliations

(1)
CRUK Department of Medical Oncology, University of Manchester, Christie Hospital, Manchester, UK

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Copyright

© BioMed Central 2005

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