• The endocrine prevention of breast cancer.

      Howell, Anthony; CRUK Department of Medical Oncology, Christie Hospital, Manchester M20 4BX, UK. anthony.howell@christie.nhs.uk (2008-08)
      Breast cancer incidence is increasing in all parts of the world. Although in Western countries death rates are declining, there is a need to make attempts to prevent the disease in order to reduce the trauma of diagnosis and treatment. Endocrine approaches to breast cancer prevention have been the most successful approach to cancer prevention to date. Studies with tamoxifen were initiated when it was noted that, during adjuvant treatment after surgery to prevent relapse, the incidence of new contralateral cancers was reduced by half. Four trials of >or=5 years of tamoxifen compared with placebo in women at increased risk of breast cancer were initiated in the 1980s and showed a similar reduction in breast cancer, but only in oestrogen-receptor-positive disease. Recent follow-up indicated that there is a carry-over effect of tamoxifen after the completion of treatment at 5 years so that the preventive effect at 10 years is significantly great than at 5. The selective oestrogen receptor modulator (SERM) raloxifene has also been assessed as a preventive agent in two major international randomized trials compared with placebo and shows a protective effect similar to that of tamoxifen. An American study subsequently compared tamoxifen and raloxifene in a trial of nearly 20,000 women at increased risk (the STAR trial) and demonstrated that the two agents were equally effective but that the toxicity of raloxifene was less. Adjuvant trials comparing tamoxifen and the modern potent aromatase inhibitors (anastrozole, letrozole and exemestane) indicate that they are superior to tamoxifen and reduce contralateral breast cancer by approximately 70%. This observation has led to the initiation of two trials in postmenopausal women comparing anastrozole (the IBISII trial) or exemestane (the MAP-3 trial) with placebo. Currently it is recommended that tamoxifen is used to prevent breast cancer in premenopausal women and raloxifene for postmenopausal women (it is not effective in the premenopausal group),and we await the results of the aromatase inhibitor trials.
    • Preventive therapy for breast cancer: a consensus statement.

      Cuzick, J; DeCensi, A; Arun, B; Brown, P; Castiglione, M; Dunn, B; Forbes, J; Glaus, A; Howell, Anthony; Von Minckwitz, G; et al. (2011-05)
      In March, 2010, a group of breast cancer experts met to develop a consensus statement on breast cancer prevention, with a focus on medical and therapeutic interventions. We present the conclusions in this Review. First we agreed that the term chemoprevention is inappropriate and suggested that the term preventive therapy better represents this feature of management. Two selective oestrogen-receptor modulators--tamoxifen and raloxifene--are so far the only medical options approved by the US Food and Drug Administration for preventive therapy. Of these tamoxifen has greater efficacy and can be used in premenopausal women, but raloxifene has fewer side-effects. Two newer drugs in this class, lasofoxifene and arzoxifene, also show efficacy and possibly a better overall risk-benefit profile, but need further assessment. Aromatase inhibitors might be more efficacious, and results of prevention trials are eagerly awaited. Newer agents, notably bisphosphonates and metformin, have shown promise in observational studies and need to be assessed in randomised prevention trials. Other agents, such as aspirin, other non-steroidal anti-inflammatory drugs, COX-2 inhibitors, retinoids, rexinoids, and dietary components have limited effects or are in the early phases of investigation. New contralateral tumours in women with breast cancer might be generally useful as a model for prevention, as has been seen for tamoxifen. If valid such a model would facilitate the design of simpler, cheaper, and better-focused trials for assessing new agents.