Prevention of Breast Cancer

Both raloxifene and tamoxifen are approved for the prevention of breast cancer in the United States. Evidence supporting anti-estrogens for the prevention of breast cancer is substantial. A meta-analysis of the five large prevention trials demonstrated a 42% reduction of breast cancer risk with tamoxifen when compared to placebo.1In otherwise healthy women who are using tamoxifen for breast cancer prevention, up to 40% do not continue it because of side effects including depression and mood changes.2-7An increase in the risk of endometrial cancer also limits the use of tamoxifen.

Another SERM (Selective Estrogen Receptor Modulator) raloxifene reduces the risk of breast cancer without increasing the risk of endometrial cancer. The STAR trial compared raloxifene and tamoxifen in a prevention trial of 18,000 postmenopausal women with a predicted risk of more than 1.67% at 5 years. Both agents prevented invasive breast cancer by an estimated 50% but raloxifene but raloxifene exhibited a superior toxicity profile with 30% fewer thromboembolic events 38% fewer endometrial cancers 21% fewer cataracts, an 84% reduction in uterine hyperplasia and 55% fewer hysterectomies.7,8Long term follow-up of the STAR trial demonstrated that tamoxifen was superior to raloxifene in preventing invasive breast cancer. This later study clearly demonstrates the superiority of of tamoxifen over raloxifene for the prevention of breast cancer albeit with a greater risk of endometrial cancer.9However, current guidelines suggest that raloxifene may be preferred to tamoxifen in women with a uterus.

Breast Cancer ImagingClearly, tamoxifen is far from the ideal agent for the prevention of breast cancer, 40% of women discontinue it because of side effects, notably depression and mood swings and those that continue are at risk of toxicity especially DVT, pulmonary emboli, endometrial hyperplasia and cancer. An agent that avoided systemic side effects and did not act as an estrogen on the endometrium would be superior.

 

  1. Cuzick, J. International Breast Cancer Intervention Study. A brief review of the International Breast Cancer Intervention Study (IBIS), the other current breast cancer prevention trials, and proposals for future trials. Annals of the New York Academy of Sciences. 2001; 949:123–133. 98.
  2. Altschuler, A., Somkin, C. P. Women’s decision making about whether or not to use breast cancer chemoprevention. Women & Health. 2005; 41(2):81–95. 99.
  3. Port, E. R., Montgomery, L. L., Heerdt, A. S., Borgen, P. I. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Annals of Surgical Oncology. 2001; 8(7):580–585.
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  5. Melnikow, J., Paterniti, D., Azari, R., et al. Preferences of Women Evaluating Risks of Tamoxifen (POWER) study of preferences for tamoxifen for breast cancer risk reduction. Cancer. 2005; 103(10):1996–2005.
  6. Ozanne, E. M., Klemp, J. R., Esserman, L. J. Breast cancer risk assessment and prevention: a framework for shared decision making consultations. Breast Journal. 2006; 12(2):103-113.
  7. Vogel, V. G., Costantino, J. P., Wickerham, D. L., et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. [See comment]. JAMA. 2006; 295(23):2727–2741.
  8. Cummings, S. R., Eckert, S., Krueger, K. A., et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999; 281(23):2189–2197.
  9. Vogel, V. G., Costantino, J. P., Wickerham, D. L., et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prevention Research. 2010; 3(6):696–706.