In women at increased risk of invasive breast cancer, risk-reducing treatment with selective oestrogen receptor modulators (SERMs), such as tamoxifen or raloxifene, reduces the risk of oestrogen receptor-positive breast cancer. Although women with LCIS comprise a relatively small proportion of subjects in the relevant clinical trials, the extent of risk reduction with SERMs is similar in women at increased risk due to LCIS compared to women at increased risk for other reasons such as family history (risk reductions of 56% and 49%, respectively).11 Tamoxifen has been shown to reduce the risk of breast cancer for up to 20 years, even when taken for only five years.12 In post-menopausal women at increased risk of breast cancer, risk-reducing treatment with the aromatase inhibitors (AIs) anastrozole or exemestane has been shown to reduce the risk of invasive breast cancer.13, 14 Treatment with a SERM or an AI has been shown to halve the cumulative invasive breast cancer rate in women with LCIS. 6
Whilst risk-reducing medication is effective at reducing invasive breast cancer incidence in women at higher risk, it is unclear if these effects impact on overall survival. Furthermore, the potential benefits of risk-reducing medication need to be weighed against potential adverse effects.6 For pre-menopausal women, tamoxifen increases the risk of thromboembolic events such as deep vein thrombosis, although the absolute risk is low and similar to the risk associated with use of oral contraceptives.15, 16 For post-menopausal women, tamoxifen increases the risk of thromboembolic events, endometrial cancer, and cataracts, although the additional absolute risk of serious complications is low.17, 18 The AIs have a different side-effect profile compared to the SERMs. Anastrozole and exemestane are associated with a loss of bone mineral density and hypertension (but not thromboembolic or cardiovascular events), and are not associated with increased risk of other cancers.13, 14, 19
Risk-reducing medication for the prevention of invasive breast cancer is a management option for women with a diagnosis of LCIS. The decision to use medication for risk reduction should consider an individual woman’s overall clinical profile.