The Prevention of Breast CancerThe first human evidence that drug treatment might reduce the incidence of breast cancer was reported in 19851, where it was found that use of tamoxifen in a trial of women with breast cancer to reduce recurrence of existing tumours also had a major impact on new tumours in the opposite breast, reducing them from 10 to 3. That observation has subsequently been confirmed in several other adjuvant trials and an overview of all such trials indicates that after an average of about 8 years of follow up, 5 years of tamoxifen reduced new contralateral tumours by 39%, with similar effects in years 0-5 and 5-10 in women with oestrogen receptor positive or unknown primary tumours2. These observations and positive results from animal studies3, led to the evaluation of 5 years of tamoxifen in women without breast cancer, but at high risk in 4 large trials. A recent overview4 indicates a 33% reduction in all breast cancer after a 10 years follow up, with a larger reduction in years 0-5 (48%), when treatment was given, and a continuing (22%) effect in years 5-10. Reductions were seen for oestrogen receptor positive invasive cancer (44%) and DCIS (28%), but no effect was seen for both oestrogen receptor negative invasive cancer, where in fact a non-significant 13% (P=0.4) increase was observed. Somewhat larger effects were seen for these other selective estrogen receptor modulators (SERMs) – raloxifene, lasofoxifene and arzoxifene – in trials of osteoporotic women, where the primary endpoint was fracture reduction4. A subsequent head-to-head trial of raloxifene vs tamoxifen, showed tamoxifen to be about 20% more effective, but raloxifene had fewer side effects5. Lasofoxifene not only showed benefits for breast cancer reduction but also reduced fracture rates and heart disease6, and this multi-dimensional set of benefits makes it an attractive candidate for prevention. (more…)
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