We did a phase III trial of low dose tamoxifen which is an anti-oestrogen to prevent recurrence in women who had a non-invasive breast cancer which can be either an atypical ductal hyperplasia or a lobular or ductal carcinoma in situ. These forms are very common today with the introduction of screening mammography – at least 20% of all breast neoplasms are intraepithelial neoplasia.
We found a 50% reduction in the recurrence in the low dose tamoxifen arm compared with placebo which is the same effect that we found in the past with 20mg which is the standard dose. We used, however, 5mg per day which is a lower dose which is associated with fewer side effects. Our side effects with tamoxifen typically are endometrial cancer, deep vein thrombosis, menopausal symptoms such as hot flushes, vaginal dryness, pain during intercourse and others. In this trial we showed a lowering of these serious adverse events – we just noted one case of stage 1 endometrial cancer, we would predict nearly 3 with a full dose. We saw one case each of venous thromboembolism, both in the tamoxifen arm and the placebo arm whereas we would have predicted 2.5 with a full dose. Perhaps more importantly we saw no difference in menopausal symptoms, there was in fact a slight borderline significant increase in the number of hot flushes per day which resulted in less than one extra hot flush per day compared with placebo, no increase in the intensity of the hot flushes and, perhaps more importantly, no increase in pain during intercourse or vaginal dryness. Finally, we noted no increase in arthralgias or musculoskeletal pain which are frequently associated with aromatase inhibitor treatment.
What are the next steps for this study?
We saw a very intriguing 75% reduction of contralateral breast cancer which, of course, opens the doors for a primary prevention trial in healthy at risk women because the side effects of tamoxifen have prevented its broad use in prevention despite strong evidence of efficacy but the side effects preclude its use. So we hope that with the lower dose more women will take this drug for primary prevention, especially those who are at high risk, including perhaps the women with a BRCA mutation.
Have you got anything to add?
The study was supported by the government, the Italian government, and two charities – the Italian Association for Cancer Research and the Italian League Against Cancer. We are indebted to these associations, institutions, for supporting a study aimed at maintaining a fair, equitable and affordable medicine.