Chemoprevention of cancer is an important area. Chemoprevention means the use of pharmaceuticals in cancer prevention. Dr. Anton Titov, MD. Breast cancer is the most common cancer in women. There are some strategies for chemoprevention of breast cancer. You have done seminal work in this cancer prevention area. The results from clinical trials demonstrate chemoprevention of breast cancer is very effective. Dr. Anton Titov, MD. What are the strategies to prevent breast cancer by medications? Dr. Jack Cuzick, PhD. I think the breast cancer is one of these unique examples. We have learned a lot about treating breast cancer with hormonal therapies. You are treating cancer arising in one breast. Then you can observe in that same woman whether new cancer arises in the opposite side, in another breast. This was originally done for tamoxifen. I think it was as early as 1985. Then we reported preventive effects of tamoxifen in the early clinical trials. Tamoxifen use to treat breast cancer was producing 50% reductions in contralateral tumors. Now that's held up in terms of estrogen receptor-positive cancers. In the prevention clinical trials you get about 50% reduction of breast cancer in contralateral breast. But there's no real impact of tamoxifen on estrogen receptor-negative cancer. So the overall benefit of tamoxifen is about 35% reduction of breast cancer. Dr. Jack Cuzick, PhD. More recently, for postmenopausal breast cancer, new cancer-preventing medications appeared. The aromatase inhibitors have been shown to be more effective than tamoxifen in therapy of breast cancer. Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin). They prevent recurrence and deaths from breast cancer. In those clinical trials we have been able to look at new contralateral breast tumors. We have seen bigger preventive effect on contralateral breast tumors with the aromatase inhibitors than with tamoxifen. Aromatase inhibitors are anastrozole, letrozole or exemestane. So this led us and others to do clinical trials of aromatase inhibitors for cancer prevention only in postmenopausal women. Dr. Jack Cuzick, PhD. Yes, the cancer-preventive effect sizes are larger than you see for tamoxifen. Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin). have breast cancer-preventive effects on the order of 50% to 70% reduction in cancer recurrence. Dr. Anton Titov, MD. In primary prevention? In primary prevention of breast cancer. Again, the preventive effects are only on estrogen receptor-positive cancers. But the cancer-preventing effects of aromatase inhibitors are really quite striking. So we're quite excited about that. There have been no direct prevention clinical trials comparing tamoxifen vs anastrozole. Those clinical trials will have to be enormous to get a clear answer. But we are getting clear indirect answers that anastrozole is probably more effective. Dr. Jack Cuzick, PhD. We are also see that supported by contralateral breast tumors in the breast cancer treatment clinical trials. There are clinical trials ongoing, and more data coming in. It is there a potential recommendation for postmenopausal women to take aromatase inhibitors. It will happen maybe sometime in the future. Dr. Anton Titov, MD. Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin) work for certain subgroups of women perhaps? My expectation is that that there will be recommendation to use aromatase inhibitors for breast cancer prevention. The NICE committee in the UK has now recommended tamoxifen and raloxifene for prevention of breast cancer in high-risk breast women. Dr. Jack Cuzick, PhD. Those recommendations were made before aromatase inhibitor prevention data were available. The committees are currently meeting right to consider whether they should recommend aromatase inhibitors for breast cancer prevention. Dr. Anton Titov, MD. These medications are anastrozole, letrozole or exemestane. I think the evidence is very strong. I would be hopeful that anastrozole would be added to the armamentarium of what we can do to prevent breast cancer. Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin)