Let's start with breast cancer. Ductal Carcinoma In Situ, DCIS. Dr. Anton Titov, MD. It is earliest and localized form of breast cancer. But the decision-making on treatment is important. Dr. Anton Titov, MD. How to best treat localized breast cancer? Dr. Jack Cuzick, PhD. It is quite complex. Most women with DCIS have local breast-conserving therapy and radiation therapy. A minority of women with DCIS have recurrence despite those treatments. But the vast majority of patients with Ductal Carcinoma In Situ never recur. So DCIS treatment might be excessive. You have done major work in treatment decision-making in DCIS. What could you tell about your work? Dr. Anton Titov, MD. What the results of DCIS therapy have you obtained? It's certainly true that the treatment of DCIS is a major challenge. Dr. Jack Cuzick, PhD. There's really nothing in DCIS therapy that isn't being questioned at the moment. Some people even are concerned that it may not even be necessary to do any surgery. My personal view is that the lumpectomy to take out the bulk of the tumor is likely to be very effective. Surgery for DCIS has improved over the last decade or so. Surgeons take much greater attention for getting clear surgical resection margins. That had a major impact on the very low local recurrence rate. We see very little recurrence with DCIS. One of the bigger challenges is this. Who needs radiotherapy? At the moment there probably are far too many women getting radiotherapy for DCIS. It's almost a 100% in the United States and over 70% in the United Kingdom. Probably many of these women don't need radiotherapy. It's our challenge to figure out who does need radiotherapy for DICS. Our work has focused on endocrine therapy for DCIS. Dr. Jack Cuzick, PhD. We have done work both for the invasive cancers and also in the prevention setting. We do clinical trials in using tamoxifen or other aromatase inhibitors (letrozole, anastrozole). They could actually reduce recurrence rates in DCIS. The effects of tamoxifen are real. There have been two clinical trials looking at the effects of tamoxifen in DCIS. One clinical trial showed a clear benefit in local and contralateral breast cancer tumors. In our own clinical trial, results were not so positive for local recurrence for DCIS. It did show an effect on contralateral tumors. So I think radiotherapy is still a bit of an option. But for women that tolerated endocrine therapy well, aromatase inhibitors (letrozole, anastrozole) and tamoxifen prevent recurrences. That's the majority of women with DCIS. These women are at very high risk of new breast tumors in the opposite breast. So it's not only recurrence. It's actually preventive therapy for new breast cancers. Dr. Jack Cuzick, PhD. The effects in DCIS prevention are not so striking as they are with invasive cancer. Some women that do have side effects from hormonal therapy for DCIS. Some women have difficulty tolerating tamoxifen and other hormonal medications. For such patients it's not unreasonable not to take hormonal therapy for DCIS. Aromatase inhibitors (letrozole, anastrozole) and tamoxifen are almost certainly only appropriate for estrogen receptor-positive DCIS. Until recently in many places receptor status in DCIS is not routinely measured. So there are a range of issues there. Other issues relate to other markers. 40% of DCIS tumors are HER2 positive. That may be important as well for determining how much hormonal therapy should be given.