Ductal Carcinoma in-situ is a noninvasive and completely curable form of breast cancer. The cancer cells are still inside the ducts of the breast and therefore cannot spread to other parts of the body. The goal of DCIS treatment is to prevent it from coming back in the same place in the breast. DCIS currently accounts for 25% of breast cancers in the United States.

Tamoxifen is an antiestrogen that blocks the actions of the female hormone, estrogen. Tamoxifen has significant benefits for women with DCIS. It reduces the risk of recurrence of the same cancer by a third, and prevents one-half of new breast cancers. This is important since women who have had DCIS have a 20% chance of developing a new breast cancer over the next 30 years. Tamoxifen halves this risk to about 10%.

DCIS treatment consists of surgery; if the surgical treatment is lumpectomy, it is followed by radiation to the breast. After this standard treatment, women whose DCIS is sensitive to estrogen (that is, the DCIS is positive for estrogen receptor (ER)) are usually advised to take tamoxifen as a pill by mouth for 5 years.

DCIS is a very slowly growing process, and many women wait several weeks for surgery for a variety of reasons (trips, family events, business reasons, scheduling reconstructive surgery.) Many studies have shown that a delay of 6-8 weeks has no effect on the chances of cure, and does not change any aspects of treatment.

Despite the benefits, undesirable side effects lead many women to decline tamoxifen treatment. These include hot flashes, vaginal dryness or discharge, and occasionally, leg cramps. More serious but rare side effects include the possibilty of blood clots and an increased risk for cancer of the uterus.

In addition, about a quarter of all women lack the enzymes which convert oral Tamoxifen into its active form, 4-OHT (4-hydroxttamoxifen). These women will not benefit from oral tamoxifen even if they take it.

To avoid the side effects of oral tamoxifen, we are testing the active form of tamoxifen, or 4-OHT. When applied as a gel to the skin of the breast, the 4-OHT reaches effective concentrations in the breast tissue, but the amount that gets into the circulation and therefore to the rest of the body is very small. Because of the circulating levels are low, hot flashes and other nuisance side effects should be far less of a problem. Similarly, the risk of uterine cancer will probably not be increased with 4-OHT gel. And because the liver is not exposed to 4-OHT when it is applied to the skin (which it is when tamoxifen is taken by mouth), the risk of blood clots should be avoided. Finally, because the active form is being used, and no activation by liver enzymes is required, all women who receive 4-OHT through the skin should benefit from it.