Breast Cancer: Tamoxifen Metabolite Promising

In the first human experience with a drug that is the main metabolite of tamoxifen, promising responses were observed in woman diagnosed with aromatase inhibitor resistant, metastatic breast cancer, researchers said here.

In a dose-ranging Phase 1 trial that included 22 women, two partial responses were observed and nine women achieved disease stabilization on seven different doses of endoxifen, said Matthew Goetz, MD, deputy director of the Mayo Clinic Breast Cancer Specialized Program of Research Excellence (SPORE), Rochester, Minn.

Ten women progressed while on endoxifen; one woman was not evaluable, Goetz said in his poster discussion sessions at the annual San Antonio Breast Cancer Symposium.

He said that low concentrations of endoxifen were associated with poorer outcomes in both breast cancer patients and in animal models.

He noted that in an animal model of a letrozole resistant xenograft, endoxifen appeared superior to tamoxifen, exemestane and exemestane plus everolimus (RAD001). "The reasons for the superior antitumor activity of endoxifen appears to be complex, and related to the fact that endoxifen is a more potent anti-estrogen, does not activate critical oncogenes involved in nongenomic signaling and may inhibit other kinases."

The women in the trial were treated at doses from 20 mg to 160 mg. One dose limiting toxicity – a pulmonary embolus – was observed in one patient at the 60 mg dose. The most common grade 2 side effect seen was hot flashes. There was no evidence of eye toxicity on serial dilated eye exams.

When it comes to breast cancer, it’s important to understand that getting regular mammogram screenings is NOT going to prevent anything. In fact, mammography, which employs radiation, can increase your risk since ionizing radiation itself causes cancer... As Dr. Horner writes in her book:

“A European study published in 2012 found that when those who have the genetic predisposition for breast cancer (BRCA1 or BRCA2 gene mutation) are exposed to any diagnostic radiation before age thirty, their risk of breast cancer increases by 90 percent.

The study also found that a history of mammography before age thirty raised the risk by 43 percent. In fact, even one mammogram before the age of thirty for those with the BRCA1 gene mutation was associated with an increased risk.

A newer type of mammogram touted to be much better at detecting breast cancers, called tomosynthesis, takes a 3-D image of the breast. You definitely want to avoid this type of mammogram because it uses three times more radiation than the standard type!”

Furthermore, mammograms:

Are incorrect 80 percent of the time (providing a false negative or false positive)
Use compression, which can damage breast tissue or potentially spread cancer