University of Colorado Denver
Area of Focus: Treatment and Tumor Biology
Co-Investigator: Carol Sartorius, PhD, University of Colorado Anschutz Medical Campus, Denver, Colorado
- Seeking to identify new treatment approaches for recurrent luminal breast cancers.
- Laboratory studies are conducted to explore the potential benefit of progestin-based therapies for patients whose breast cancer has come back.
- This research will help to determine whether drugs used for birth control may provide a less-toxic approach for women with estrogen-driven breast cancers.
Most breast cancers require estrogen to grow. These are treatable and often curable with anti-estrogen therapies, but for some women the breast cancer will come back, sometime many years later. When breast cancers recur, they are often resistant to the treatment that the patient initially received. The standard therapy then is a combination treatment that works well for many, but not all women. Dr. Horwitz in collaboration with Dr. Carol Sartorius is conducting studies to test an alternative and less toxic approach for women with recurrent estrogen-drive breast cancers.
Full Research Summary
Approximately 75 percent of all breast cancers fall into the luminal classification. These tumors are characterized by having both estrogen and progesterone receptors. Most patients with luminal breast cancer have a very good five-year prognosis when treated with anti-estrogen therapies, like the anti estrogen tamoxifen or aromatase inhibitor after breast cancer surgery. While these therapies can be curative, luminal breast cancer survivors face an unsettling lifelong risk of recurrence.
Current treatments for recurrent breast cancer include an aromatase inhibitor plus newer drugs called CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib). These drugs prolong survival, but are not curative, have serious side effects, and not all patients receive benefit.
Luminal tumors also have progesterone receptors (PRs), which are natural inhibitors of estrogen receptors. Dr. Sartorius and her team propose that progestin-based therapies may be a less-toxic option for some patients with luminal disease.
Progestin-based birth control is widely used for healthy women. However, the role of progestin as a breast cancer treatment has been controversial, with both “beneficial” and “harmful” effects widely reported. This year, the research team will conduct laboratory studies to shed new light on the controversy so that patients with luminal breast cancer may benefit from these drugs.
Kathryn B. Horwitz, PhD joined the faculty at the University of Colorado after undergraduate studies at Barnard College, graduate studies at the UT Southwestern Medical School and postdoctoral work at UT San Antonio. Research in her laboratory is both basic and translational. It focuses on the role of women’s hormones – estradiol and progesterone – and their receptors, on luminal breast cancer cell heterogeneity, growth, treatment, metastasis and stem cells. Her lab has extensive expertise in molecular and tumor-cell biology, using in vitro and in vivo models and clinical samples. Long-term goals are to improve the strategies and outcomes of therapies for luminal disease. Research topics include: transcriptional mechanisms of progesterone receptors; epigenetic and post-transcriptional receptor modifications and signaling cross-talk; hormones in cancer growth; mechanisms of resistance to endocrine therapies; hormones and regulation of breast cancer stem cells; intratumoral cell heterogeneity in luminal disease; hormonal regulation of metastasis and the stromal microenvironment; development of new breast cancer models, and translation of laboratory findings into clinical practice. She has mentored numerous trainees who hold senior faculty posts at many US medical centers. She is a well-known national and international scholar, has served on multiple society boards, study sections and editorial boards, was elected President of the Endocrine Society, received its Fred Conrad Koch Award for exceptional contributions to endocrinology, and recently received the National Cancer Institute’s Rosalind E. Franklin Award for commitment to cancer research.