Investigating a Solution for Sexually Active Breast Cancer Survivors

Research seeks to determine the suitability of tamoxifen vaginal inserts as an option following treatment

Innovations in Obstetrics & Gynecology | Winter 2021

 James Liu, MD

Breast cancer patients may enter early menopause following treatment — or they may already be menopausal at the time of diagnosis and treatment. Many of these women are still sexually active, but they struggle with discomfort due to vulvovaginal atrophy.

While women without breast cancer can use estrogen-based solutions, the majority of breast cancer patients and survivors are estrogen receptor-positive and cannot use these products due to concerns of stimulation in breast tissue, according to James H. Liu, MD, Chair of the Department of Obstetrics and Gynecology at University Hospitals Cleveland Medical Center and Arthur H. Bill Professor and Chair of Reproductive Biology at Case Western Reserve University School of Medicine.

“This is an unmet need,” Dr. Liu says. “There is no one particular product that targets this population.”

He is conducting research at UH to determine the suitability of tamoxifen vaginal inserts as an option for women who want to remain sexually active following breast cancer treatment.

“The idea of how these medications or hormones affect different components of the reproductive system is an area I have been working on for decades,” says Dr. Liu, who has secured patents on vaginal drug delivery over the course of his research career.

TAMOXIFEN VAGINAL INSERT

Selective estrogen receptor modulators (SERMs) are used to treat breast cancer. The SERM tamoxifen has long been a mainstay in breast cancer treatment, being used in women at high-risk of breast cancer and in women who have had breast cancer to reduce the likelihood of breast cancer reoccurring.

Tamoxifen has been on the market for years, but Dr. Liu and his team at UH are doing research to help reengineer the product into an application that can help improve the quality of life for breast cancer patients and survivors.

They are focusing on how the compound behaves differently in the vagina than in breast tissue, Dr. Liu says. “This compound acts like an estrogen in the vagina and the uterus, as opposed to an anti-estrogen in the breast.”

This opens the door to using tamoxifen as a solution to vaginal discomfort and dryness in breast cancer patients and survivors.

“The company that I am working with is trying to develop a capsule or caplet product that melts at body temperature and uses tamoxifen locally to stimulate regrowth of the tissues that are thinned by the lack of estrogen,” he says. “It makes intercourse more comfortable."

PHASE I STUDY WITH DARÉ BIOSCIENCE

Dr. Liu is working with Daré Bioscience on a Phase I study to determine the safety of tamoxifen vaginal inserts for women with breast cancer. The estrogenic effects of tamoxifen taken orally to prevent breast cancer or to suppress a reoccurrence of the cancer can result in a thickening of the uterine lining.

“Endometrial cancers have been reported with tamoxifen taken orally,” he says. “So, our hypothesis or goal is to demonstrate no stimulation to the uterus.”

Dr. Liu is still working on the pharmacokinetics to determine the optimum dosing for the insert. The insert holds such promise for women with breast cancer because of the way it is absorbed in the body.

“The circulation system and lymphatic system are such that the outer and lower one third of the vagina does not seem to demonstrate delivery to the uterus or the blood stream,” he says. “It would not be stimulatory to the uterus to breast, yet would have estrogenic effects on the lower vagina.”

Daré Bioscience has developed some prototypes and done some testing, but the research team is working to obtain National Institutes of Health funding through the Small Business Innovation Research program. For this study, UH and its partner Case Western Reserve University are working jointly to handle the funding and support the research.

Dr. Liu is working with Corinne Bazella, MD, Obstetrics and Gynecologist, UH Cleveland Medical Center and Associate Professor at the School of Medicine, who focuses on menopause care. Once the study gets funded, he hopes to bring on board more doctors who work with breast cancer patients.

He hopes to be able to take the next step and conduct a Phase II study, aimed at developing the insert product and sending it to the Food & Drug Administration for review.

To learn more about the research, call the UH MacDonald Women’s Hospital clinical trials team at 440-995-3811.