SAN ANTONIOA pharmaceutical alternative to prophylactic oophorectomy as a means of inducing menopause and reducing the likelihood of breast cancer in young women at high genetic risk is under investigation at the City of Hope National Medical Center.
The advantage of a drug combination over oophorectomy for use in this high-risk population is its reversibility. If effective, young women could reduce their risk of breast cancer without losing their ability to have children.
"The regimen produces a medical menopause," said Jeffrey N. Weitzel, MD, director, Department of Clinical Cancer Genetics, City of Hope National Medical Center, at the 23rd Annual San Antonio Breast Cancer Symposium.
In this phase IB clinical trial, women at high risk of breast cancer (many on the basis of a BRCA gene mutation), ranging in age from 21 to 41 years, are being given a hormonal drug combination self-administered as a nasal spray.
The daily drug combination consists of deslorelin(Drug information on deslorelin), a gonadotropin-releasing hormone agonist (GnRHa) (1 mg/100 µL), plus very low doses of add-back steroids17-beta-estradiol (0.3 mg/100 µL) and testosterone (0.275 mg/100 µL). Intermittent oral medroxyprogesterone(Drug information on medroxyprogesterone) acetate (10 mg/d for 14 days at the end of each 12-week cycle) is given to protect the endometrium.
The regimen exposes the body to a low level of estrogen, the same amount as does the menstrual cycle at its lowest point each month, Dr. Weitzel said.
He noted that another GnRHa, leu-prolide acetate (Lupron), has also been studied as a risk-reducing agent, but it has the disadvantage that it must be administered as an intramuscular injection.
The primary study endpoint is a reduction in breast density, Dr. Weitzel said, which serves as an endpoint for reduced breast cancer risk and also en-hances mammography screening, which could lead to increased detection of asymptomatic breast cancers.
Three women had completed the 1-year study and three women were still enrolled at the time of the presentation. Two women had withdrawn. Preliminary findings showed that the regimen decreased breast density (see Figure). This alone makes the drug combination valuable, he said, because a less dense breast is easier to read on mammography.
The return of menses after completion of the study was relatively prompt, 42 and 48 days for the two patients for whom results were available. (He noted that 62 patients on a similar regimen for treatment of uterine fibroids had a return of menses at a mean of 29.9 days.) Bone density remained within normal limits, and quality of life measures showed no significant changes. A larger randomized study is planned.