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
"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
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
The daily drug combination consists of 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
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.
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
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 Two women had withdrawn.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.