Women with an increased risk for breast- and ovarian cancer due to a genetic prediposition, after prophylactic adnectomy.
Conditions
Interventions
Patients will be randomized to receive either:
1. 0.625 mg conjugated estrogens and 5 mg medroxyprogesterone acetate continuously combined (arm1) or
2. 2.5 mg tibolone continuously (arm 2).
Trea
Sponsors
Initiator : Anca C. Ansink, MD, PHD, gynaecological oncologist
Dept. Obstetrics & Gynaecology, room A1-40
Erasmus MC- Daniel den Hoed Oncology Center
PO BOX 5201
3008 AE Rotterdam
The Netherlands
phone: +31 10 4391263
fax +31 10 4391011
E-mail: a.ansink@erasmusmc.nl
secundary sponsor:
NV Organon
Molenstraat 110
Postbus 20
5340BH Oss
The Netherlands
phone+ 31 412661222
fax. +31 412662617
Eligibility
Inclusion criteria
Inclusion criteria: 1. Prophylactic adnectomy not longer than five years ago, or scheduled to undergo prophylactic adnectomy within the next six months from randomization; 2. Age 25-50 years; 3. Premenopausal at the time of prophylactic adnectomy; 4. Either proven BRCA 1 or BRCA 2 mutation carrier or member of an HBOC-family (50% risk carrier); 5. Have intact breast tissue (and do not consider prophylactic mastectomy in the next year); 6. Informed consent has been obtained.
Exclusion criteria
Exclusion criteria: 1. HST/ OAC (oral anticonceptive) intake in the last three months; 2. History of breast cancer. Patients who have had adequately treated skin cancer (non-melanoma) or cervical carcinoma in situ are eligible. Furthermore, patients who have had another malignancy in the past, but have been disease free for more than 5 years are also eligible; 3. Abnormality on mammography that, according to the attending physician or radiologist, requires further diagnostic or therapeutic intervention; 4. Concomitant cardiovascular illness including: (recent) myocardial infarction, uncontrolled cardiac arrhytmias, angina pectoris, uncontrolled hypertension, and heart failure; 5. Current or history of deep venous thrombosis, thrombophlebitis, thromboembolic disease or suspicion of hereditary predisposition for developing venous thromboembolic disease or use of anticoagulation; 6. Abnormal endometrial thickness. For women having the ovaries still in situ, there is no maximum thickness. However, in women who were not exposed to endogenous or exogenous estrogens over the last three months, the double layer endometrial thickness should be less than 4 mm; 7. Hysterectomy; 8. Abnormal Pap smear; 9. Known or suspected hypersensitivity to estrogen and/or progesterone and/or tibolone; 10. Concomitant disease for which the use of exogenous hormonal steroids is contraindicated; 11. Use of one or more of the following drugs within the last two months: hepatic microsomal enzyme-inducing anticonvulsant drugs or drugs known to affect or interfere with the pharmacokinetics of steroids (e.g. hydantoins and/or barbiturates, such as phenobarbital, Bellergal®, rifampicin, griseofulvin, primidone or carbamazepine); 12. Use of investigational drugs within the past 6 months; 13. Alcohol and/or drug abuse within the last 3 months or any other condition that might result in premature discontinuation, according to the opinion of the investigator; 14. Abnormal laboratory values considered being clinically relevant by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Change in mammographic breast density; 2. Menopausal symptoms and sexuality. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Generic quality of life; 2. Compliance; 3. Bone density; 4. Incidence of benign breast disorders; 5. Incidence of breast carcinoma (in situ and invasive); 6. Incidence of other malignancies; 7. Incidence of gynecological disorders; 8. Incidence of cardiovascular disease; 9. Incidence of biliary surgery; 10. Incidence of bone fractures; 11. LDL and HDL levels; 12. Androgen levels. | — |
Contacts
Public ContactChristien C.M. Buis
Erasmus Medical Center, Department of Obstetrics and Gynaecology, P.O. Box 2040
Outcome results
None listed