title: The Royal Marsden Hospital pilot tamoxifen chemoprevention trial.
abstract: A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been undertaken in order to evaluate the problems of accrual, acute symptomatic toxicity, compliance, and safety as a basis for subsequent large national multicentre trials designed to test whether tamoxifen can chemoprevent breast cancer. From October 1986 until June 1993, 2012 healthy women with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxifen 20 mgs/day or placebo for up to 8 years if possible. Accrual remained high in spite of extensive informed consent regarding potential risk. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medication at 5 years. There was a significant increase in hot flushes (34% versus 20%) mostly in premenopausal women (p < 0.005), vaginal discharge (16% versus 4%, p < 0.005), and menstrual irregularities (14% versus 9%, p < 0.005). The requirements for hormone replacement therapy for women on tamoxifen or placebo were the same. Safety monitoring indicates no adverse anti oestrogenic effects of tamoxifen. There was no obvious effect of tamoxifen on bone mineral densities (single photon radial absorption). The fibrinogen and antithrombin III were both lowered, resulting in no observed detrimental effect on the ratio of these clotting factors. There was a significant reduction in the serum cholesterol maintained out to 5 years. Annual pelvic assessment using transvaginal ultrasound indicates an increased incidence of uterine fibromata and benign ovarian cysts.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Breast Unit, Royal Marsden Hospital, London, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.forename: A L
authors.initials: AL
authors.lastname: Jones
authors.forename: S E
authors.initials: SE
authors.lastname: Ashley
authors.forename: M E
authors.initials: ME
authors.lastname: O'Brien
authors.forename: V A
authors.initials: VA
authors.lastname: Tidy
authors.forename: J
authors.initials: J
authors.lastname: Treleavan
authors.forename: D
authors.initials: D
authors.lastname: Cosgrove
authors.forename: A G
authors.initials: AG
authors.lastname: Nash
authors.forename: N
authors.initials: N
authors.lastname: Sacks
authors.forename: M
authors.initials: M
authors.lastname: Baum
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis; D015519:Bone Density; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D008593:Menopause; D008597:Menstrual Cycle; D008875:Middle Aged; D009679:Nuclear Family; D010053:Ovary / Q000000981:diagnostic imaging; D010349:Patient Compliance; D010865:Pilot Projects; D010919:Placebos; D012307:Risk Factors; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D016312:Treatment Refusal; D014463:Ultrasonography
chemical_list: D016588:Anticarcinogenic Agents; D010919:Placebos; D013629:Tamoxifen; D000990:Antithrombin III; D005340:Fibrinogen; D002784:Cholesterol