The hormone replacement therapy opposed to low dose tamoxifen (HOT) study: safety data from an ongoing phase III trial

Abstract

1514 Background: Primary prevention trials have shown that tamoxifen (T) lowers ER+ breast cancer (BC) incidence by 48%. While the IBIS I update showed mixed findings, the Italian trial showed an interesting positive risk/benefit ratio in T and hormone replacement therapy (HRT) users: fewer BC, endometrial cancer comparable to placebo, and no cardiovascular diseases (CVD) excess. In a phase II study, low dose T and HRT showed a safe gynecological profile and did not increase menopausal symptoms. Moreover low dose T maintains the same antiproliferative effects as the standard dose. To improve BC prevention and quality of life (QoL) in menopausal women we started a multicentric, phase III trial of low dose T in HRT users. Methods: current or de novo HRT users are randomized to T 5 mg/day or placebo for 5 yrs. The primary aim is the reduction of invasive or in situ BC. Secondary aims are: safety, gene polymorphisms (SNPs) correlated to BC risk and T activity. In a subgroup transvaginal ultrasound (TvUS) and endometrial biopsy is being performed after 3 years of treatment to monitor endometrial effects. Results: as of December 31 2006, 1870 women were enrolled, of which 21% were hysterectomized. Median age is 53 years (33–72), BMI is <25 in 66%, =25<30 in 26%, >30 in 8%. Current or de novo users are 80% and 20%. 84% participants have at least one follow-up visit. 128 subjects performed already the 3 years TvUS and endometrial biopsy: so far no atypical hyperplasia or cancer was found. A modest increase of menopausal symptoms was observed (hot flashes 42% vs 52%, night sweating 39% vs 44%). Drop-outs are 23%, of which 13% due to AE including: 21 cancers (12 invasive BC, 1 DCIS), 13 CVD (3 VTE), 9 gynecological (5 endometrial polyps). Conclusions: combination of low dose T and HRT has reasonable safety profile, we have reached almost 1,900 women on study and AE rate is very low. These unblinded findings support the safety of the association of HRT and T. No significant financial relationships to disclose.