Table 1 Summary of the main published trials on low dose tamoxifen
From: Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug
Study | Treatment | Number of patients | Population | Primary endpoint | Comment |
|---|---|---|---|---|---|
Breuer et al. 1998 [80] | TAM 20 mg/day (91%) TAM 10 mg/day (9%) | 1,385 matched with 5,196 controls | Women 65 years and older | Bone fracture | Although standard treatment of 20 mg TAM daily offers no apparent protection against bone fracture in older nursing home residents, a daily 10 mg dose seems to be protective |
Decensi et al. 1998 [11] | Placebo TAM 20 mg/day TAM 10 mg/day TAM 10 mg alternate days | 127 | Healthy women Hysterectomized 35 to 70 years | Total cholesterol (primary) Surrogate markers of cardiovascular disease, IGF-I | Up to a 75% reduction in the conventional dose of TAM (that is, 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular disease |
de Lima et al. 2003 [25] | Placebo TAM 5 mg/day TAM 10 mg/day TAM 20 mg/day | 56 | Premenopausal women with a diagnosis of fibroadenoma of the breast | ER alpha PgR Ki-67 apoptotic bodies and mitotic index | Excisional biopsy was performed on the 50th day of therapy. Normal breast tissue samples were collected during surgery. Differences in the expression of ERa, PgR, Ki-67, apoptotic bodies and mitotic index between the different groups after treatment can be seen on the normal breast tissue |
Decensi et al. 2003 [26] Decensi et al. 2010 (f-up) [30] | TAM 1 mg/day TAM 5 mg/day TAM 20 mg/day | 120 | ER+, BC patients 4 weeks before surgery | Ki-67 modulation | Ki-67 expression decreased to a similar degree among the three TAM dose groups. Ki-67 expression after short-term TAM is a good predictor of recurrence-free survival and overall survival |
Decensi et al. 2007 [44] | TAM 1 mg/day TAM 5 mg/day TAM 10 mg/week Placebo | 210 | Current or de novo HRT users | IGF-I | IGF-I declined in all TAM arms (P = 0.005), with a greater change on 5 mg/day. Tamoxifen did not increase endometrial Ki-67 expression |
Decensi et al. 2009 [35] | TAM 5 mg/day FEN 200 mg/day TAM + FEN Placebo | 235 | Premenopausal women pT1mic/pT1a BC; OR Intraepithelial neoplasia; OR Gail risk at five years ≥1.3% | Plasma IGF-I Mammographic density; uterine effects; breast neoplastic events after 5.5 years | Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose TAM plus FEN did not reduce breast neoplastic events |
Bonanni et al. 2009 [41] | ANA 1 mg/day TAM 10 mg/week ANA + TAM | 75 | Postmenopausal women with previous breast intraepithelial neoplasia | Plasma drug concentrations Biomarker modulation | The addition of weekly TAM administration did not impair anastrozole bioavailability and modulated favorably its safety profile |
Guerrieri Gonzaga et al. 2010 [49] | TAM 20 mg/week TAM 5 mg/day | 680 | Women with previous DIN | Second primary breast cancer (in situ or invasive) | High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN, and low-dose TAM appears to be an active treatment. Women with low-expression ER or PgR DIN do not seem to benefit from TAM |