Effect of tamoxifen at low doses on ultrasensitive C-reactive protein in healthy women

Abstract

Summary. The use of tamoxifen as a breast cancer preventive agent may be contraindicated by an increased risk of endometrial cancer and venous thromboembolic events, particularly in postmenopausal women. Since these estrogenic effects may be doserelated, a dose reduction may reduce toxicity. We have recently shown a comparable activity of lower doses of tamoxifen on putative surrogate biomarkers of cardiovascular disease and breast cancer. To provide further insight into the effect of tamoxifen at low doses on the cardiovascular system, we compared the effect of three different doses on circulating levels of C-reactive protein (CRP), an independent risk marker for cardiovascular disease (CVD), which was lowered by tamoxifen at the standard dose of 20 mg day À1 in previous studies. We compared the changes in CRP after 2 months of either placebo (n 24), or tamoxifen 10 mg alternate daily (n 26), or 10 mg day À1 (n 22), or 20 mg day À1 (n 19) in healthy women aged 35±70 years. The median percent change was À2.2% (95% CI, À23.3 to 42.8) with placebo, À39.1 (95% CI, À59.9 to À28.7) with 10 mg alternate daily, À56.9% (95% CI, À68.6 to À38.4) with 10 mg day À1 and À42.9% (95% CI, À62.6 to 1.6) with 20 mg day À1 (P 0.291 for the linear dose±response trend). Similar results were obtained when the data were classi®ed according to blood tamoxifen concentrations, with a median reduction of 47% (95% CI, 65.5±36.3) for women with low tamoxifen concentrations (< 30 ng mL À1 ). We conclude that tamoxifen at low doses is able to lower ultrasensitive CRP and that this might be associated with a bene®cial effect on CVD.

Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors

“…Intervention studies have shown that alpha-tocopherol, a form of vitamin E with purported antiinflammatory properties [43], reduces serum concentrations of CRP in healthy individuals [44], type 2 diabetics [44,45], and smokers with acute coronary syndromes [46]. Intervention studies also suggest that low doses of tamoxifen decrease serum CRP concentrations in healthy women [47,48] and in women with ER positive breast tumors [71], consistent with the observed association in this study.…”

Lasofoxifene and Cardiovascular Events in Postmenopausal Women With Osteoporosis

“…9 Tamoxifen, 2,15 raloxifene, 3,4 and lasofoxifene 3,11 all lower LDL cholesterol (with no effect on HDL cholesterol); the magnitude of the reduction appears greatest with lasofoxifene. Lasofoxifene 11,16 and tamoxifen, 17 but not raloxifene, 18 reduce levels of C-reactive protein, and all 3 agents lower fibrinogen levels. 4,15,16 Thus, it is unlikely that the different …”

Tamoxifen Alters the Plasma Concentration of Molecules Associated with Cardiovascular Risk in Women with Breast Cancer Undergoing Chemotherapy

“…Tamoxifen, a selective modulator of ER, acts as an estrogen antagonist in breast tissue [15] and an agonist in other tissues, such as in the cardiovascular system [16]. Tamoxifen is known to be cardioprotective by reducing blood levels of total cholesterol, low density lipoproteins (LDLs) [10,17], and CRP in healthy women [18] and in women with estrogen-dependent breast cancers [19]. It has been observed that the use of tamoxifen also increases apolipoprotein A-1 (Apo-A) and reduces apolipoprotein B-100 (Apo-B) levels; these markers are considered to be more reliable markers of CVD risk than high density lipoprotein (HDL) and LDL cholesterol levels [20].…”