Positive Health Online

Abstract

JOHANSSON and COLLEAGUES,  (1)Division of Cancer Prevention and Genetics, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy, harriet.johansson@ieo.it assessed the effect of tamoxifen and fenretinide on sex hormones, sex  hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events.

Background

Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. The authors aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events.

Methodology

In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. The authors measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models.

Results

Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile.

Conclusion

The authors conclude that low-dose tamoxifen or fenretinide exhibits favourable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in pre-menopause. Notably, SHBG levels were inversely associated with breast neoplastic events.

References

Johansson H(1), Bonanni B, Gandini S, Guerrieri-Gonzaga A, Cazzaniga M, Serrano D, Macis D, Puccio A, Sandri MT, Gulisano M, Formelli F, Decensi A. Circulating hormones and breast cancer risk in premenopausal women: a randomized  trial of low-dose tamoxifen and fenretinide.  Breast Cancer Res Treat. Dec 2013. 142(3):569-78. doi: 10.1007/s10549-013-2768-7.  Nov 17 Epub 2013.