Breast density

Atkinson C, Warren RML, Sala E et al. Red clover-derived isoflavones and mammographic breast density a double-blind, randomized, placebo-controlled trial. Breast Cancer Res. 6, R170-R179, 2004. 

Another approach to the study of the effects of hormone replacement therapy on the breast is to examine breast density, using mammography and the Wolfe classification. In a randomized study of 166 menopausal women, using this technique, there was increased breast density after 6 months of treatment eight times more commonly in those who took estradiol and norethisterone acetate than in those who took tibolone (186). The significance of this increased density is not clear, but it should for the present be regarded as undesirable,... 

Lundstrom E, Christow A, Kersemaekers W, Svane G, Azavedo E, Soderqvist G, Mol-Arts M, Barkfeldt J, von Schoultz B. Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density. Am J Obstet Gynecol 2002 186(4) 717-22. 

Although raloxifene is not approved for prevention or treatment of breast cancer, a 4-year trial of raloxifene in women with osteoporosis (not at increased risk for breast cancer) showed a 76% risk reduction for estrogen-receptor-positive breast cancer" (relative risk 0.24, 95% Cl 0.13-0.44). Furthermore, the CORE trial, a study evaluating the efficacy of an additional 4 years of raloxifene therapy in women with osteoporosis, showed that the reduction in estrogen-receptor positive breast cancer incidence continues for up to 8 years" " (hazard ratio 0.24, 95% Cl 0.15-0.40) (see Table 80-9). Raloxifene does not increase breast density. A trial comparing raloxifene with tamoxifen is underway. 

A number of polymorphisms have been reported in the CYP19A1 gene. These have been studied in relationship to breast but without convincing relationships vide infra), also, there was no relationship with breast density . 

No changes in mammographic breast density, breast cell proliferation, or endometrial thickness were observed in postmenopausal women who consumed 40 mg daily of iso-propanolic extract of black cohosh for 6 months (Hirschberg etal. 2007). 

Hirschberg, A.L., M. Edlund, G. Svane, et al. 2007. An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women. Menopause 14(l) 89-96. 

No increase in mammographic breast density and no significant effects were observed on estradiol, follicle-stimulating hormone, or luteinizing hormone levels in a trial of women, ages 49 to 65, taking 44 mg red clover-derived iso-flavones daily for 1 year (Atkinson et al. 2004). 

In women aged 35 to 70 with at least one first-degree relative with breast cancer, administration of 40 mg of red clover isoflavones daily for 3 years did not result in any significant differences in breast density, endometrial thickness, serum cholesterol, follicle-stimulating hormone levels, or bone mineral density, as compared to placebo. In postmenopausal women, some differences in bone marker levels were seen between active and placebo groups at 6 and 12 months (Powles et al. 2008). 

Abebe, W. 2002. Herbal medication Potential for adverse interactions with analgesic drugs. /. Clin. Pharm. Ther. 27(6) 391-401. Atkinson, C., R.M. Warren, E. Sala, et al. 2004. Red-clover-derived isoflavones and mammographic breast density A doubleblind, randomized, placebo-controlled trial. Breast Cancer Res. 6(3) R170-R179. 

Metabolizing phenotypes in relation to mammographic breast density Women... 

Breast cancer Fetv RCTs, and none investigating breast cancer outcomes. Nipple aspirate fluid and other markers of estrogenic response Premenopausal women may have an estrogenic response to soy supplements. Mammographic breast density Mostly no effect of isoflavones but doubts remain in premenopausal women. Many animal studies have shown protective effects of soy, particularly when isoflavones introduced at an early life stage. However, increased tumorigenicity obsen/ed in response to isoflavones in some animal models. In vitro experiments suggest isoflavones induce a variety of cellular processes that inhibit breast cancer development, but depends on dose. Evidence insufficient. Inadvisable to increase soy isoflavone intake in women at risk of breast cancer, especially premenopausal women. 

Atkinson, C. and Bingham, S.A. 2002. Mammographic breast density as a biomaiker of effects of isoflavones on the female breast. Breast Cancer Res 4, 1-4. 

Hooper, L., Madhavan, G., Tice, J.A., Leinster, S.J., and Cassidy, A. 2010. Effects of isoflavones on breast density in pre- and post-menopausal women a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update. 

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