Breast lipids

F. Falck et al., Pesticides and Polychlorinated Biphenyl Residues in Human Breast Lipids and Their Relation to Breast Cancer, Arch. Environ. Health A7 (1992) 145-46. 

Falck, F., Ricci, A., Wolff, M. S., et al. 1992. Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Archives of Environmental Health 47 143-146. 

It has also been hypothesized that long-term hormone imbalance can induce cancers in endocrine-sensitive organs, such as gonads, adrenals, thyroid, prostate, and breast. Lipid-soluble compounds are of special concern because they are retained in the body, therefore causing a long-term effect. Some of these chemicals are known cytochrome P450 enzyme inducers, such as PCBs, DDT, and butylated hydro-xytoluene, and have been implicated in cancers in the adrenals, uterus, and thyroid. 

In postmenopausal women, recently reported evidence supporting the use of aromatase inhibitors in the adjuvant setting is intriguing and may usurp the role of tamoxifen. Three different approaches to therapy have been undertaken with these new agents (1) direct comparison with tamoxifen for adjuvant hormonal therapy, (2) sequential use after 5 years of adjuvant tamoxifen therapy, and (3) sequential use after 2 to 3 years of adjuvant tamoxifen. Based on results of several studies, it has been concluded that therapy for postmenopausal women with ER-positive breast cancer should include an aromatase inhibitor.27,47 It is still unclear if the aromatase inhibitor should be used instead of tamoxifen or sequentially after receiving tamoxifen for 2 to 5 years.27 Concerns surrounding loss of bone density, changes in blood lipids, and cardiac and vascular disease require further study.27... 

Jahan K., Paterson A. and Spickett C.M. (2004). Fatty acid composition, antioxidants and lipid oxidation in chicken breasts from different production regimes , International Journal of Food Science Technology, 39, 443 453. 

Numerous studies demonstrated that lipid peroxidation significantly decreased in cancer cells and tissues (Ref. [176] and references therein). It has been proposed that this can be a consequence of a decrease in the content of highly unsaturated fatty acids, the concentration of cytochrome p-450, and the contents of NADPH, SOD, and catalase in tumors. Cheeseman et al. [176] suggested that the reduction of lipid peroxidation in tumors may depend on both the expression of malignant transformation and cell division. It should be mentioned that Boyd and McGuire [177] demonstrated that there is a correlation between lipid peroxidation and breast cancer risk in premenopausal women. 

Tamoxifen is discussed in Chap. 61, Breast Cancer raloxifene is discussed in Chap. 3, Osteoporosis. Raloxifene decreases bone loss in recently menopausal women without affecting the endometrium and has estrogen-like actions on lipid metabolism. It may exacerbate vasomotor symptoms, and it increases the risk of venous thromboembolism and stroke. 

Strategies for reducing risk to the infant from drug transferred through breast milk include selection of medications for the mother that would be considered safe for use in the infant choosing medications with shorter half-lives selecting those that are more protein bound, have lower bio-availability, and have lower lipid solubility. 

Droloxifene (3-hydroxy-tamoxifen) behaves as an estrogen agonist in bone tissue and several lipid and coagulation markers in castrated rat models and does not show stimulation of the endometrial epithelium in preclinical studies (Ke et al. 1997). Endometrial stimulation has, however, been observed in clinical trials, which, together with the fact that as an estrogen agonist it is ten times less potent than tamoxifen in bone tissue and lipid metabolism (Hendrix et al. 2001) and that in a recent head-to-head comparison with tamoxifen droloxifene was demonstrated not to be superior in any parameter of breast cancer treatment efficacy (Buzdar et al. 2002), has resulted in cancellation of its clinical development. 

Love RR, Newcomb PA, Wiebe DA, Surawicz TS, Jordan VC, Carbone PP, DeMets DL (1990) Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J Natl Cancer Inst 82 1327-1332... 

Joensuu H, Holli K, Oksanen H, Valavaara R (2000) Serum lipid levels during and after adjuvant toremifene or tamoxifen therapy for breast cancer. Breast Cancer Res Treat 63 225-234... 

New SERMS are in different development stages. Lasoftmfene has been shown to have positive effects on bone and lipid metabolism without negative impact on uterine growth (Ke et al. 1998). There is a large-sample, prospective, randomized clinical trial in progress in which breast cancer, together with fracture prevention, is one of the main outcomes. 

In preclinical models, arzoxifene exerts an estrogen agonistic effect on bone and on the lipid profile and an estrogen antagonistic effect in breast and endometrium (Sato et al. 1998 Russo et al. 1990 Ma et al. 1998). Thus, in both the ovariectomized rat and the ovary-intact rat arzoxifene did not stimulate uterine weight gain (Russo et al. 1990). 

Cauley JA, Zmuda JM, Lui LY et al. (2003) Lipid lowering drug use and breast cancer innolder women a prospective study. J Womens Health 12(8) 749-756... 

The most recent National Human Adipose Tissue Survey did not detect endrin in adipose tissues from the general U.S. population (Stanley 1986). Endrin also was not detected in adipose breast tissue from breast cancer patients (n=5) or controls (n=5) in the United States (Djordjevic et al. 1994). A 1984 study based on autopsied adipose tissue from 141 cadavers from six Canadian Great Lakes municipalities showed no detectable concentrations of endrin (detection limit 2.4 ppb) (Williams et al. 1988). In a 1990-91 survey, only very low levels of endrin (average concentration 3.27 ng/g (ppb) range 0.23-8.56 ng/g [ppb] lipid)... 

In MDR cells, a significant fraction of P-gp is found associated with caveolin-rich membranes, and there is a substantial increase in the number of caveolae and caveolin-1 protein level. For example, both multidrug resistant human colon adenocarcinoma HT-29 cells and adriamycin-resistant breast adenocarcinoma MCF-7 cells display about a 12-fold increase in caveolin expression, which correlates with an approximate fivefold increase in morphologically identifiable caveolae [55], In addition, these cells exhibit increased amounts of phospholipase D and lipids such as cholesterol, glucosylceramide, and sphingomyelin [56, 57], Similarly, taxol-resistant A549 cells display both increased caveolin expression and caveolae numbers [58], While these correlations track with MDR, they do not suggest a simple mechanism for the role of... 

---