High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women

Abstract

High-density lipoprotein-cholesterol (HDL-C) may influence the proliferation of breast tumor cells, but it is unclear whether low HDL-C levels, alone or in combination with cyclic estrogen and progesterone, are associated with mammographic density, a strong predictor of breast cancer development. Fasting morning serum concentrations of HDL-C were assessed in 202 premenopausal women, 25 to 35 years of age, participating in the Norwegian Energy Balance and Breast Cancer Aspects (EBBA) I study. Estrogen and progesterone were measured both in serum, and daily in saliva, throughout an entire menstrual cycle. Absolute and percent mammographic density was assessed by a computer-assisted method (Madena), from digitized mammograms (days 7-12). Multivariable models were used to study the associations between HDL-C, estrogen and progesterone, and mammographic density phenotypes. We observed a positive association between HDL-C and percent mammographic density after adjustments (P ¼ 0.030). When combining HDL-C, estradiol, and progesterone, we observed among women with low HDL-C (<1.39 mmol/L), a linear association between salivary 17b-estradiol, progesterone, and percent and absolute mammographic density. Furthermore, in women with low HDL-C, each one SD increase of salivary mid-menstrual 17b-estradiol was associated with an OR of 4.12 (95% confidence intervals; CI, 1.30-13.0) of having abovemedian percent (28.5%), and an OR of 2.5 (95% CI, 1.13-5.50) of having above-median absolute mammographic density (32.4 cm 2 ). On the basis of plausible biologic mechanisms linking HDL-C to breast cancer development, our findings suggest a role of HDL-C, alone or in combination with estrogen, in breast cancer development. However, our small hypothesis generating study requires confirmation in larger studies.Cancer Prev Res; 8(6); 535-44. Ó2015 AACR.

The metabolic syndrome and mammographic breast density in a racially diverse and predominantly immigrant sample of women

“…HDL-C and percent density were also inversely associated in a small sample of postmenopausal women [26]. In contrast, other studies have reported positive associations between HDL-C levels and mammographic density in premenopausal women [25, 43, 44], as well as null associations in premenopausal [22] and postmenopausal women [24, 27]. Most, but not all [45, 46, 38], studies of HDL-C and breast cancer risk support a protective effect for high HDL-C although results across BMI categories and menopausal status have been inconsistent [47–51, 3].…”

Increased Lipids Levels and Breast Cancer

“…14 Low HDL may be associated with higher estrogen levels and absolute mammographic intensity. [15][16][17] In addition, different lipoproteins show that the effect of HDL-cholesterol on breast cancer prognosis is different from the lower breast cancer phenotype, 18 according to progesterone receptor expression. 19 The relation between serum lipids levels and breast cancer risk is unclear; because cholesterol is the precursor to sex steroid hormones, higher levels of cholesterol could possibly increase risk of breast cancer.…”

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

“…Interestingly, low levels of HDL have been associated with increased levels of low-grade inflammation and proinflammatory cytokines [ 9 – 13 ], which in turn induce higher local estradiol levels and breast cell proliferation [ 14 , 15 ]. We have recently observed that HDL-C levels, either alone or in combination with high levels of estrogen or progesterone, were associated with mammographic density phenotypes [ 16 ]. Moreover, lipid molecules have been shown to influence inflammation [ 9 , 10 ], one of the hallmarks in cancer and breast cancer development [ 17 ] and prognosis [ 18 ], and elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients.…”