Evaluation of Breast Lipid Composition in Patients with Benign Tissue and Cancer by Using Multiple Gradient-Echo MR Imaging.

Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three-dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 ± 0.06 vs 0.46 ± 0.10; P < .05) and SFA was higher (0.31 ± 0.07 vs 0.19 ± 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 ± 0.06 vs 0.27 ± 0.05; P < .01) and lower SFA (0.19 ± 0.11 vs 0.30 ± 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. (©) RSNA, 2016 Online supplemental material is available for this article.

Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.

Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17ß-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer.

Modulation of expression of p16 and her2 in rat breast tissues of mammary hyperplasia model by external use of rupifang extract.

OBJECTIVE: To observe the effect of Rupifang Extract in external use on expression of proto-oncogenes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS: Thirty virginal female Wistar rats were randomized into 5 groups, 6 in each, A: blank control group; B: model group; C: the low dose group of Rupifang; D: the middle dose group of Rupifang; and E: The high dose group of Rupifang. The mammary hyperplasia rat models were produced by injecting estradiol benzoate and progesterone and irritating by tail nipping. Drug intervention was also launched during the model formation. After 30 days, the expression of her2 and p16 in breast tissues of rats in each group were detected by the SP immunohistochemical method. RESULTS: Compared with Blank control group, the expression of her2 in breast tissues in Model group was higher, and the expression of p16 was lower (P < 0.05 or P < 0.01). After intervention with Rupifang Extract, compared with Model group, the expression of her2 in breast tissues in Rupifang groups was lower, and the expression of p16 higher (P < 0.05 or P < 0.01). CONCLUSION: The mechanisms of Rupifang Extract in external application for preventing and treating mammary hyperplasia may be reducing the expression of proto-oncogenes her2 and increasing the expression of tumor suppression genes p16.

Tocotrienol levels in adipose tissue of benign and malignant breast lumps in patients in Malaysia.

Data on dietary exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol (alpha-T) in observational studies have failed to provide consistent support for the idea that alpha-T provides women with any protection from breast cancer. In contrast, studies indicate that alpha, gamma, and delta-tocotrienols but not alpha-T have potent anti-proliferative effects in human breast cancer cells. Our aim was to investigate whether there was a difference in tocopherol and tocotrienol concentrations in malignant and benign adipose tissue, in a Malaysian population consuming predominantly a palm oil diet. The study was undertaken using fatty acid levels in breast adipose tissue as a biomarker of qualitative dietary intake of fatty acids. The major fatty acids in breast adipose tissue of patients (benign and malignant) were oleic acid (45-46%), palmitic (28-29%) and linoleic (11-12%). No differences were evident in the fatty acid composition of the two groups. There was a significant difference (p=0.006) in the total tocotrienol levels between malignant (13.7 +/- 6.0 microg/g) and benign (20+/-6.0 microg/g) adipose tissue samples. However, no significant differences were seen in the total tocopherol levels (p=0.42) in the two groups. The study reveals that dietary intake influences adipose tissue fatty acid levels and that adipose tissue is a dynamic reservoir of fat soluble nutrients. The higher adipose tissue concentrations of tocotrienols in benign patients provide support for the idea that tocotrienols may provide protection against breast cancer.

Analysis of zinc transporter, hZnT4 ( Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk.

Zinc deficiency, causing impaired growth and development, may have a nutritional or genetic basis. We investigated two cases of inherited zinc deficiency found in breast-fed neonates, caused by low levels of zinc in the maternal milk. This condition is different from acrodermatitis enteropathica but has similarities to the "lethal milk" mouse, where low levels of zinc in the milk of lactating dams leads to zinc deficiency in pups. The mouse disorder has been attributed to a defect in the ZnT4 gene. Little is known about the expression of the human orthologue, hZnT4 (Slc30A4). Sequence analysis of cDNA, real-time PCR and Western blot analysis of hZnT4, carried out on control cells and cells from unrelated mothers of two infants with zinc deficiency, showed no differences. The hZnT4 gene was highly expressed in mouthwash buccal cells compared with lymphoblasts and fibroblasts. The hZnT4 protein did not co-localise with intracellular free zinc pools, suggesting that hZnT4 is not involved in transport of zinc into vesicles destined for secretion into milk. This observation, combined with phenotypic differences between the "lethal milk" mouse and the human disorder, suggests that the "lethal milk" mouse is not the corresponding model for the human zinc deficiency condition.

In vivo phosphorus-31 magnetic resonance spectroscopy of normal and pathological breast tissues.

In vivo phosphorus-31 magnetic resonance spectroscopy, at 1.5 T, in addition to magnetic resonance imaging and mammography, was performed on the breast tissue of 59 subjects, using a 40 mm or 80 mm surface coil for spectral localization. The patients were divided into three groups: Group 1, 46 control subjects; Group 2, nine patients with breast carcinoma; Group 3, four patients with benign breast disease. The relationship of age, menopausal status, breast size and pattern, use of contraceptive pill and history of breast disease to spectral characteristics of breast tissue was examined for the control group. In multivariate analysis, only menopausal status and age were found to be significantly related to tissue biochemistry. Pre-menopausal women had reduced phosphocreatine (PCr) (%) (p = 0.02), and increased phosphomonoesters (PMEs) and beta-nucleotide triphosphate (beta-NTP) (%) (p = 0.05), while the fat-to-water ratio was higher in older women (p = 0.02). No significant differences were identified between the control subjects and the patients with benign breast disease. When spectra from patients with breast carcinoma were compared with an age-matched volunteer group, alpha- and gamma-NTP (%) were found to be higher in the cancer tissue (p less than 0.01 and p = 0.01, respectively), while PCr (%) was reduced (p less than 0.01). The ratio beta-NTP:PCr was higher in the carcinoma group of patients (p less than 0.05). In vivo phosphorus-31 magnetic resonance spectroscopy is a non-invasive examination which may prove useful in the early differentiation of malignant breast disease from normal and benign conditions.

A comparison of the fatty acid profiles of subcutaneous fat from women with breast cancer, benign breast disease and normal controls.

Using gas chromatography, the fatty acid profile has been measured in subcutaneous fat obtained from women undergoing biopsy for benign and malignant breast conditions. There was a similar proportion of saturated and unsaturated fatty acids in both types or fat, suggesting that long-term differences in fatty acid constituents of diet are unrelated to risk of breast cancer.

Prediction of response to endocrine therapy in pronounced cyclical mastalgia using dynamic tests of prolactin release.

Many of the endocrine agents currently used to treat symptomatic benign breast disease modify the action or secretion of prolactin. We have compared the responses to hormonal therapy with dynamic assessment of prolactin control in 29 patients with cyclical mastalgia and in 7 patients with non-cyclical mastalgia. The tests of prolactin release used were direct stimulation by TRH or dopaminergic blockade by domperidone. These were carried out before treatment in the mastalgic patients and also in 22 age-matched asymptomatic controls. The response to treatment was assessed using a special pain chart and visual linear analogue scale. Patients with cyclical mastalgia could be divided into two groups: those in whom the peak prolactin release was exaggerated (greater than 4000 mU/l) and those in whom the prolactin release was less marked and similar to control subjects and patients with non-cyclical mastalgia. Patients in the cyclical mastalgia group with a high peak prolactin release responded to hormonal treatment significantly more frequently (90%) than those with a normal prolactin release (50%). Basal prolactin levels did not correlate with the response to treatment. In the non-cyclical mastalgia group, no patient had peak prolactin release greater than 4000 mU/l and none responded to therapy. This study indicates that dynamic tests of prolactin release in cyclical mastalgia may be useful in predicting the subsequent satisfactory response to endocrine therapy if a high peak prolactin release is induced.

Radioimmunoassay of human epidermal growth factor in human breast cyst fluid.

Epidermal growth factor (EGF) was assayed radioimmunologically in three secretions of the human mammary gland: milk (n = 16), colostrum (n = 8) and breast cyst fluid (n = 139). The immunoreactivity (immunoreactive EGF) detected in these three fluids corresponds directly to monomeric EGF, as can be shown by the complete cross-reaction with the standard and the identical behaviour in chromatography on Sephadex G50. The mean concentration of EGF is significantly greater in breast cyst fluid (241 +/- 143 ng/ml) and in colostrum (197 +/- 56 ng/ml) than in milk (107 +/- 22 ng/ml). The range of individual values in cyst fluid is large, 5-945 ng/ml. A possible role of EGF as a paracrine or autocrine factor in the pathology of cystic dysplasia of the mammary gland and in the increased risk of malignant transformation is hypothesised.

Ascorbic acid supplementation and five year survival rates in women with early breast cancer.

The effect of long term ascorbic acid (AA) supplementation (3g per day) on 27 women with early breast cancer has been investigated. For comparison a similar but limited study was carried out in patients with benign breast disease. The responses of leucocyte levels of AA to supplementation provided some evidence to suggest that the metabolism and utilisation of the vitamin may be different in these patients. In addition longitudinal measurements of urinary hydroxyproline/creatinine (OHPro/Cr) ratio were carried out in these patients. The long term ingestion of AA did not appear to affect the prognosis of the disease in the early breast cancer group. Similar 5 year survival rates were seen in the unsupplemented and supplemented cancer groups.