Fwd: Metabolic profile of breast cancer in a population of women in southern Spain.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Metabolic profile of breast cancer in a population of women in southern Spain.
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[1]Open Clin Cancer J. 2008; 2: 1-6
Lopez-Saez JB, Martinez-Rubio JA, Alvarez MM, Carrera CG, Dominguez Villar M, de Lomas Mier AG, Doménech C, Senra-Varela A

Background: There are indications that mortality in breast cancer is related with dietary factors, but no study has been large enough to characterise reliably how, this risk is influenced. To establish a logistic regression equation that would predict breast cancer from factors in the endocrinological and metabolic profile, we studied endocrinological and metabolic risk factors that are modified by the diet, in a population of women with breast cancer in southern Spain.Patients and Methods: We carried out a simple a case-control study comparing 204 women with breast cancer (96 premenopausal and 108 postmenopausal women) and 250 healthy control subjects. The predictive variables were basal glycaemia, insulin, glycosylated haemoglobin (HbA1c), C-peptide, insulin-like growth factor-I (IGF-I), total cholesterol, triglycerides, high density lipoprotein-c (HDL-C), low density lipoprotein-c (LDL-C), selenium and Quetelet index (BMI).Results: The metabolic profile differed between pre- and postmenopausal patients, and metabolic alterations were greater in postmenopausal than in premenopausal women. The differences between healthy subjects and breast cancer patients were clearly significant.Conclusions: Our findings have several potential practical applications in the early detection of breast cancer, especially in premenopausal women; in primary prevention; and in the development of a mathematical model of breast carcinogenesis.



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Fwd: Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton.
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[1]PLoS ONE. 2008; 3(7): e2790
Fu XD, Giretti MS, Baldacci C, Garibaldi S, Flamini M, Sanchez AM, Gadducci A, Genazzani AR, Simoncini T

Progesterone plays a role in breast cancer development and progression but the effects on breast cancer cell movement or invasion have not been fully explored. In this study, we investigate the actions of natural progesterone and of the synthetic progestin medroxyprogesterone acetate (MPA) on actin cytoskeleton remodeling and on breast cancer cell movement and invasion. In particular, we characterize the nongenomic signaling cascades implicated in these actions. T47-D breast cancer cells display enhanced horizontal migration and invasion of three-dimensional matrices in the presence of both progestins. Exposure to the hormones triggers a rapid remodeling of the actin cytoskeleton and the formation of membrane ruffles required for cell movement, which are dependent on the rapid phosphorylation of the actin-regulatory protein moesin. The extra-cellular small GTPase RhoA/Rho-associated kinase (ROCK-2) cascade plays central role in progesterone- and MPA-induced moesin activation, cell migration and invasion. In the presence of progesterone, progesterone receptor A (PRA) interacts with the G protein G alpha(13), while MPA drives PR to interact with tyrosine kinase c-Src and to activate phosphatidylinositol-3 kinase, leading to the activation of RhoA/ROCK-2. In conclusion, our findings manifest that progesterone and MPA promote breast cancer cell movement via rapid actin cytoskeleton remodeling, which are mediated by moesin activation. These events are triggered by RhoA/ROCK-2 cascade through partially differing pathways by the two compounds. These results provide original mechanistic explanations for the effects of progestins on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.



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Fwd: Proliferation is the strongest prognosticator in node-negative breast cancer: significance, error sources, alternatives and comparison with molecular prognostic markers.

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Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Proliferation is the strongest prognosticator in node-negative breast cancer: significance, error sources, alternatives and comparison with molecular prognostic markers.
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[1]Breast Cancer Res Treat. 2008 Jul 30;
Baak JP, Gudlaugsson E, Skaland I, Guo LH, Klos J, Lende TH, Søiland H, Janssen EA, Zur Hausen A

Independent studies have shown that in node negative breast cancer patients less than 71 years, the proliferation marker mitotic activity index (MAI) is the strongest, most well reproducible prognosticator and chemotherapy success predictor. The MAI overshadows the prognostic value of tubule formation, nuclear atypia and thereby grade. An often used crude mitotic impression is much less prognostic than the MAI; strict adherence to the MAI protocol is therefore important. The prognostic value of the MAI is age dependent: although patients with a MAI >/= 10 always have a poor prognosis irrespective of age, a low MAI (70 years. PPH3 counts are prognostically stronger than the MAI, and markers such as Cyclin-B and E2FR are promising, but must be validated. Compared with commercial prognostic gene expression signatures, the MAI is at least as strong prognostically, has far fewer false positive results and as such should be included as an independent feature in any node negative breast cancer pathology report.



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Fwd: Risk factors for late relapse and death in patients with early breast cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Risk factors for late relapse and death in patients with early breast cancer.
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[1]Neoplasma. 2008; 55(5): 416-20
C GK, M B, B Z

Adjuvant treatments reduce the risk for recurrence and death from breast cancer; but even 10-15 years after diagnosis, these risks persist. The aim of our study was to identify prognostic factors for relapse and death in the second decade after primary surgery. Patients with early breast cancer treated from 1983-1987 (n=1035) were included. Patients' characteristics, tumor prognostic factors, treatments, data on recurrence and death were obtained from patients' charts and our cancer registry. Median follow-up was 17 (1-23) years. At 10 years after surgery, 515 (49.8%) patients were alive and of them 432 (41.7%) were relapse-free. Of the 432 patients being alive and relapse-free at 10 years 153 (35.4%) had an event thereafter, of them 38 (25%, 9% of all) had a relapse of breast cancer. For this period only the presence of lymphovascular invasion (LVI) and positive estrogen receptors (ER) were found as independent unfavorable prognostic factors for relapse-free (HR 2.09, p=0.007; HR 1.50, p=0.021, respectively) and overall survival (HR 2.15, p=0.006; HR 1.41, p=0.05, respectively) while tumor size, grade and nodal status had no prognostic significance. Positive ER and LVI are independent prognostic factors for relapse and death in the second decade after surgery in patients with early breast cancer. Key words: breast cancer, estrogen receptors, late relapse, lymphovascular invasion.



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Fwd: Dynamic infrared imaging in identification of breast cancer tissue with combined image processing and frequency analysis.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Dynamic infrared imaging in identification of breast cancer tissue with combined image processing and frequency analysis.
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[1]J Med Eng Technol. 2008 Jul-Aug; 32(4): 325-35
Joro R, Lääperi AL, Soimakallio S, Järvenpää R, Kuukasjärvi T, Toivonen T, Saaristo R, Dastidar P

Five combinations of image-processing algorithms were applied to dynamic infrared (IR) images of six breast cancer patients preoperatively to establish optimal enhancement of cancer tissue before frequency analysis. mid-wave photovoltaic (PV) IR cameras with 320x254 and 640x512 pixels were used. The signal-to-noise ratio and the specificity for breast cancer were evaluated with the image-processing combinations from the image series of each patient. Before image processing and frequency analysis the effect of patient movement was minimized with a stabilization program developed and tested in the study by stabilizing image slices using surface markers set as measurement points on the skin of the imaged breast. A mathematical equation for superiority value was developed for comparison of the key ratios of the image-processing combinations. The ability of each combination to locate the mammography finding of breast cancer in each patient was compared. Our results show that data collected with a 640x512-pixel mid-wave PV camera applying image-processing methods optimizing signal-to-noise ratio, morphological image processing and linear image restoration before frequency analysis possess the greatest superiority value, showing the cancer area most clearly also in the match centre of the mammography estimation.



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Fwd: MicroRNA expression in canine mammary cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: MicroRNA expression in canine mammary cancer.
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[1]Mamm Genome. 2008 Jul 30;
Boggs RM, Wright ZM, Stickney MJ, Porter WW, Murphy KE

MicroRNAs (miRNAs) are 18-22-nt noncoding RNAs that are involved in post-transcriptional regulation of genes. Oncomirs, a subclass of miRNAs, include genes whose expression, or lack thereof, are associated with cancers. Until the last decade, the domestic dog was an underused model for the study of various human diseases that have genetic components. The dog exhibits marked genetic and physiologic similarity to the human, thereby making it an excellent model for study and treatment of various hereditary diseases. Furthermore, because the dog presents with distinct, spontaneously occurring mammary tumors, it may serve as a model for genetic analysis and treatments of humans with malignant breast tumors. Because miRNAs have been found to act as both tumor suppressors and oncogenes in several different cancers, expression patterns of ten miRNAs (miR-15a, miR-16, miR-17-5p, miR-21, miR-29b, miR-125b, miR-145, miR-155, miR-181b, let-7f) known to be associated with human breast cancers were compared to malignant canine mammary tumors (n = 6) and normal canine mammary tissue (n = 10). Resulting data revealed miR-29b and miR-21 to have a statistically significant (p

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