Greatly increased occurrence of breast cancers in areas of mammographically dense tissue

INTRODUCTION: Mammographic density is a strong, independent risk factor for breast cancer. A critical unanswered question is whether cancers tend to arise in mammographically dense tissue (i.e. are densities directly related to risk or are they simply a marker of risk). This question cannot be addressed by studying invasive tumors because they manifest as densities and cannot be confidently differentiated from the densities representing fibrous and glandular tissue. We addressed this question by studying ductal carcinoma in situ (DCIS), as revealed by microcalcifications. METHOD: We studied the cranio-caudal and the mediolateral-oblique mammograms of 28 breasts with a solitary DCIS lesion. Two experienced radiologists independently judged whether the DCIS occurred in a mammographically dense area, and determined the density of different areas of the mammograms. RESULTS: It was not possible to determine whether the DCIS was or was not in a dense area for six of the tumors. Of the remaining 22 lesions, 21 occurred in dense tissue (test for difference from expected taken as the percentage of density of the 'mammographic quadrant' containing DCIS; P < 0.0001). A preponderance of DCIS (17 out of 28) occurred in the mammographic quadrant with the highest percentage density. CONCLUSION: DCIS occurs overwhelmingly in the mammographically dense areas of the breast, and pre-DCIS mammograms showed that this relationship was not brought about by the presence of the DCIS. This strongly suggests that some aspect of stromal tissue comprising the mammographically dense tissue directly influences the carcinogenic process in the local breast glandular tissue

Annual Meeting of the International Society of Cancer Metabolism (ISCaM): Cancer Metabolism

Tumors are metabolic entities wherein cancer cells adapt their metabolism to their oncogenic agenda and microenvironmental influences. Metabolically different cancer cell subpopulations collaborate to optimize nutrient delivery with respect to immediate bioenergetic and biosynthetic needs. They can also metabolically exploit host cells. These metabolic networks are directly linked with cancer progression, treatment, resistance, and relapse. Conversely, metabolic alterations in cancer are exploited for anticancer therapy, imaging, and stratification for personalized treatments. These topics were addressed at the 4th annual meeting of the International Society of Cancer Metabolism (ISCaM) in Bertinoro, Italy, on 19–21 October 201

Express Attentional Re-Engagement but Delayed Entry into Consciousness Following Invalid Spatial Cues in Visual Search

Background: In predictive spatial cueing studies, reaction times (RT) are shorter for targets appearing at cued locations (valid trials) than at other locations (invalid trials). An increase in the amplitude of early P1 and/or N1 event-related potential (ERP) components is also present for items appearing at cued locations, reflecting early attentional sensory gain control mechanisms. However, it is still unknown at which stage in the processing stream these early amplitude effects are translated into latency effects. Methodology/Principal Findings: Here, we measured the latency of two ERP components, the N2pc and the sustained posterior contralateral negativity (SPCN), to evaluate whether visual selection (as indexed by the N2pc) and visual-short term memory processes (as indexed by the SPCN) are delayed in invalid trials compared to valid trials. The P1 was larger contralateral to the cued side, indicating that attention was deployed to the cued location prior to the target onset. Despite these early amplitude effects, the N2pc onset latency was unaffected by cue validity, indicating an express, quasiinstantaneous re-engagement of attention in invalid trials. In contrast, latency effects were observed for the SPCN, and these were correlated to the RT effect. Conclusions/Significance: Results show that latency differences that could explain the RT cueing effects must occur after visual selection processes giving rise to the N2pc, but at or before transfer in visual short-term memory, as reflected by th

Future possibilities in the prevention of breast cancer: Luteinizing hormone-releasing hormone agonists

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities

Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]

INTRODUCTION: Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue. Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed. METHODS: A total of 205 women (age range 49–65 years) with Wolfe P2 or DY mammographic breast patterns were randomly assigned to receive either a red clover-derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein) or placebo. Change in mammographic breast density, serum oestradiol, FSH, LH, menopausal symptoms and lymphocyte tyrosine kinase activity from baseline to 12 months were assessed. RESULTS: A total of 177 women completed the trial. Mammographic breast density decreased in both groups but the difference between the treatment and placebo was not statistically significant. There was a significant interaction between treatment group and oestrogen receptor (ESR1) PvuII polymorphism for the change in estimated percentage breast density (mean ± standard deviation): TT isoflavone 1.4 ± 12.3% and TT placebo -9.6 ± 14.2%; CT isoflavone -5.2 ± 12.0% and CT placebo -2.8 ± 10.3%; and CC isoflavone -3.4 ± 9.7% and CC placebo -1.1 ± 9.5%. There were no statistically significant treatment effects on oestradiol, FSH, or LH (assessed only in postmenopausal women), or on lymphocyte tyrosine kinase activity. Baseline levels of menopausal symptoms were low, and there were no statistically significant treatment effects on frequency of hot flushes or other menopausal symptoms. CONCLUSION: In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density, the isoflavone supplement did not increase mammographic breast density in this population of women. Furthermore, there were no effects on oestradiol, gonadotrophins, lymphocyte tyrosine kinase activity, or menopausal symptoms

Epidemiology and cost of herpes zoster and postherpetic neuralgia among patients treated in primary care centres in the valencian community of Spain

<p>Abstract</p> <p>Background</p> <p>Data on the epidemiology and costs related to herpes zoster (HZ) and postherpetic neuralgia (PHN) in Spain are scarce; therefore, studies are needed to evaluate the epidemiological and economic impact of HZ and its most common complication, PHN. The present study aimed to estimate the clinical and economic burden of HZ and PHN in Valencia (Spain).</p> <p>Methods</p> <p>We prospectively analyzed the burden of HZ and PHN and their attributable costs in patients from 25 general practices in the Autonomous Community of Valencia serving 36,030 persons aged > 14 years. All patients with a clinical diagnosis of HZ who attended these centers between December 1^st2006 and November 30^th2007 were asked to participate. Patients included were followed for 1 year.</p> <p>Results</p> <p>Of the 130 cases of HZ followed up, continued pain was experienced by 47.6% (95% confidence interval (CI) = 35.6-56.7%) at 1 month after rash onset, by 14.5% (95% CI = 7.8-1.2%) at 3 months, by 9.0% (95% CI = 3.7-14.3%) at 6 months, and by 5.9% (95% CI = 1.5-10.3%) at 12 months. The percentage of patients with PHN increased with age, from 21.4% (95% CI = 8.3-40) in patients < 50 years to 59.2% (95% CI = 44.4-74) in patients ≥ 70 years. The estimated total cost for the 130 HZ cases during the follow-up period was €49,160 ($67,349). Mean cost per patient was €378 (range 53-2,830) ($517, range 73-3,877).</p> <p>Conclusions</p> <p>This study shows that PHN is a relatively common complication of HZ and that both conditions combined give rise to a significant clinical and economic burden for patients and providers.</p

Dietary intake and breast density in high-risk women: a cross-sectional study

Background Women with a family history of breast cancer may be at higher risk for breast cancer, but few previous studies evaluating diet and breast cancer have focused on such women. The objective of the present study was to determine whether diet, a modifiable risk factor, is related to breast density among women at high genetic risk for breast cancer. Methods Women with at least one first-degree or second-degree relative with breast cancer or ovarian cancer participating in the Fox Chase Cancer Center Family Risk Assessment Program completed health history and food frequency questionnaires and received standard screening mammograms. Cranial–caudal mammographic images were classified into the four Breast Imaging Reporting and Data System categories ranging from \u27entirely fatty\u27 to \u27extremely dense\u27. Logistic regression analysis using proportional odds models for polychotomous outcomes provided estimates of odds ratios for having a higher category versus a lower category of breast density. Results Among 157 high-risk women, breast density was inversely associated with vitamin D intake (odds ratio for third tertile versus first tertile, 0.5; 95% confidence interval, 0.2–1.0). In contrast, intakes above the median level for protein (odds ratio, 3.0; 95% confidence interval, 1.3–6.9) and above the median level for animal protein (odds ratio, 4.3; 95% confidence interval, 1.8–10.3) were associated with higher breast density, but only among women whose family history did not reflect a known familial cancer syndrome or a breast cancer predisposition gene. Conclusion For women with a strong family history that was not associated with known cancer syndromes, dietary factors may be associated with breast density, a strong predictor of breast cancer risk. Since women with strong family history are often very motivated to change their lifestyle habits, further studies are needed to confirm whether changes in diet will change the breast density and the subsequent onset of breast cancer in these women

High-risk mammographic parenchymal patterns and anthropometric measures: a case–control study

Mammographic parenchymal patterns are related to breast cancer risk and are also affected by anthropometric measure. We carried out a case–control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of body size and shape and breast size on mammographic patterns. Women in the highest quartile of body mass index (BMI) distribution were significantly less likely to have a high-risk pattern (odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.08–0.52, P-value for trend = 0.001) compared to those in the lowest quartile. Relative to women with a waist to hip ratio (WHR) of less than 0.75, the OR of having a high-risk pattern in women with a WHR greater than 0.80 was 0.30 (95% CI 0.14–0.63). Breast size as measured by cup size was significantly and negatively related to high-risk pattern. Our study indicates that both BMI and WHR are negatively associated with high-risk patterns. However, both phenomena are associated with increased risk of breast cancer in post-menopausal women. This negative confounding of two positive risk factors means that the effect of parenchymal patterns on risk will tend to be underestimated when not adjusted for BMI and WHR and vice versa. Thus we may have underestimated the importance of BMI and mammographic parenchymal patterns in the past. Further studies are needed to determine a measure of parenchymal density that is independent of anthropometric measures and breast size. © 1999 Cancer Research Campaig

Human papillomavirus vaccine introduction in low-income and middle-income countries: guidance on the use of cost-effectiveness models

BACKGROUND: The World Health Organization (WHO) recommends that the cost effectiveness of introducing human papillomavirus (HPV) vaccination is considered before such a strategy is implemented. However, developing countries often lack the technical capacity to perform and interpret results of economic appraisals of vaccines. To provide information about the feasibility of using such models in a developing country setting, we evaluated models of HPV vaccination in terms of their capacity, requirements, limitations and comparability. METHODS: A literature review identified six HPV vaccination models suitable for low-income and middle-income country use and representative of the literature in terms of provenance and model structure. Each model was adapted by its developers using standardised data sets representative of two hypothetical developing countries (a low-income country with no screening and a middle-income country with limited screening). Model predictions before and after vaccination of adolescent girls were compared in terms of HPV prevalence and cervical cancer incidence, as was the incremental cost-effectiveness ratio of vaccination under different scenarios. RESULTS: None of the models perfectly reproduced the standardised data set provided to the model developers. However, they agreed that large decreases in type 16/18 HPV prevalence and cervical cancer incidence are likely to occur following vaccination. Apart from the Thai model (in which vaccine and non-vaccine HPV types were combined), vaccine-type HPV prevalence dropped by 75% to 100%, and vaccine-type cervical cancer incidence dropped by 80% to 100% across the models (averaging over age groups). The most influential factors affecting cost effectiveness were the discount rate, duration of vaccine protection, vaccine price and HPV prevalence. Demographic change, access to treatment and data resolution were found to be key issues to consider for models in developing countries. CONCLUSIONS: The results indicated the usefulness of considering results from several models and sets of modelling assumptions in decision making. Modelling groups were prepared to share their models and expertise to work with stakeholders in developing countries. Please see related article: http://www.biomedcentral.com/1741-7007/9/55