Urine Biomarkers of Risk in the Molecular Etiology of Breast Cancer

Endogenous estrogens can be bio-activated to endogenous carcinogens via formation of estrogen quinones. Estrogen-3,4-quinones react with DNA to form mutagenic depurinating estrogen-DNA adducts. The carcinogenicity of endogenous estrogens is related to unbalanced estrogen metabolism leading to excess estrogen quinones and formation of depurinating DNA adducts. The present studies were initiated to confirm that relatively high levels of depurinating estrogen-DNA adducts are present in women at high risk for breast cancer or diagnosed with the disease. These adducts may be biomarkers for early detection of breast cancer risk. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry to analyze urine samples from 40 healthy control women, 40 high-risk women and 40 women with newly diagnosed breast cancer. Estrogen metabolism was shifted from protective methoxylation and conjugation pathways in healthy control women towards activating pathways leading to formation of depurinating DNA adducts in women at high risk or with breast cancer. These results support the hypothesis that breast cancer is initiated by mutations derived from depurination of estrogen-DNA adducts. Therefore, relative levels of depurinating estrogen-DNA adducts could become biomarkers for early detection of breast cancer risk and aid in determining preventive strategies

Frequency format diagram and probability chart for breast cancer risk communication: a prospective, randomized trial

<p>Abstract</p> <p>Background</p> <p>Breast cancer risk education enables women make informed decisions regarding their options for screening and risk reduction. We aimed to determine whether patient education regarding breast cancer risk using a bar graph, with or without a frequency format diagram, improved the accuracy of risk perception.</p> <p>Methods</p> <p>We conducted a prospective, randomized trial among women at increased risk for breast cancer. The main outcome measurement was patients' estimation of their breast cancer risk before and after education with a bar graph (BG group) or bar graph plus a frequency format diagram (BG+FF group), which was assessed by previsit and postvisit questionnaires.</p> <p>Results</p> <p>Of 150 women in the study, 74 were assigned to the BG group and 76 to the BG+FF group. Overall, 72% of women overestimated their risk of breast cancer. The improvement in accuracy of risk perception from the previsit to the postvisit questionnaire (BG group, 19% to 61%; BG+FF group, 13% to 67%) was not significantly different between the 2 groups (<it>P </it>= .10). Among women who inaccurately perceived very high risk (≥ 50% risk), inaccurate risk perception decreased significantly in the BG+FF group (22% to 3%) compared with the BG group (28% to 19%) (<it>P </it>= .004).</p> <p>Conclusion</p> <p>Breast cancer risk communication using a bar graph plus a frequency format diagram can improve the short-term accuracy of risk perception among women perceiving inaccurately high risk.</p

Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update

To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction.; An Expert Panel conducted targeted systematic literature reviews to identify new studies.; A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update.; In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines

Mammographic density, breast cancer risk and risk prediction

In this review, we examine the evidence for mammographic density as an independent risk factor for breast cancer, describe the risk prediction models that have incorporated density, and discuss the current and future implications of using mammographic density in clinical practice. Mammographic density is a consistent and strong risk factor for breast cancer in several populations and across age at mammogram. Recently, this risk factor has been added to existing breast cancer risk prediction models, increasing the discriminatory accuracy with its inclusion, albeit slightly. With validation, these models may replace the existing Gail model for clinical risk assessment. However, absolute risk estimates resulting from these improved models are still limited in their ability to characterize an individual's probability of developing cancer. Promising new measures of mammographic density, including volumetric density, which can be standardized using full-field digital mammography, will likely result in a stronger risk factor and improve accuracy of risk prediction models

The concept of self and ethics in śaṅkara’s philosophy

The concept of Self and ethics in śaṄkara’s philosophy The paper proposes to examine how the identity of the individual Self with the absolute has its bearing on the ethical principal in Śaṅkara’s philosophy. It further analyses that the apparent difference on the empirical plane is due to the ignorance of the individual Self about its own real nature. This ignorance is annihilated when one embarks on the spiritual path following the axiological principles based on the concept of the individual Self which is not different from the Universal Self and discovers one’s own real nature that individual Self is Brahman itself. Obviously these ethical principles have to be based on the ‘principle of equality of all human beings’, which is entailed from the identity of the individual Self with the absolute. Śaṅkara’s approach in this respect permeates his whole philosophical discourse

The Evolution of Mindfulness-Based Physical Interventions in Breast Cancer Survivors

Survivors of breast cancer are faced with a multitude of medical and psychological impairments during and after treatment and throughout their lifespan. Physical exercise has been shown to improve survival and recurrence in this population. Mind-body interventions combine a light-moderate intensity physical exercise with mindfulness, thus having the potential to improve both physical and psychological sequelae of breast cancer treatments. We conducted a review of mindfulness-based physical exercise interventions which included yoga, tai chi chuan, Pilates, and qigong, in breast cancer survivors. Among the mindfulness-based interventions, yoga was significantly more studied in this population as compared to tai chi chuan, Pilates, and qigong. The participants and the outcomes of the majority of the studies reviewed were heterogeneous, and the population included was generally not selected for symptoms. Yoga was shown to improve fatigue in a few methodologically strong studies, providing reasonable evidence for benefit in this population. Improvements were also seen in sleep, anxiety, depression, distress, quality of life, and postchemotherapy nausea and vomiting in the yoga studies. Tai chi chuan, Pilates, and qigong were not studied sufficiently in breast cancer survivors in order to be implemented in clinical practice