Tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to active plasmin, is produced in the rat and mouse hippocampus and participates in neuronal plasticity. To help define the role of tPA in the nervous system, we have analyzed the regulation of its expression in the neuronal cell line PC12. In control cultures, tPA activity is exclusively cell-associated, and no activity is measurable in the culture medium. When the cells are treated with depolarizing agents, such as KCI, tPA activity becomes detectable in the medium. The increased secreted tPA activity is not accompanied by an increase in tPA mRNA levels, and it is not blocked by protein synthesis inhibitors. In contrast, tPA release is abolished by Ca2+ channel blockers, suggesting that chemically induced membrane depolarization stimulates the secretion of preformed enzyme. Moreover, KCI has a similar effect in vivo when administered to the murine brain via an osmotic pump: tPA activity increases along the CA2-CA3 regions and dentate gyrus of the hippocampal formation. These results demonstrate a neuronal activity-dependent secretory mechanism that can rapidly increase the amount of tPA in neuronal tissue.
Evidence shows that Black women diagnosed with breast cancer are substantially less likely to undergo BRCA testing and other multipanel genetic testing compared to White women, despite having a higher incidence of early‐age onset breast cancer and triple‐negative breast cancer (TNBC). Our study identifies predictors of BRCA testing among Black women treated for breast cancer and examines differences between BRCA testers and nontesters. We conducted an analysis of 945 Black women ages 18–64 diagnosed with localized or regional‐stage invasive breast cancer in Pennsylvania and Florida between 2007 and 2009. Logistic regression was used to identify predictors of BRCA 1/2 testing. Few (27%) (n = 252) of the participants reported having BRCA testing. In the multivariate analysis, we found that perceived benefits of BRCA testing (predisposing factor) ([OR], 1.16; 95% CI: 1.11–1.21; P < 0.001), income (enabling factor) ([OR], 2.10; 95% CI: 1.16–3.80; p = 0.014), and BRCA mutation risk category (need factor) ([OR], 3.78; 95% CI: 2.31–6.19; P < 0.001) predicted BRCA testing. These results suggest that interventions to reduce disparities in BRCA testing should focus on identifying patients with high risk of mutation, increasing patient understanding of the benefits of BRCA testing, and removing financial and other administrative barriers to genetic testing.
Genetic testing for hereditary breast and ovarian cancer (HBOC) is recommended for breast cancer patients diagnosed at age ≤ 50 years. Our objective was to examine racial/ethnic differences in genetic testing frequency and results among diverse breast cancer patients. A retrospective cohort study among women diagnosed with breast cancer at age ≤ 50 years from January 2007 to December 2017 at Columbia University in New York, NY. Among 1503 diverse young breast cancer patients, nearly half (46.2%) completed HBOC genetic testing. Genetic testing completion was associated with younger age, family history of breast cancer, and earlier stage, but not race/ethnicity or health insurance status. Blacks had the highest frequency of pathogenic/likely pathogenic (P/LP) variants (18.6%), and Hispanics and Asians had the most variants of uncertain significance (VUS), 19.0% and 21.9%, respectively. The percentage of women undergoing genetic testing increased over time from 15.3% in 2007 to a peak of 72.8% in 2015. Over the same time period, there was a significant increase in P/LP and VUS results. Due to uncertainty about the clinical implications of P/LP variants in moderate penetrance genes and VUSs, our findings underscore the need for targeted genetic counseling education, particularly among young minority breast cancer patients. Keywords BRCA1/2 genetic testing. Multigene panel testing. Young breast cancer patients. Racial/ethnic minorities
Scientific and technologic advances in genomics have revolutionized genetic counseling and testing, targeted therapy, and cancer screening and prevention. Among younger women, African American and Hispanic women have a higher rate of cancers that are associated with hereditary cancer risk, such as triple-negative breast cancer, which is linked to poorer outcomes. Therefore, genetic testing is particularly important in diverse populations. Unfortunately, all races and ethnic groups are not well represented in current genetic testing practices, leading to disparities in cancer prevention and early detection.
The strategy of letrozole as first-line hormonal therapy not only provides an opportunity for extending and improving patient's quality of life, but also is highly cost-effective compared with other generally accepted medical treatments.
Purpose
This integrative review was conducted to examine factors that influence mammography screening and use of cancer genetic services among younger African American women at increased risk for developing breast cancer.
Data sources
Research articles were identified using PubMed, CINAHL, PsychINFO, and Cochrane library to find studies published from 2003 to 2013.
Conclusions
Findings from this review indicate that while younger African American women receive mammograms more often than the general population, they are not being referred for genetic testing when appropriate. This is a major concern because African American women tend to experience more aggressive forms of breast cancer at an earlier age than the general population; it is imperative that they undergo genetic testing for optimal management of their breast cancer risk.
Implications for practice
Nurse practitioners have a significant role in breast cancer screening and genetic testing of at‐risk women, particularly in identifying and referring young women for testing. Further communication efforts are needed to improve young women's knowledge of breast cancer risk and the benefits of genetic testing. Reducing barriers to breast healthcare services requires nursing efforts that focus on populations at greatest risk for poor health outcomes.
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