: Interest in hereditary breast cancer has increased rapidly among all health care providers as well as the laity. A major problem for health care providers, however, is the time and skill required ...for gathering family history, interpreting the pedigree, and providing genetic counseling for the high‐risk patient so that BRCA testing, when indicated, can be pursued and screening and prevention strategies employed by the patient. The fields of hereditary cancer and molecular biology have developed at a rate that makes it difficult for physicians to keep up with this explosive knowledge. Therefore, “Who is going to take care of all of these crucial matters for patient benefit?” is a germane question. Our experience has confirmed that the advanced practice oncology nurse who is interested in cancer genetics can become skilled at providing this service to the patient and his/her family. This study portrays the role of such an oncology nurse in meeting this important public health challenge, with special attention devoted to the logistics of this role in the rapidly emerging field of hereditary breast cancer.
: Hereditary breast cancer (BC) is heterogeneous to the extent that no two high‐risk patients can be considered as being the same. These individual differences are magnified further when patients’ ...emotional response to all facets of hereditary BC are considered, particularly issues surrounding gene testing. A series of case histories have been provided that illustrate the wide range of attitudes, feelings, and emotional responses explained by patients when learning of their hereditary cancer risk status. The role of the oncology nurse‐genetic counselor has been described in each of these family reports.
: Some members of hereditary breast‐ovarian cancer (HBOC) families may not participate in BRCA testing to determine their mutation status in part because they are unaware of their cancer risk and ...the availability of BRCA testing. Participation in a family information service (FIS), of which we have provided more than 100 sessions during the past 30 years, has been seen to effectively allow family members to be educated regarding their cancer genetic risk and potential benefits from cancer control measures such as mutation testing. However, the effect of the FIS on the rate of mutation testing has not been studied. One thousand five hundred seventy‐four eligible (>18‐year old, at a 25% or higher pedigree risk) members from 60 extended HBOC families with BRCA1/2 mutations were invited to attend a FIS to learn about their risk and undergo genetic testing. The rates of mutation testing were compared between those who had attended an FIS, and those who had not with chi‐squared test and logistic regression analysis. Seventy five percent (334/444) of FIS attendees had undergone mutation testing following or during an FIS which was significantly higher than the 33.8% (382/1130) rate among nonattendees (p < 0.0001). Logistic regression analysis showed that FIS attendance, breast‐ovarian cancer history, gender, and age were significant variables for undertaking a mutation test. FIS attendance significantly increased the rate of mutation testing among high‐risk family members.
Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal ...cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence.
In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.
5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p<0·0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A>T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7–56% of carriers having a colorectal cancer penetrance of less than 20%, 9–44% having a penetrance of more than 80%, and only 10–19% having a penetrance of 40–60%.
Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome.
National Health and Medical Research Council, Australia.
Perinatal mental health conditions are the most common complication of pregnancy and childbirth in the United States and the leading cause of maternal deaths. While one in five women will experience ...a perinatal mental health condition, less than 25% will receive treatment. The goal of this project was to develop a sustainable perinatal mental health educational program to be integrated into routine prenatal care services at a not-for-profit community birthing hospital.The project evaluated the effectiveness of a novel educational program focused on mental health literacy and maternal wellbeing during the perinatal period. Participants were recruited using convenience sampling and attended a two-hour group session offered both in-person and virtually. The participants (n=10) were asked to complete a pre-intervention questionnaire which included a demographic survey, knowledge pretest, and the WHO-5 Wellbeing Index. Following the session, the participants completed a post-intervention questionnaire. The primary aim was to improve mental health literacy and self-awareness during the perinatal period with the implementation of an educational health promotion program. Analysis of pre- and post-intervention scores (n=10) were compared using the Wilcoxon signed rank test found statistical increases in knowledge on all knowledge-based questions. One of two secondary aims was to improve perceived wellbeing in the postpartum period compared to pregnancy by implementing a postpartum wellness plan. Participant’s perception of self-care and wellbeing were evaluated before the intervention. Using the Kruskal-Wallis test, participant’s WHO-5 Wellbeing scores were compared to their participation in self-care activities. No statistical significance was found (H = 2.94, p =.229). Postpartum data was not collected because none of the participants experienced childbirth during the data collection period. The final secondary aim was to reduce stigma and ensure participants were aware of resources. Due to the small sample, reducing stigma was not found statistically significant following the intervention (Wilcoxon signed ranks test Z =1.41, p = .157).This project supports integrating mental health and wellness education into prenatal care to improve knowledge and mental health literacy in pregnant persons. The project provides a foundation for future research and development of perinatal mental health interventions.
Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancers. We sought to estimate the prevalence of cancer-related distress and to identify predictors of ...distress in an international sample of unaffected women with a BRCA mutation.
Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the United States, Canada, the United Kingdom, Australia and from a national advocacy group. Using an online survey, we asked about cancer risk reduction options and screening, and we measured cancer-related distress using the Impact of Event Scale.
Among 576 respondents, mean age was 40.8 years (SD = 8.1). On average 4.9 years after a positive test result, 16.3% of women reported moderate-to-severe cancer-related distress. Women who had undergone risk-reducing breast and ovarian surgery were less likely to have (moderate or severe) cancer-related distress compared to other women (22.0% versus 11.4%, P value = 0.007). Women recruited from the advocacy group were more likely to have cancer-related distress than other women (21.6% versus 5.3%, P value = 0.002).
Approximately 16% of women with a BRCA1 or BRCA2 mutation experience distress levels comparable to those of women after a cancer diagnosis. Distress was lower for women who had risk-reducing surgery.
Synthetic cannabinoids (SC's) began to gain popularity around the world in 2009. Since then, many of the compounds have been outlawed and methods developed to detect them and their metabolites using ...mass spectrometry. Our work investigated the possibility of developing a colorimetric presumptive test. The SC JWH-019 was synthesized and its ketone targeted as a possible reaction site. Many SC's contain ketones and thus a reaction at this site would be applicable to many of the compounds. Since JWH-019 is costly and time consuming to synthesize, much of the experimental work was done using benzophenone (BP). BP contains a diaryl ketone making it comparable to JWH-019. Our initial work studied existing presumptive tests, one for SC's and one for cannabis. Both gave negative results for JWH-019. From there, we looked at synthesizing imines that might be colored. We studied reactions using dinitrophenylhydrazone, hydrazine, aniline and neutral red. Through these reactions it became apparent that the ketones on BP and JWH-019 were reluctant to react. Finally, we studied forming imines of BP with either ethylenediamine (en) or semicarbazide. The resulting product was then used to produce a metal complex. A complex formed between the en-BP product and Cu2+ provided a change in color, but the en-BP imine proved difficult to obtain and the results were not consistent.
To evaluate the predictors of mortality, including ER status, in women with a BRCA2 mutation and breast cancer.
Eligible participants were identified from within two longitudinal cohorts. These ...patients were selected because they were diagnosed with breast cancer between 1975 and 2015 and carried a BRCA2 mutation. Data were abstracted from the medical record and pathology report. We analysed the effects of ER status and other variables on breast cancer specific survival using a Cox proportional hazards model.
Three hundred ninety women with breast cancer and a BRCA2 mutation were included in the analysis. The mean follow-up time was 12.3 years (range 1-39 years) and 89 subjects died (22.8%). In the multivariate analysis, women with ER-positive tumours were more likely to die than women with ER-negative tumours (HR 2.08, 95% CI 0.99-4.36, p = 0.05), and this was of borderline significance. For the 233 women with ER-positive tumours the 20-year survival rate was 62.2%, compared to 83.7% for 58 women with ER-negative tumours (p = 0.03).
The majority of women with a BRCA2 mutation present with ER-positive breast cancer, and for these women, prognosis may be worse than for BRCA2 carriers with ER-negative breast cancer.
PDF
