Polygenic factors are estimated to account for an additional 18% of the familial relative risk of breast cancer, with those at the highest level of polygenic risk distribution having a least a ...twofold increased risk of the disease. Polygenic testing promises to revolutionize health services by providing personalized risk assessments to women at high-risk of breast cancer and within population breast screening programs. However, implementation of polygenic testing needs to be considered in light of its current limitations, such as limited risk prediction for women of non-European ancestry. This article aims to provide a comprehensive review of the evidence for polygenic breast cancer risk, including the discovery of variants associated with breast cancer at the genome-wide level of significance and the use of polygenic risk scores to estimate breast cancer risk. We also review the different applications of this technology including testing of women from high-risk breast cancer families with uninformative genetic testing results, as a moderator of monogenic risk, and for population screening programs. Finally, a potential framework for introducing testing for polygenic risk in familial cancer clinics and the potential challenges with implementing this technology in clinical practice are discussed.
Polygenic risk scores (PRS) are becoming increasingly available in clinical practice to evaluate cancer risk. However, little is known about health professionals' knowledge, attitudes, and ...expectations of PRS. An online questionnaire was distributed by relevant health professional organisations predominately in Australia, Canada and the US to evaluate health professionals' knowledge, views and expectations of PRS. Eligible participants were health professionals who provide cancer risk assessments. Results from the questionnaire were analysed descriptively and content analysis was undertaken of free‐text responses. In total, 105 health professionals completed the questionnaire (genetic counsellors 84%; oncologists 6%; clinical geneticists 4%; other 7%). Although responses differed between countries, most participants (61%) had discussed PRS with patients, 20% had ordered a test and 14% had returned test results to a patient. Confidence and knowledge around interpreting PRS were low. Although 69% reported that polygenic testing will certainly or likely influence patient care in the future, most felt unprepared for this. If scaled up to the population, 49% expect that general practitioners would have a primary role in the provision of PRS, supported by genetic health professionals. These findings will inform the development of resources to support health professionals offering polygenic testing, currently and in the future.
Genetic counselors have long recognized the challenges of working with adolescents and young adults (AYA) and their families. In 2010, a framework of Youth‐friendly Genetic Counseling was developed ...by an expert reference group with the aim to improve both care for AYAs and the experience of health professionals delivering that care. Subsequently, an education workshop was developed aimed to upskill genetic health professionals in youth‐friendly genetic counseling. The workshop was piloted with genetic counselors in Australia and New Zealand. A purpose designed, pre‐ and post‐workshop survey and post‐workshop focus group was utilized for evaluation. Mean confidence scores increased pre‐ and post‐workshop. Participants also demonstrated increases in knowledge regarding: adolescent development; developmental theory; social factors impacting on health; the needs of young people; practice challenges; youth‐friendly engagement, communication, consent and confidentiality; practice approaches; principles of adolescent healthcare; ethical issues; and available services and resources. Focus group data revealed several themes relating to practice challenges, learning gains, barriers, and enablers to clinical translation and workshop feedback. Results demonstrate utility of the workshop in up‐skilling genetic health professionals in the provision of youth‐friendly genetic counseling. Consideration of adaptation and sustainability, by embedding this theoretical and skills‐based workshop as a module within genetic counseling education, is required to ensure practice competence and the best health outcomes for young people and their families.
Rotational grazing management strategies have been promoted as a way to improve the sustainability of native grass-based pasture systems. From disturbance ecology theory, rotational grazing relative ...to continuous grazing can increase pasture productivity by allowing vegetation to recover after short intense grazing periods. This project sought to assess whether soil organic carbon (SOC) stocks would also increase with adoption of rotational grazing management. Twelve pairs of rotationally and continuously grazed paddocks were sampled across a rainfall gradient in South Australia. Pasture productivity approximated as the normalized difference vegetation index (NDVI) was on average no different between management categories, but when the data from all sites were aggregated as log response ratios (rotational/continuous) a significant positive trend of increasing NDVI under rotational grazing relative to continuous grazing was found (R2 = 0.52). Mean SOC stocks (0-30 cm) were 48.3 Mg C ha-1 with a range of 20-80 Mg C ha-1 across the study area with no differences between grazing management categories. SOC stocks were well correlated with rainfall and temperature (multiple linear regression R2 = 0.61). After removing the influence of climate on SOC stocks, the management variables, rest periods, stocking rate and grazing days, were found to be significantly correlated with SOC, explaining 22% of the variance in SOC, but there were still no clear differences in SOC stocks at paired sites. We suggest three reasons for the lack of SOC response. First, changes in plant productivity and turnover in low-medium rainfall regions due to changes in grazing management are small and slow, so we would only expect at best small incremental changes in SOC stocks. This is compounded by the inherent variability within and between paddocks making detection of a small real change difficult on short timescales. Lastly, the management data suggests that there is a gradation in implementation of rotational grazing and the use of two fixed categories (i.e. rotational v. continuous) may not be the most appropriate method of comparing diverse management styles.
Polygenic risk scores (PRSs) are increasingly being implemented to assess breast cancer risk. This study aimed to assess and determine factors associated with uptake of PRS among women at increased ...risk of breast cancer for whom genetic testing to date had been uninformative. Participants were recruited from the Variants in Practice study from which breast cancer PRS had been calculated. Four hundred women were notified by letter of the availability of their PRS and invited to complete a self‐administered survey comprising several validated scales. Considering non‐participants, uptake of PRS was between 61.8% and 42.1%. Multivariate logistic regression identified that women were more likely to receive their PRS if they reported greater benefits (odds ratio OR = 1.17, P = .011) and fewer barriers to receiving their PRS (OR = 0.80, P = .007), had completed higher level education (OR = 3.32, P = .004), and did not have daughters (0.29, P = .006). Uptake of breast cancer PRS varied according to several testing‐ and patient‐related factors. Knowledge of these factors will facilitate the implementation of polygenic testing in clinical practice and support informed decision making by patients.
Objective
Tamoxifen has been demonstrated to reduce breast cancer risk in high‐risk, premenopausal women. Yet, very few young women with hereditary breast and ovarian cancer syndrome in Australia use ...tamoxifen, despite this being a less‐invasive option compared to risk‐reducing mastectomy. This study aims to examine young women's decision‐making about and experience of taking tamoxifen to reduce their breast cancer risk.
Methods
Young women with a BRCA1/2 mutation participated in semi‐structured qualitative interviews, recruited mainly from a metropolitan clinical genetics service. Data were analysed using an inductive, team‐based approach to thematic analysis.
Results
Forty interviews with women aged 20–40 years with a BRCA1/2 mutation were conducted. Eleven women could not recall discussing tamoxifen with their healthcare provider or were too young to commence cancer risk management. Twenty‐three women chose not to use tamoxifen because it is contraindicated for pregnancy or because it did not offer immediate and great enough risk reduction compared to bilateral risk‐reducing mastectomy. Six women who were definite about not wanting to have children during the following 5‐year period chose to use tamoxifen, and most experienced none or transient side effects.
Conclusions
Decision‐making about tamoxifen was nuanced and informed by considerations characteristic of young adulthood, especially childbearing. Therefore, clinical discussions about tamoxifen with young women with a BRCA1/2 mutation must include consideration of their reproductive plans.
As a result of the ongoing global expansion of genetic counseling, the need to formalize a system of professional regulation for genetic counselors was identified in Australasia. In June 2017, under ...the auspices of the Human Genetics Society of Australasia (HGSA), a working party was convened. The purpose of the working party was to provide strategic leadership for the profession of Australasian genetic counselors with a goal to formalize a national regulatory framework for genetic counselors across both Australian and New Zealand jurisdictions. This was ultimately achieved in Australia through full membership with the National Alliance of Self‐Regulating Health Professions (NASRHP) while the profession of genetic counseling in New Zealand is utilizing this framework to establish their regulation pathway. Regulation has a number of implications for genetic counselors, their employers, and the wider community, with the primary purpose of regulation being protection of the public from harm. This paper details the process of formalizing self‐regulation for genetic counselors in Australasia, by defining professional regulation; outlining the purpose of regulation and the status of regulation for genetic counselors in Australasia and internationally, as well as health professionals more broadly; exploring the challenges of establishing regulation in Australasia; and the next steps for regulation in Australasia. Through detailing this process, the intention is to provide a framework to support genetic counseling colleagues internationally as well as other health professions in Australasia to explore and achieve regulation through their respective jurisdiction.
This study aimed to develop an online educational program for using polygenic risk score (PRS) for breast and ovarian cancer risk assessments and to evaluate the impact on the attitudes, confidence, ...knowledge, and preparedness of genetic health care providers (GHPs).
The educational program comprises an online module that covers the theoretical aspects of PRS and a facilitated virtual workshop with prerecorded role-plays and case discussions. Data were collected in pre- and posteducation surveys. Eligible participants were GHPs working in Australian familial cancer clinics registered to recruit patients for a breast and ovarian cancer PRS clinical trial (n = 12).
A total of 124 GHPs completed the PRS education, of whom 80 (64%) and 67 (41%) completed the pre- and posteducation surveys, respectively. Before education, GHPs reported limited experience, confidence, and preparedness using PRS, but they recognized its potential benefits. After education, GHPs indicated improved attitudes (P ≤ .001), confidence (P ≤ .001), knowledge (P ≤ .001), and preparedness (P ≤ .001) to use PRS. Most GHPs thought that the program entirely met their learning needs (73%) and was completely relevant to their clinical practice (88%). GHPs identified PRS implementation barriers, including limited funding models, diversity issues, and need for clinical guidelines.
Our education program improved GHP attitudes, confidence, knowledge, and preparedness for using PRS/personalized risk and provides a framework for the development of future programs.
Polygenic risk scores (PRS) are personalized assessments of disease risk based on the cumulative effect of common low‐risk genetic variants. PRS have been shown to accurately predict women's breast ...cancer risk and are likely to be incorporated into personalized breast cancer risk management programs. However, there are few studies investigating the individual impact of receiving a breast cancer PRS. Existing studies have not demonstrated significant changes in perceived risk or risk management behaviors after receipt of polygenic risk information. The aim of this qualitative study was to explore how women with a family history of breast cancer construct breast cancer risk perceptions after receipt of a breast cancer PRS. Unaffected women with a family history of breast cancer who had not previously received genetic counseling regarding their breast cancer risk were invited to participate in this study. In‐depth, semi‐structured interviews were conducted with 20 women who attended a familial cancer clinic in the Australian states of Victoria and Tasmania. Data were analyzed using an inductive thematic approach. Women's lived experience played a significant role in the construction and maintenance of their breast cancer risk perception. Women's pre‐existing risk perceptions were informed by their family history and their knowledge that breast cancer is a multifactorial disease. Knowing that breast cancer is a multifactorial disease enabled most women to integrate genetic information with their pre‐existing notions of risk. Women reported that the information they received was consistent with their existing notions of personal risk and screening advice. Therefore, the PRS did not lead to a change in perceived risk or risk management behaviors for most women. The results of this study provide insight into how polygenic risk information is integrated with pre‐existing notions of risk, which will inform its implementation into clinical practice.
Hereditary breast cancer is associated with known genetic changes: either variants that affect function in a few rare genes or an ever‐increasing number of common genomic risk variants, which combine ...to produce a cumulative effect, known as a polygenic risk (PR) score. While the clinical validity and utility of PR scores are still being determined, the communication of PR is a new challenge for genetic health professionals. This study investigated how PR scores are discussed in the familial cancer clinic compared with a previous study assessing the communication of monogenic risk (MR) for breast cancer. Sixty‐five PR consultations between genetic health professionals and women at familial risk of breast cancer were audiotaped, transcribed, and coded using a methodology adapted from the MR study. Analysis of consultations shows that while there were similarities in communicating MR and PR, the complexity and novelty of the polygenic information influenced the style of counseling used by genetic health professionals toward a teaching model of genetic counseling, rather than a patient‐centered approach. In particular, compared to MR consultations, in PR consultations significantly fewer counselees (a) were asked about their reasons for attending genetic counseling; or (b) had their information preferences, decision‐making style, medical knowledge, understanding, or concerns checked. In conclusion, it is anticipated that PR scores will become part of standard clinical practice. Thus, it will be important for all genetic health professionals to be appropriately educated so that they can tailor their communication to meet patient needs.
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