Association of adult attachment with delays in accessing specialist care in women with ovarian cancer.

OBJECTIVE: Advanced stage at diagnosis and delayed presentation are common in ovarian cancer (OC). The objective of the current study was to explore the association of adult attachment pattern with delays in accessing specialist oncology care in patients with OC. METHODS: A cross-sectional structured interview study of patients with OC presenting to an Indian cancer center was undertaken. Consenting patients completed Experiences of Close Relationships-Relationship Style questionnaire (ECR-RS) and Medical Outcome Survey-Social Support Survey (MOS-SSS). Multivariate linear regression with "time to presentation to cancer specialist" as the dependent variable was undertaken. RESULTS: In all, 132 of 155 (85%) patients with OC who were invited were interviewed. An increased ECR-RS attachment anxiety score (P = .01) and being part of a multigenerational extended household (P = .04) were both independently associated with delay in presentation to a cancer specialist. There was no association between delay in presentation and social support. CONCLUSIONS: Among patients with OC, adult attachment may contribute to delays in presentation. It may be important for the cancer symptom awareness efforts in primary care to include educating physicians on recognizing and interacting with patients with insecure attachment styles. The association of delays in presentation for women with OC living in multigenerational extended households needs more indepth exploration.Supplemental data for this article is available online at https://doi.org/10.1080/07347332.2022.2025510 .

Health care professionals' attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.

BACKGROUND: Ovarian cancer is usually diagnosed at a late stage when outcomes are poor. Personalised ovarian cancer risk prediction, based on genetic and epidemiological information and risk stratified management in adult women could improve outcomes. Examining health care professionals' (HCP) attitudes to ovarian cancer risk stratified management, willingness to support women, self-efficacy (belief in one's own ability to successfully complete a task), and knowledge about ovarian cancer will help identify training needs in anticipation of personalised ovarian cancer risk prediction being introduced. METHODS: An anonymous survey was distributed online to HCPs via relevant professional organisations in the UK. Kruskal-Wallis tests and pairwise comparisons were used to compare knowledge and self-efficacy scores between different types of HCPs, and attitudes toward population-based genetic testing and risk stratified management were described. Content analysis was undertaken of free text responses concerning HCPs willingness to discuss risk management options with women. RESULTS: One hundred forty-six eligible HCPs completed the survey: oncologists (31%); genetics clinicians (30%); general practitioners (22%); gynaecologists (10%); nurses (4%); and 'others'. Scores for knowledge of ovarian cancer and genetics, and self-efficacy in conducting a cancer risk consultation were generally high but significantly lower for general practitioners compared to genetics clinicians, oncologists, and gynaecologists. Support for population-based genetic testing was not high (<50%). Attitudes towards ovarian cancer risk stratification were mixed, although the majority of participants indicated a willingness to discuss management options with patients. CONCLUSIONS: Larger samples are required to investigate attitudes to population-based genetic testing for ovarian cancer risk and to establish why some HCPs are hesitant to offer testing to all adult female patients. If ovarian cancer risk assessment using genetic testing and non-genetic information including epidemiological information is rolled out on a population basis, training will be needed for HCPs in primary care to enable them to provide appropriate support to women at each stage of the process.

Awareness, knowledge, perceptions, and attitudes towards genetic testing for cancer risk among ethnic minority groups: a systematic review.

BACKGROUND: Genetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups' awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups. METHODS: A search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included. RESULTS: Forty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment. CONCLUSION: Interventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and across a broader spectrum of ethnic minority groups to develop effective culturally sensitive approaches for cancer prevention.

Impact of a decision aid about stratified ovarian cancer risk-management on women's knowledge and intentions: a randomised online experimental survey study.

BACKGROUND: Risk stratification using genetic and other types of personal information could improve current best available approaches to ovarian cancer risk reduction, improving identification of women at increased risk of ovarian cancer and reducing unnecessary interventions for women at lower risk. Amounts of information given to women may influence key informed decision-related outcomes, e.g. knowledge. The primary aim of this study was to compare informed decision-related outcomes between women given one of two versions (gist vs. extended) of a decision aid about stratified ovarian cancer risk-management. METHODS: This was an experimental survey study comparing the effects of brief (gist) information with lengthier, more detailed (extended) information on cognitions relevant to informed decision-making about participating in risk-stratified ovarian cancer screening. Women with no personal history of ovarian cancer were recruited through an online survey company and randomised to view the gist (n = 512) or extended (n = 519) version of a website-based decision aid and completed an online survey. Primary outcomes were knowledge and intentions. Secondary outcomes included attitudes (values) and decisional conflict. RESULTS: There were no significant differences between the gist and extended conditions in knowledge about ovarian cancer (time*group interaction: F = 0.20, p = 0.66) or intention to participate in ovarian cancer screening based on genetic risk assessment (t(1029) = 0.43, p = 0.67). There were also no between-groups differences in secondary outcomes. In the sample overall (n = 1031), knowledge about ovarian cancer increased from before to after exposure to the decision aid (from 5.71 to 6.77 out of a possible 10: t = 19.04, p < 0.001), and 74% of participants said that they would participate in ovarian cancer screening based on genetic risk assessment. CONCLUSIONS: No differences in knowledge or intentions were found between women who viewed the gist version and women who viewed the extended version of a decision aid about risk-stratified ovarian cancer screening. Knowledge increased for women in both decision aid groups. Further research is needed to determine the ideal volume and type of content for decision aids about stratified ovarian cancer risk-management. TRIAL REGISTRATIONS: This study was registered with the ISRCTN registry; registration number: ISRCTN48627877 .

Genetic testing and personalized ovarian cancer screening: a survey of public attitudes.

BACKGROUND: Advances in genetic technologies are expected to make population-wide genetic testing feasible. This could provide a basis for risk stratified cancer screening; but acceptability in the target populations has not been explored. METHODS: We assessed attitudes to risk-stratified ovarian cancer (OC) screening based on prior genetic risk assessment using a survey design. Home-based interviews were carried out by the UK Office of National Statistics in a population-based sample of 1095 women aged 18-74. Demographic and personal correlates of attitudes to risk-stratified OC screening based on prior genetic risk assessment were determined using univariate analyses and adjusted logistic regression models. RESULTS: Full data on the key analytic questions were available for 829 respondents (mean age 46 years; 27 % 'university educated'; 93 % 'White'). Relatively few respondents felt they were at 'higher' or 'much higher' risk of OC than other women of their age group (7.4 %, n = 61). Most women (85 %) said they would 'probably' or 'definitely' take up OC genetic testing; which increased to 88 % if the test also informed about breast cancer risk. Almost all women (92 %) thought they would 'probably' or 'definitely' participate in risk-stratified OC screening. In multivariate logistic regression models, university level education was associated with lower anticipated uptake of genetic testing (p = 0.009), but with more positive attitudes toward risk-stratified screening (p <0.001). Perceived risk was not significantly associated with any of the outcome variables. CONCLUSIONS: These findings give confidence in taking forward research on integration of novel genomic technologies into mainstream healthcare.

The sex hormone system in carriers of BRCA1/2 mutations: a case-control study.

BACKGROUND: Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutations is disproportionately high. Sex hormone dysregulation and altered end-organ hormone sensitivity might explain this organ-specific penetrance. We sought to identify differences in hormone regulation between carriers of BRCA1/2 and women who are negative for BRCA1/2 mutations. METHODS: We assessed endometrial thickness for each menstrual cycle day (as an index of hormone regulation) in 393 scans from 228 women in the UK Familial Ovarian Cancer Screening Study (UK FOCSS) known to carry either mutation and 1573 scans from 754 women known to be negative for the mutations. To quantify differences in endometrial thickness we focused on days 10-14 and days 21-26, and calculated the area under the curve. We then compared serum oestradiol and progesterone titres during these days of the menstrual cycle in the same groups. Follicular and luteal oestradiol and progesterone serum titres were grouped into quartiles and odds ratios were calculated with logistic regression. FINDINGS: Follicular phase endometrial thickness of carriers of the mutations adjusted for age and day of the menstrual cycle was higher (odds ratio [OR] 1·11, 95% CI 1·03-1·20; p=0·0063) and luteal phase endometrial thickness lower (0·90, 0·83-0·98; p=0·027) than for women negative for the mutations. Median luteal phase titres of progesterone were 121% higher (p=0·00037) in carriers than in women negative for the mutations, and for oestradiol were 33% higher (p=0·007)-ie, 59% of carriers had concentrations of serum progesterone that would have been in the top quartile of concentrations in the control group (OR 8·0, 95% CI 2·1-52·57; p=0·008). INTERPRETATION: Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and progesterone-known risk-factors for breast cancer. Higher titres of oestradiol in carriers are compatible with this hormone having a role in ovarian carcinogenesis in such women. Our findings could not be explained by differential contraceptive pill use.

A qualitative study of women's experiences of familial ovarian cancer screening.

OBJECTIVE: One risk management strategy that women at increased familial risk of ovarian cancer may use is screening. Until recently, this has been available as part of the UK Familial Ovarian Cancer Screening Study (UKFOCSS), using ultrasound scans of the ovaries and tumour marker blood tests. The present study aimed to gain an in-depth understanding of women's experiences of participating in ovarian cancer screening. METHODS: Semi-structured interviews were conducted with 48 UKFOCSS participants. Interviews were recorded, transcribed and relevant sections analysed using a framework approach. RESULTS: Screening provided women with reassurance which they found beneficial. A sense of privilege, as well as feeling proactive in potentially detecting ovarian cancer at an early stage was described. The wider benefit to research and the potential impact this could have on others was also important to women. Negative experiences of screening included worry about the screening tests and results, false reassurance by test results and disappointment with ineffective screening. Aspects of the screening study, such as the logistics, organisation and communication, were described as both good and problematic. When weighed up by the women, most described an overall positive experience of screening. CONCLUSIONS: Women reported both positive and negative experiences of screening. Overall, screening seemed to be an acceptable risk management strategy to most women who participated in this interview study. Improvements could be made particularly in helping women to understand the limitations of familial ovarian cancer screening in order to avoid false reassurance.

Withdrawal from familial ovarian cancer screening for surgery: findings from a psychological evaluation study (PsyFOCS).

OBJECTIVE: A prospective psychological evaluation study of familial ovarian cancer screening (PsyFOCS) is underway in partnership with the UK Familial Ovarian Cancer Screening Study (UK FOCSS Phase 2). One of the aims of PsyFOCS is to examine factors associated with withdrawal from the UK FOCSS prior to the onset of 4-monthly screening. METHOD: 1999 of 3224 women completed a baseline questionnaire. 110 (5.5%) women withdrew from screening prior to their first routine Phase 2 screen, of which 73 (66.4% of withdrawals) had withdrawn because they had undergone removal of their ovaries and fallopian tubes (withdrawn group). The comparison group consisted of 1868 women who remained on screening. The baseline questionnaire included measures of cancer-specific distress, anxiety, depression and illness perceptions. RESULTS: Logistic regression analysis indicated that having had prior annual (Phase 1) screening (OR=13.34, p<.01), past experience of further tests (OR=2.37, p<.01) and greater cancer-specific distress (OR=1.38, p<.01) were associated with withdrawal for surgery. Belief in ageing as a cause of ovarian cancer was also associated with withdrawal (OR=1.32, p=.05). CONCLUSION: These cross-sectional data suggest that withdrawal from familial ovarian cancer screening may be influenced by both clinical and psychological factors. These may reflect women's experience of the drawbacks of screening and increased concern about ovarian cancer risk, as well as having opportunities to consider surgery as an alternative risk management strategy whilst using screening as an interim measure.

Psychological outcomes of familial ovarian cancer screening: no evidence of long-term harm.

OBJECTIVES: Ovarian cancer screening for women at increased genetic risk in the UK involves 4-monthly CA125 tests and annual ultrasound, with further tests prompted by an abnormal result. The study evaluated the longer-term psychological and behavioural effects of frequent ovarian screening. METHODS: Women completed T1 questionnaires before their first routine 4-monthly CA125 test, and T2 follow-up questionnaires one week after their result. Women with abnormal results completed a further questionnaire one week after return to routine screening (T3 primary end-point). T4 questionnaires were sent at nine months. Measures included cancer distress, general anxiety/depression, reassurance, and withdrawal from screening. RESULTS: A total 1999 (62%) of 3224 women completed T1 questionnaires. T2 questionnaires were completed by 1384/1609 participants (86%): 1217 (89%) with normal results and 167/242 (69%) with abnormal results. T3 questionnaires were completed by 141/163 (87%) women, with 912/1173 (78%) completing T4 questionnaires. Analysis of covariance indicated that, compared to women with normal results, women with abnormal results reported moderate cancer distress (F = 27.47, p ≤ .001, η(2) = 0.02) one week after their abnormal result and were significantly more likely to withdraw from screening (OR = 4.38, p ≤ .001). These effects were not apparent at T3 or T4. The effect of screening result on general anxiety/depression or overall reassurance was not significant. CONCLUSIONS: Women participating in frequent ovarian screening who are recalled for an abnormal result may experience transient cancer-specific distress, which may prompt reconsideration of risk management options. Health professionals and policy makers may be reassured that frequent familial ovarian screening does not cause sustained psychological harm.

Quality Assessment and Production of Human Cells for Clinical Use.

Cell transplantation therapy aspires to repair and restore lost function while minimizing the risk of harm. The potential for harm arises from cell instability, variability, inappropriate behavior, and/or transmission of adventitious pathogens. Quality assured and controlled assessment and production of human cells for clinical use ensures that the risk of harm is minimized. Application of quality standards requires thorough planning and consultation with regulatory authorities on process and product specifications, as early as possible at the research and development (R&D) stage. Here we outline considerations applicable to all human cells in relation to regulatory governance, the route to the clinic and Cell Therapy Product (CTP) characterization, with special emphasis on human pluripotent stem cells (hPSC).

Attitudes towards a programme of risk assessment and stratified management for ovarian cancer: a focus group study of UK South Asians' perspectives.

OBJECTIVE: Population-based risk assessment, using genetic testing and the provision of appropriate risk management, could lead to prevention, early detection and improved clinical management of ovarian cancer (OC). Previous research with mostly white British participants found positive attitudes towards such a programme. The current study aimed to explore the attitudes of South Asian (SA) women and men in the UK with the aim of identifying how best to implement such a programme to minimise distress and maximise uptake. DESIGN: Semistructured qualitative focus group discussions. SETTING: Community centres across North London and Luton. PARTICIPANTS: 49 women and 13 men who identified as SA (Indian, Pakistani or Bangladeshi), which constitutes the largest non-European ethnic minority group in the UK. METHODS: Seven community-based focus groups were held. Group discussions were transcribed verbatim, coded and analysed thematically. RESULTS: Awareness and knowledge of OC symptoms and specific risk factors was low. The programme was acceptable to most participants and attitudes to it were generally positive. Participants' main concerns related to receiving a high-risk result following the genetic test. Younger women may be more cautious of genetic testing, screening or risk-reducing surgery due to the importance of marriage and childbearing in their SA cultures. CONCLUSIONS: A crucial first step to enable implementation of population-based genetic risk assessment and management in OC is to raise awareness of OC within SA communities. It will be important to engage with the SA community early on in programme implementation to address their specific concerns and to ensure culturally tailored decision support.

Study comparing two types of screening provision for people with von Hippel-Lindau disease.

Patients diagnosed with von Hippel-Lindau disease (vHL) require life-long surveillance for this multi-system disease. It is therefore important to assess the comprehensiveness of screening provision, as well as identify what type of screening service is most likely to encourage regular patient attendance. This descriptive study reports on two types of screening service: single appointment One Stop (OS) clinics and multiple appointment Ad Hoc (AH) clinics. One hundred and seventeen vHL patients from eight regional genetics centres were approached to take part. Seventy-two (61.5%) returning a completed study questionnaire: fifty-four (75%) were screened at OS clinics and eighteen (25%) at AH clinics. Comprehensiveness of screening, attendance rates, patient ratings of quality of care and levels of psychological morbidity were compared between the two types of service. While levels of disease severity were similar in patients screened at OS and AH clinics, those seen at OS clinics were screened for twice as many site-specific vHL manifestations compared to those seen at AH clinics (P < 0.0001). More patients at OS clinics regularly attended their screening appointments compared to those at AH clinics (P = 0.0045). There was no difference in the quality of care reported by patients attending the two types of screening service and few problems were reported. Twenty-nine percent of respondents were categorised as clinically anxious and 13% as clinically depressed. These findings suggest that an optimum vHL screening service is one based on OS clinics offering regular comprehensive surveillance and psychological support.

Decline in use of hormone therapy among postmenopausal women in the United Kingdom.

OBJECTIVE: There has been controversy about the results of the Women's Health Initiative and the Million Women Study and uncertainty about their impact on hormone therapy (HT) use. This study documents recent trends in HT use in postmenopausal women in the United Kingdom. DESIGN: Between April 2001 and September 2005, 202,638 postmenopausal women aged 50 to 74 and with no history of bilateral oophorectomy were recruited to the United Kingdom Collaborative Trial of Ovarian Cancer Screening. The proportion of women randomized each month who were using HT was calculated. The trend in HT use was assessed with reference to the publication of the Women's Health Initiative interim results (July 2002), the Million Women Study (August 2003), and advice from the UK Committee on Safety of Medicines (December 2003). RESULTS: The median number of women recruited and randomized per month was 3,955 (mean 3,744). The proportion of randomized women using HT between April 2001 and June 2002 was 29%. This was followed by a steady monthly decline, and by February to September 2005, only 10% to 11% of newly recruited women were using HT. This trend was present in all age groups. However, in current users, the average duration of HT use remained steady at 10 to 11 years. CONCLUSIONS: There was a steady decline in HT use among postmenopausal women at recruitment into the United Kingdom Collaborative Trial of Ovarian Cancer Screening between April 2001 and September 2005. This is likely to reflect general trends in the UK population and is probably related to the premature closure of the large HT trials and the ensuing publicity.

Significant developments in occupational health and safety in Australia's construction industry.

Construction is Australia's third most dangerous industry. On average, 49 building and construction workers have been killed at work each year since 1997-1998. Securing safer construction workplaces is jeopardized by an Australian government bent on removing union influence. Workers must prove their individual health and safety is at risk or face fines of up to $22,000 over work stoppages. The Australian Chamber of Commerce and Industry view is that occupational health and safety (OHS) legislation is overly complex and biased unfairly against the employer. Significant advances in OHS achieved by construction unions working together with employers and government authorities are now at risk, to the detriment of workers.

Anticipated health behaviour changes and perceived control in response to disclosure of genetic risk of breast and ovarian cancer: a quantitative survey study among women in the UK.

BACKGROUND: Genetic risk assessment for breast cancer and ovarian cancer (BCOC) is expected to make major inroads into mainstream clinical practice. It is important to evaluate the potential impact on women ahead of its implementation in order to maximise health benefits, as predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure. OBJECTIVE: To examine anticipated health behaviour changes and perceived control to disclosure of genetic risk for BCOC and establish demographic and person-specific correlates of adverse anticipated responses in a population-based sample of women. DESIGN: Cross-sectional quantitative survey study carried out by the UK Office for National Statistics in January and March 2014. SETTING: Face-to-face computer-assisted interviews conducted by trained researchers in participants' homes. PARTICIPANTS: 837 women randomly chosen from households across the UK identified from the Royal Mail's Postcode Address File. OUTCOME MEASURES: Anticipated health behaviour change and perceived control to disclosure of BCOC risk. RESULTS: In response to a genetic test result, most women (72%) indicated 'I would try harder to have a healthy lifestyle', and over half (55%) felt 'it would give me more control over my life'. These associations were independent of demographic factors or perceived risk of BCOC in Bonferroni-corrected multivariate analyses. However, a minority of women (14%) felt 'it isn't worth making lifestyle changes' and that 'I would feel less free to make choices in my life' (16%) in response to BCOC risk disclosure. The former belief was more likely to be held by women who were educated below university degree level (P<0.001) after adjusting for other demographic and person-specific correlates. CONCLUSION: These findings indicate that women in the UK largely anticipate that they would engage in positive health behaviour changes in response to BCOC risk disclosure.

Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study.

Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09). Conclusion ROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women.

Aberrant regulation of RANKL/OPG in women at high risk of developing breast cancer.

Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime in North America and Europe. Receptor Activator of NF-kB Ligand (RANKL), its receptor RANK and the natural antagonist osteoprotegerin (OPG) are essential regulators of bone resorption. We have initially shown that RANKL/RANK are essential for hormone-driven mammary epithelial proliferation in pregnancy and RANKL/RANK have been implicated in mammary stem cell biology. Using genetic mouse-models, we and others identified the RANKL/RANK system as a key regulator of sex hormone, BRCA1-mutation, and oncogene-driven breast cancer and we proposed that RANKL/RANK might be involved in the initiation of breast tumors. We now report that in postmenopausal women without known genetic predisposition, high RANKL and progesterone serum levels stratify a subpopulation of women at high risk of developing breast cancer 12-24 months before diagnosis (5.33-fold risk, 95%CI 1.5-25.4; P=0.02). In women with established breast cancer, we demonstrate that RANKL/OPG ratios change dependent on the presence of circulating tumor cells (CTCs). Finally, we show in a prospective human breast cancer cohort that alterations in RANKL/OPG ratios are significantly associated with breast cancer manifestation. These data indicate that the RANKL/RANK/OPG system is deregulated in post-menopausal women at high risk for breast cancer and in women with circulating tumor cells. Thus, serum levels of RANKL/OPG are potentially indicative of predisposition and progression of breast cancer in humans. Advancement of our findings towards clinical application awaits prior validation in independent patient cohorts.

Population-based genetic risk prediction and stratification for ovarian cancer: views from women at high risk.

There is an opportunity to improve outcomes for ovarian cancer (OC) through advances in risk stratification, early detection and diagnosis. A population-based OC genetic risk prediction and stratification program is being developed. A previous focus group study with individuals from the general population showed support for the proposed program. This qualitative interview study explores the attitudes of women at high risk of OC. Eight women participated in one-on-one, in-depth, semi-structured interviews to explore: experiences of learning of OC risk, risk perceptions, OC knowledge and awareness, and opinions on risk stratification approach. There was evidence of strong support for the proposed program. Benefits were seen as providing reassurance to women at low risk, and reducing worry in women at high risk through appropriate clinical management. Stratification into 'low' and 'high' risk groups was well-received. Participants were more hesitant about stratification to the 'intermediate' risk group. The data suggest formats to effectively communicate OC risk estimates will require careful thought. Interactions with GPs were highlighted as a barrier to OC risk assessment and diagnosis. These results are encouraging for the possible introduction and uptake of a risk prediction and stratification program for OC in the general population.

Use and perceived efficacy of complementary and alternative medicines after discontinuation of hormone therapy: a nested United Kingdom Collaborative Trial of Ovarian Cancer Screening cohort study.

OBJECTIVE: Given that the Women's Health Initiative reported in 2002 increased risks of breast cancer and cardiovascular events with hormone therapy (HT) use and many women discontinued use, we assessed the use and perceived efficacy of complementary and alternative medicines (CAMs) for menopausal symptom relief after discontinuation of HT. METHODS: Postmenopausal women aged 50 to 65 years within the United Kingdom Collaborative Trial of Ovarian Cancer Screening who were willing to take part in a secondary study were mailed a survey to evaluate menopausal symptom management. Use and perceived efficacy of CAMs for relief of vasomotor symptoms (VMS) upon discontinuation of HT were examined. RESULTS: The survey was sent to 15,000 women between July 2 and July 9, 2008. Seventy-one percent (10,662 of 15,000) responded, and 10,607 women with complete data were included. Ever use of HT was reported by 60.2% (6,383 of 10,607). At survey completion, 79.3% (5,060 of 6,383) had discontinued HT, with 89.7% (4,540 of 5,060) of the latter reporting using one or more CAMs for VMS relief. About 70.4% (3,561 of 5,060) used herbal remedies, with evening primrose oil (48.6%; 2,205 of 4,540) and black cohosh (30.3%;1,377 of 4,540) being most commonly used. Exercise was used by 68.2% (3,098 of 4,540), whereas other behavioral/lifestyle approaches were less frequently reported (13.9%; 629 of 4,540). Contrarily, more women (57%-72%) rated behavioral/lifestyle approaches as effective compared with herbal remedies (28%-46%; rating ≥4 on a "helpfulness" scale from 1-10). Among medical treatments, selective serotonin reuptake inhibitors were used by 10% and rated effective by 72.1%. CONCLUSIONS: Although more women use over-the-counter medicines, behavioral/lifestyle approaches seem to provide better relief of VMS. There is a pressing need for better evidence-based lay information to support decision-making on CAM use for relief of VMS.

Adjusting the frequency of mammography screening on the basis of genetic risk: Attitudes among women in the UK.

PURPOSE: To explore public attitudes towards modifying frequency of mammography screening based on genetic risk. METHODS: Home-based interviews were carried out with a population-based sample of 942 women aged 18-74 years in the UK. Demographic characteristics and perceived breast cancer (BC) risk were examined as predictors of support for risk-stratified BC screening and of the acceptability of raised or lowered screening frequency based on genetic risk, using multivariate logistic regression. RESULTS: Over two-thirds of respondents (65.8%) supported the idea of varying screening frequency on the basis of genetic risk. The majority (85.4%) were willing to have more frequent breast screening if they were found to be at higher risk, but fewer (58.8%) were willing to have less frequent screening if at lower risk (t (956) = 15.6, p < 0.001). Ethnic minority status was associated with less acceptability of more frequent screening (OR = 0.40, 95% CI = 0.21-0.74), but there were no other significant demographic correlates. Higher perceived risk of BC was associated with greater acceptability of more frequent screening (OR = 1.71, 95%CI = 1.27-2.30). CONCLUSION: Women were positive about adjusting the frequency of mammography screening in line with personal genetic risk, but it will be important to develop effective communication materials to minimise resistance to reducing screening frequency for those at lower genetic risk.