Abstract: Guidelines endorse the use of chemoprevention for breast cancer risk reduction. This study examined the barriers and facilitators to chemoprevention use for Australian women at increased risk of breast cancer, and their clinicians. Surveys, based on the Theoretical Domains Framework, were mailed to 1,113 women at ≥16% lifetime risk of breast cancer who were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer cohort study (kConFab), and their 524 treating clinicians. Seven hundred twenty-five women (65%) and 221 (42%) clinicians responded. Only 10 (1.4%) kConFab women had ever taken chemoprevention. Three hundred seventy-eight (52%) kConFab women, two (3%) breast surgeons, and 51 (35%) family physicians were not aware of chemoprevention. For women, the strongest barriers to chemoprevention were side effects (31%) and inadequate information (23%), which operate in the Theoretical Domains Framework domains of “beliefs about consequences” and “knowledge,” respectively. Strongest facilitators related to tamoxifen's long-term efficacy (35%, “knowledge,” “beliefs about consequences,” and “goals” domains), staying healthy for family (13%, “social role” and “goals” domains), and abnormal breast biopsy (13%, “environmental context” domain). The strongest barrier for family physicians was insufficient knowledge (45%, “knowledge” domain) and for breast surgeons was medication side effects (40%, “beliefs about consequences” domain). The strongest facilitators for both clinician groups related to clear guidelines, strong family history, and better tools to select patients (“environmental context and resources” domain). Clinician knowledge and resources, and beliefs about the side-effect consequences of chemoprevention, are key domains that could be targeted to potentially enhance uptake. Prevention Relevance: Despite its efficacy in reducing breast cancer incidence, chemoprevention is underutilised. This survey study of Australian women and their clinicians used behavioural change theory to identify modifiable barriers to chemoprevention uptake, and to suggest interventions such as policy change, educational resources and public campaigns, that may increase awareness and use. See related Spotlight by Vogel, p. 1

Abstract: Background: It is anticipated that cancer risk prediction tools, including those with genomic risk information, will increasingly be used to communicate personalised cancer risk to the public. Receiving information on personal genomic risk of cancer might encourage conversations about cancer prevention and early detection with family, friends and health professionals, but few studies have examined this. Aims: To explore participant communication about personal genomic risk of melanoma to family, friends and health professionals, using a mixed-methods approach, and to examine results according to participants' genomic risk category (low, average, high). Methods: We conducted a study examining the impact of giving information on personalised genomic risk of melanoma to the public. Participants (n=101) received a personalised booklet presenting their melanoma genomic risk based on variants in 21 genes, together with telephone-based genetic counselling and generic educational materials. They completed a questionnaire 3-months after receiving their personal genomic risk of melanoma. To further contextualise these data, we conducted semi-structured qualitative interviews with 30 participants. Results: Participants' communication with health professionals according to melanoma genomic risk category was 41% for high-risk, 16% for average-risk and 13% for low-risk (P=0.02). Communication with family was 83% for high-risk, 65% for average-risk, 79% for low-risk participants (P=0.19); and communication with friends was 55% for high-risk, 43% for average-risk, 54% for low-risk participants (P=0.49). Preliminary thematic analysis found that preventive behaviours and early detection were raised by participants in discussions with family and doctors. Reasons for not communicating genomic risk included: concern about causing worry and not feeling a need to share the information. Conclusions: Genomic risk information prompted conversations about melanoma risk and prevention, most frequently with family. When stratified by genomic risk, comparable numbers of participants discussed their genomic risk with family and friends, but communication with health professionals was more frequent among participants in a high-risk category. Citation Format: Anne E. Cust, Amelia K. Smit, David Espinoza, Keogh Louise, Phyllis N. Butow, Kate Dunlop, Judy Kirk, Ainsley J. Newson. Communicating information about personalised genomic risk of melanoma to family, friends, and health professionals. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B15.

Abstract: Research on the utilization of genetic testing services for mutations in BRCA1 and BRCA2 has focused on women with a strong family history of breast and ovarian cancer. We conducted a population-based case-control-family study of Australian women diagnosed with invasive breast cancer before age 40 years, unselected for family history, and tested for germ line mutations in BRCA1 and BRCA2. Case subjects found to carry a deleterious mutation and their relatives who had given a research blood sample were informed by mail that the study had identified “genetic information” and were offered the opportunity to learn more. Those interested were referred to a government-funded family cancer clinic. Of 94 subjects who received the letter, 3 (3%) did not respond and 38 (40%) declined to learn their result (16 declined the referral, 10 accepted but did not attend a clinic, and 12 attended a clinic but declined testing), and 12 (13%) remain “on hold.” The remaining 41 (44%) chose to learn their result (3 of whom already knew their mutation status). There was no evidence that the decision to learn of mutation status depended on age, gender, family history, or having been diagnosed with breast cancer. Of 19 families with more than one participant, in 11 (58%) there was discordance between relatives in receiving genetic results. Although in Australia genetic testing is offered free of charge and insurance issues are not a major consideration, we found considerable reluctance, indecision, and unexplained variability both between and within case families in the desire to know their mutation status.

Abstract: Background Toxicity data are routinely collected in phase 3 (neo)adjuvant breast cancer (BC) clinical trials, but ovarian toxicity is infrequently assessed, despite its impact on fertility and long-term health. Thus, little is known about the ovarian effects of newer BC therapies. This results in an information gap for women when making treatment decisions. We explored the barriers to collecting ovarian toxicity data and/or including ovarian function as an endpoint in BC trials of anti-cancer drugs. Methods Semi structured interviews were conducted with key stakeholders involved in BC clinical trials (clinicians, consumers, pharmaceutical companies, drug regulatory advisors). Participants were asked detailed questions about how trial endpoints are selected, whether effects on the ovary are assessed, and barriers to and benefits of collecting ovarian function data to assess ovarian toxicity. Interviews were transcribed verbatim, coded in NVivo software and analysed using inductive thematic analysis. Results Saturation was reached after 25 interviews (9 clinicians, 7 consumers, 5 drug regulatory advisors, 4 pharmaceutical company advisors); half were female. Participants were from North America (20%), Europe (52%), Australia (24%), Asia (4%). Median age was 50 years and median time in breast cancer research or drug regulation was 16 years. The main reported barrier to the collection of ovarian toxicity data in clinical trials was that this issue was rarely considered. Reasons included that these data are considered less important than survival data and are not required for regulatory approval. Other barriers included limited resources, lack of knowledge regarding how to assess ovarian side effects and lack of relevance in certain settings (further detail in Table 1). Most participants believed assessing ovarian toxicity in trials would be beneficial to clinicians and to patients (eg. assisting treatment and family planning decisions). Strategies to increase ovarian toxicity assessment included its inclusion in clinical trial design guidelines, improving familiarity with ovarian function markers among trial design decision makers, and increased stakeholder interest. A stronger consumer voice and regulatory and clinician advocacy were regarded as important. Regarding trial endpoint selection, pharmaceutical companies were almost always identified as the main decision maker, but clinicians including cooperative trial group researchers, consumers, regulators, and statisticians were also important contributors. While most consumers and pharmaceutical company advisors felt clinicians and consumers influenced trial design, in contrast, some clinicians and regulators reported consumers and clinicians had little influence. Factors identified as important considerations in determining trial endpoints included the main goal of the trial (eg. regulatory approval), established standardised endpoints, resources, and the investigational agent studied. All pharmaceutical advisors reported that meeting the requirements for regulatory approval was the major factor considered during endpoint selection. Conclusion This qualitative analysis evaluates the barriers to including measures of ovarian function in BC clinical trials. Increased awareness, stronger advocacy and guidelines might lead to more frequent inclusion of this important endpoint in future trials that include premenopausal women with early BC. Table 1.Emergent themes regarding ovarian toxicity assessment in BC trialsThemeDomainCategory 1: Barriers to assessment of ovarian function Not prioritisedNot discussed or thought about;Not the primary question studied by clinical trial;Less important than other endpoints/data;Not required for regulatory approval;Data not related to survival is infrequently published;More appropriate for a follow up/registry studyToo resource intensive A burden on investigators and patients;Difficult to collect good quality data;Assessment not considered feasible;Time to obtaining results too long;Too costlyLack of knowledgeLack of clinician knowledge regarding ovarian function side effects;Lack of consensus regarding which markers to assess;Lack of preclinical data suggestive of ovarian toxicityData not relevant in certain settingsConcurrent use of gonadotoxic chemotherapy;Trials mandate contraception use;Want to suppress ovarian function in some breast cancer phenotypes;Low numbers of premenopausal women enrolled;Investigational agent already known to cause ovarian toxicity/suppressionCategory 2: Perceived benefits of assessing ovarian function Data important to patientsImproved ability to make informed cancer treatment decisions;Improved ability to make fertility and ovarian preservation decisions;Infertility and early menopause are relevant and important to patients;Preservation of ovarian function is important for quality of life;To avoid potential harm to patientsData important to cliniciansImproved ability to counsel patients;Improved understanding of the investigational agent;Improved understanding of the impact of ovarian function on disease outcomes;Holistic understanding of a patient’s experience on treatment;Prospective information is more robust than retrospective dataCategory 3: Strategies to improve inclusionIncreased stakeholder interestIncreased clinician advocacy;Increased consumer voice;Increased regulatory buy in;Increased cooperative trial group interest;Increased reproductive specialist involvement;Increased pharmaceutical company interestIncreased awareness regarding ovarian function and onco-fertilityTrial design guidelines and recommendations;Increased discussion and education;Improved familiarity with ovarian markers and ease of incorporation/collection;Use of social media and internet resources Citation Format: Wanyuan Cui, Kelly-Anne Phillips, Prudence A Francis, Sherene Loi, Richard A Anderson, Ann H Partridge, Louise A Keogh. What are the barriers to assessment of ovarian toxicity in breast cancer clinical trials? [abstract] . In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-19-03.

Abstract: Background: Communication of personalized melanoma genomic risk information may improve melanoma prevention behaviors. Methods: We evaluated the feasibility and acceptability of communicating personalized genomic risk of melanoma to the public and its preliminary impact on behaviors and psychosocial outcomes. One hundred eighteen people aged 22 to 69 years provided a saliva sample and were randomized to the control (nonpersonalized educational materials) or intervention (personalized booklet presenting melanoma genomic risk as absolute and relative risks and a risk category based on variants in 21 genes, telephone-based genetic counseling, and nonpersonalized educational materials). Intention-to-treat analyses overall and by-risk category were conducted using ANCOVA adjusted for baseline values. Results: Consent to participate was 41%, 99% were successfully genotyped, and 92% completed 3-month follow-up. Intervention participants reported high satisfaction with the personalized booklet (mean = 8.6, SD = 1.6; on a 0–10 scale) and genetic counseling (mean = 8.1, SD = 2.2). No significant behavioral effects at 3-month follow-up were identified between intervention and control groups overall: objectively measured standard erythemal doses per day [−16%; 95% confidence interval (CI), −43% to 24%] and sun protection index (0.05; 95% CI, −0.07 to 0.18). There was increased confidence identifying melanoma at 3 months (0.40; 95% CI, 0.10–0.69). Stratified by risk category, effect sizes for intentional tanning and some individual sun protection items appeared stronger for the average-risk group. There were no appreciable group differences in skin cancer–related worry or psychologic distress. Conclusions: Our results demonstrate feasibility and acceptability of providing personalized genomic risk of melanoma to the public. Impact: Genomic risk information has potential as a melanoma prevention strategy. Cancer Epidemiol Biomarkers Prev; 26(2); 212–21. ©2016 AACR.