ANZCTR - Registration

Registration number

ACTRN12617000594325

Ethics application status

Approved

Date submitted

19/04/2017

Date registered

27/04/2017

Date last updated

11/03/2019

Date data sharing statement initially provided

11/03/2019

Date results information initially provided

11/03/2019

Type of registration

Retrospectively registered

Titles & IDs

Public title

Psychosocial Aspects of Genomic Testing for Breast Cancer Risk

Scientific title

Psychosocial aspects of genomic testing for breast cancer risk among with a high risk family history of breast cancer.

Secondary ID [1]

RG 15-22

Universal Trial Number (UTN)

U1111-1195-4653

Trial acronym

Linked study record

The parent study, ViP, aims to investigate the role of genomic variants in women at high risk of breast cancer. As such it is not registered clinical trial.

The study ethics number is: HREC/11/PMCC/43

Reference publication: Sawyer S, Mitchell G, McKinley J, Chenevix-Trench G, Beesley J, Chen XQ, Bowtell D, Trainer AH, Harris M, Lindeman GJ, James PA. A role for common genomic variants in the assessment of familial breast cancer. J Clin Oncol. 2012 Dec 10;30(35):4330-6.

Health condition

Health condition(s) or problem(s) studied:

breast cancer

Condition category

Condition code

Mental Health

Studies of normal psychology, cognitive function and behaviour

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study aims to assess the psychological and behavioural outcomes associated with receiving personal polygenic breast cancer risk results.

Intervention: uptake of polygenic breast cancer risk results.

Participants in this study will be invited by letter to take part in the study and receive their personal polygenic breast cancer risk result. The invitation packet includes: a study invitation letter, participant information and consent form, and an educational leaflet describing polygenic risk. The leaflet has been pilot tested in a previous study.

Participants have undergone genomic testing and had their individual polygenic risk score (PRS) calculated as part of the parent ViP study. Participants recruited to the ViP study have provided blood samples either through a Familial Cancer Clinic (index cases) or collected at their local pathology collection center (family members recruited through index cases). Individual PRS was calculated based on 64 common risk variants. PRS is a log-additive score, calculated by weighing each risk variant by the log of the per-allele odds ratio as measured in this cohort. For further information on this please see Sawyer, et al. 2012, J. Clin. Oncol.

Participants who opt to receive their results will attend a one-off, face to face appointment of approximately 1 hour, with a qualified genetic counsellor and/or a clinical geneticist at one of the six participating familial cancer clinics. These sites include: Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Austin Health, Monash Health, Cabrini Hospital, and the Royal Hobart Hospital.

The intervention received will be personalized to the participant. This is because participants are receiving their own personal polygenic risk. Furthermore, each participant has their own unique personal and family history of breast cancer which influences their individual breast cancer risk assessment. Therefore, any discussion of breast cancer risk and risk management strategies will be personalised in accordance to the individual’s polygenic risk result, and personal/family history of breast cancer.

As polygenic information represents a new test in the familial cancer setting, genetic health professionals participating in the study have completed training on the return of this information. The training has included a one day workshop which covered education on polygenic risk, its implications for breast cancer risk prediction, and methods of communicating polygenic risk results. The workshop was developed by A/Prof. Paul James (clinical geneticists and ViP study principal investigator), Ms Mary Anne-Young (senior genetic counsellor Peter MacCallum Cancer Centre) and A/Prof. Kristine Barlow Stewart (Director, Masters of Genetic Counselling University of Sydney). Genetic health professionals also have the opportunity to observe senior clinicians (A/Prof James and Ms Young) return PRS results to study participants. A training manual and visual aids have also been developed to facilitate patient communication. Finally, a sample report has been developed based on a previous qualitative study.

Intervention code [1]

Prevention

Intervention code [2]

Lifestyle

Intervention code [3]

Behaviour

Comparator / control treatment

Psychological and behavioural outcomes will be compared between participants who opt to receive their PRS results (receivers) and those who opt not to receive their results (decliners)

Psychological and behavioural outcomes will also be compared based on personal history of breast cancer (affected or unaffected) and individual PRS results (high or low), such that four groups will be compared:
1) Affected high PRS
2) Affected low PRS
3) Unaffected high PRS
4) Unaffected low PRS

Control group

Active

Outcomes

Primary outcome [1]

M9: Breast cancer specific anxiety: will be assessed by the Impact of Events Scale

Timepoint [1]

For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)

Secondary outcome [1]

M2: Intention to receive results - single question to assess intention to receive their personal polygenic risk result

Timepoint [1]

Q1 - Baseline

Secondary outcome [2]

M3: Perceived breast cancer severity severity – will be assessed with one item adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.

Timepoint [2]

Q1 - Baseline

Secondary outcome [3]

M4: Perceived risk – will be assessed with three items adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.

Timepoint [3]

For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)

Secondary outcome [4]

M5: Response efficacy (perceived benefits of receiving results) – will be assessed using six items have been adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.

Timepoint [4]

Q1 - Baseline

Secondary outcome [5]

M6: Response cost (perceived barriers to receiving results ) – will be assessed using six adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.

Timepoint [5]

Q1 - Baseline

Secondary outcome [6]

M7: Self-efficacy (confidence in receiving results despite ‘obstacles’ – will be measured with seven items adapted from Fisher, et al., (2012) Preventive Medicine, 55: p. 514-520.

Timepoint [6]

Q1 - Baseline

Secondary outcome [7]

M8: Uncertainty avoidance – will be assessed using Attitudes Towards Uncertainty scale

Timepoint [7]

Q1 - Baseline

Secondary outcome [8]

M10: Anxiety and Depression – will be assessed using the Hospital Anxiety and Depression Scale (HADS)

Timepoint [8]

For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)

Secondary outcome [9]

M11: Knowledge – 10 true-false questions have been developed to assess knowledge of polygenic risk and familial breast cancer.

Timepoint [9]

For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)

Secondary outcome [10]

M12: Stressful life events: will be assessed using the List of Threatening Experiences. Threatening life events may affect anxiety and distress levels and will be measured as potential confounding variable.

Timepoint [10]

Q1 - Baseline

Secondary outcome [11]

M13: Concordance with screening guidelines – will be assessed in accordance with the Australian national guidelines for mammography and clinical breast examination

Timepoint [11]

This will be measured at baseline (Q1) and 12 month follow up (Q3) for all participants

Secondary outcome [12]

M14: Intention to take up and actual uptake of preventative strategies – participants are asked whether they have undertaken risk reducing strategies including risk reducing surgery (surgery (bilateral mastectomy), and medication (i.e. tamoxifen and raloxifen). Responses include, "Yes", "No", and "No but I am planning to". For participants who indicate they plan to undertake a particular strategy, they are also ask asked indicate whether they plan to commence this strategy in the next 12 months.

Participants are also asked about lifestyle factors associated with breast cancer risk including, weigh and height (BMI), weekly alcohol consumption and weekly, and amount of moderate/intense exercise in a week.

Timepoint [12]

For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)

Secondary outcome [13]

M16: Regret over the decision – will be assessed using the Decision Regret Scale.

Timepoint [13]

For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured 12 months after consenting to the study (Q3)

Secondary outcome [14]

M17: Test related distress, positive experience and uncertainty- will be assessed using The multidimensional impact of cancer risk assessment

Timepoint [14]

For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured 12 months after consenting to the study (Q3)

Secondary outcome [15]

M18: Recall and interpretation of testing results – 3 items have been developed to assess recall and understanding of testing results.

Timepoint [15]

For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

Secondary outcome [16]

M19: Reasons for declining results – will be measured with 15 items adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.

Timepoint [16]

For participants who opted not to receive their results this will be measured 12 months after consenting to the study (Q3)

Secondary outcome [17]

M15. Satisfaction with Information Provided – participants will be asked to indicate how satisfied they were with the information provided by the genetic counsellor or geneticist at their results appointment on a 5 point Likert scale, with responses ranging from “very satisfied” (1) through to “very dissatisfied” (5). They will also be required to indicate whether the amount information received was “too much”, “about right” or “too little” and whether the language used was “too complicated”, “about right” or “too simple”.

Timepoint [17]

For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2

Eligibility

Key inclusion criteria

Women enrolled in the ‘Variants in Practice’ study (ViP) provide a unique cohort in which to systematically ascertain the important psychosocial and clinical implications of genomic testing. The ViP study (HREC/11/PMCC/43) is enrolling a cohort of over 4,000 Victorian women and men who have a high-risk family history of breast cancer, that includes index cases with a personal history of breast cancer and their affected and unaffected relatives

Inclusion criteria: Women aged 18 years and over who are current participants of the ViP study. Additional criteria includes women where a known breast cancer predisposition gene has been excluded as the cause of their personal and/or familial breast cancer risk, and who are sufficiently proficient in English to provide informed consent and complete questionnaires.

Both index cases with a personal history of breast cancer, and their family members (affected and unaffected) will be invited to participate in this psychosocial study. This study will include women with a low (N=200) and high (N=200) polygenic risk score. Each group will then stratified by disease status, such that about 100 affected and 100 unaffected women are included in each study group.

Minimum age

18 Years

Maximum age

No limit

Sex

Females

Can healthy volunteers participate?

No

Key exclusion criteria

- Women where a known breast cancer predisposition gene mutation (e.g. BRCA1/2) has been identified as the cause of their personal and/or familial breast cancer
- male participants of the ViP study. Men will be excluded as they constitute a very small proportion of ViP participants (<10%) and therefore as the small sample size will preclude a meaningful statistical comparison with the majority female cohort.
- Women who receive an intermediate polygenic risk score will also be ineligible, because intermediate results do not change a woman’s risk status and hence risk management advice in a clinically meaningful way.
- The funding parameters for this project means that it is not feasible to develop the study documentation and the assessment tools in multiple languages. Hence, women must be able to complete English language self-administered questionnaires to be eligible to participate in the study.
- Patients with obvious intellectual or mental impairment that may interfere with the patient's ability to understand the requirements of the study will also be excluded.

Study design

Statistical methods / analysis

Sample size calculation: Based on similar previous studies (Kasparian et al, 2009), a sample size of 400 women is required to have 320 women completing the study with 215 receivers and 105 decliners (after adjusting for loss to follow up of approximately 20%). For a two sided test and based on a 5% significance level, this sample size will have 80% power to detect a clinically meaningful difference in the primary psychological outcome of breast cancer anxiety as measured by the Impact Event Scale (SD 14.2, range 0-75 scores) at the 2-week follow-up, between affected and unaffected women who receive a high PRS result (hypothesis 2c). A difference of seven scores (half a standard deviation) on the IES is considered a clinically meaningful difference to detect (Norman et al, 2003, Med Care).

Data analysis:
Data will be analysed using the SPSS program. Basic descriptive statistics, including means, medians, percentages, ranges and standard deviations will be calculated to describe the sample in terms of socio-demographic characteristics. The means of baseline key variables (M3 to M11) will be compared between receivers and decliners using independent samples t-test. Categorical data will be analysed by X2 test or Fisher’s exact test, as appropriate, whereas Student’s t-test for independent samples will be applied for continuous variables. Paired samples t–test will be applied to paired data of the baseline and follow up questionnaires. Equivalent non-parametric tests will used to analyse non-normally distributed data.

For each of the main outcome variables (M9 to M15), linear or logistic regression shall be used as appropriate. Further multivariate analyses will be used to adjust for potential confounding variables (e.g. age, parity, income). Appropriate regressions will be performed to investigate whether outcomes differ between receivers and decliners (hypothesis 1a) and between subgroups of affected and unaffected women (2c) and those receiving either a low or a high PRS (2a.ii). Repeated measurements will be analysed using linear mixed models to assess how outcomes change over time amongst receivers (hypothesis 2a.i and 2b). This approach adjusts for the repeated measures per person and also allows for missing values. Logistic mixed models will be used if there is a need to dichotomise an outcome variable. Correlations between women in the same family cluster will also be adjusted via mixed models.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

Actual

3/08/2016

Date of last participant enrolment

Anticipated

1/06/2018

Actual

24/09/2018

Date of last data collection

Anticipated

1/11/2019

Actual

Sample size

Target

320

Accrual to date

Final

217

Recruitment in Australia

Recruitment state(s)

TAS,VIC

Recruitment hospital [1]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [2]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [3]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [4]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [5]

Cabrini Hospital - Malvern - Malvern

Recruitment hospital [6]

Royal Hobart Hospital - Hobart

Recruitment postcode(s) [1]

3000 - Melbourne

Recruitment postcode(s) [2]

3050 - Parkville

Recruitment postcode(s) [3]

3084 - Heidelberg

Recruitment postcode(s) [4]

3168 - Clayton

Recruitment postcode(s) [5]

3144 - Malvern

Recruitment postcode(s) [6]

7000 - Hobart

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Cancer Council NSW

Country [1]

Australia

Primary sponsor type

Individual

Name

Prof. Bettina Meiser, UNSW Sydney

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Tatiane Yanes

Country [1]

Australia

Other collaborator category [1]

Individual

Name [1]

A/Prof Paul James

Country [1]

Australia

Other collaborator category [2]

Individual

Name [2]

Ms Mary-Anne Young

Country [2]

Australia

Other collaborator category [3]

Individual

Name [3]

A/Prof. Kristine Barlow-Stewart

Country [3]

Australia

Other collaborator category [4]

Individual

Name [4]

Dr Tony Roscioli

Country [4]

Australia

Other collaborator category [5]

Individual

Name [5]

Prof Jane Halliday

Country [5]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Peter McCallum Cancer Center Human Research Ethics Committee

Ethics committee address [1]

305 Grattan St, Melbourne VIC 3000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/01/2016

Approval date [1]

09/06/2016

Ethics approval number [1]

HREC/16/PMCC/2

Ethics committee name [2]

Tasmania Health and Medical HREC

Ethics committee address [2]

301 Sandy Bay Road, Sandy Bay, Hobart, TAS 7001

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

01/03/2017

Approval date [2]

06/04/2017

Ethics approval number [2]

H0016395

Summary

Brief summary

What is this study for?
This study aims to assess the psychological and behavioral outcomes associated with offering women their personal polygenic risk score for breast cancer risk. The study will include women who opt to receive their results as well, as those who decline this offer.

Who is it for?
You may be eligible to participate in this trial if you are a woman aged 18 or over who has already enrolled in the 'Variants in Practice’ study (ViP) in whom known breast cancer predisposition genes have been excluded as the cause of your personal and/or familial breast cancer risk.

Study details:
Participants enrolled in this trial will have a personal polygenic risk score (PRS). Individual PRS result has been calculated as part of the parent study “Variants in Practice”. Participants who opt to receive the results will then attend a one hour face-to-face session with a clinical geneticist or genetic counsellor who has received training in delivering these results. During this session, the risk score will be discussed as well as any preventative strategies which may be considered. Participants can also opt to not receive their results, in which case they will not receive this face-to-face session. All participants will be asked to complete a number of questionnaires assessing the psychological effects of receiving or not receiving their risk score.

It is hoped that the findings from this trial will help to develop a model of care offering polygenic breast cancer risk testing, in which results are provided to participants without causing negative psychological effects such as breast cancer anxiety and depression.

Trial website

Public notes

Attachments [1]

/AnzctrAttachments/372743-Appendix A _Protocol V5_09.11.2016_clean.docx (Protocol)

Attachments [2]

/AnzctrAttachments/372743-16_10 Ethical Approval Certificate_9June2016.pdf (Ethics approval)

Attachments [3]

/AnzctrAttachments/372743-Appendix G_PICF V4_11.11.2016_clean.docx (Participant information/consent)

Attachments [4]

/AnzctrAttachments/372743-Appendix I_Educational Pamphlet V2_29.03.2016.pdf (Supplementary information)

Contacts

Principal investigator

Name

Prof Bettina Meiser

Address

Psychosocial Research Group,
Prince of Wales Clinical School,
Level 4 Lowy Cancer Research Centre
UNSW Sydney
NSW 2052

Country

Australia

Phone

+61 (2) 9385 0025

Email

[email protected]

Contact person for public queries

Name

Ms Tatiane Yanes

Address

Psychosocial Research Group,
Prince of Wales Clinical School,
Level 4 Lowy Cancer Research Centre
UNSW Sydney
NSW 2052

Country

Australia

Phone

+61 2 9385 0031

Email

[email protected]

Contact person for scientific queries

Name

Ms Tatiane Yanes

Address

Psychosocial Research Group,
Prince of Wales Clinical School,
Level 4 Lowy Cancer Research Centre
UNSW Sydney
NSW 2052

Country

Australia

Phone

+61 2 9385 0031

Email

[email protected]

Trial Review

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Documents added automatically