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Trial registered on ANZCTR


Registration number
ACTRN12619001046190
Ethics application status
Approved
Date submitted
23/06/2019
Date registered
24/07/2019
Date last updated
24/07/2019
Date data sharing statement initially provided
24/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The metabolic effects of endocrine therapy in postmenopausal women with oestrogen-receptor-positive breast cancer
Scientific title
The metabolic effects of endocrine therapy in postmenopausal women with oestrogen-receptor-positive breast cancer
Secondary ID [1] 298363 0
None
Universal Trial Number (UTN)
U1111-1234-3914
Trial acronym
METABREAST
Linked study record
No

Health condition
Health condition(s) or problem(s) studied:
cardiovascular disease 313022 0
Breast cancer 313023 0
Menopause 313024 0
oestradiol depletion 313335 0
Condition category
Condition code
Cardiovascular 311533 311533 0 0
Coronary heart disease
Metabolic and Endocrine 311534 311534 0 0
Metabolic disorders
Cancer 311535 311535 0 0
Breast

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The arm of interest is those undergoing endocrine therapy (aromatase inhibitor or tamoxifen). Exposure must be continuous for the 12 months duration of the study.

All participants will be observed over 3 study visits and will be followed up over a total duration of 12 months for the evaluation of the primary outcomes. Although the primary timepoint for outcomes is at 12 months, this is a longitudinal study and data will continue to collected beyond 12 months up to 10 years.

*Baseline visit/visit 1: conducted either within 8 weeks prior to commencing endocrine therapy/within 8 weeks of having commenced endocrine therapy (for the arm of interest group) or within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology (for the control group).

-Consent to trial participation and consent to access to records
-Quality of life questionnaire
-Blood test
-Medical and physical assessment
-Fibroscan
-EndoPAT peripheral arterial tone measurement
-Total body composition and dual energy Xray absorptiometry scan
-Step count assessment via pedometer

*Visit 2: 6 months after baseline visit
-Quality of life questionnaire
-Blood test
-Medical and physical assessment
-Fibroscan (if baseline fibroscan showed evidence of fibrosis (>6kpa) or steatosis (CAP >300)
-EndoPAT peripheral arterial tone measurement
-Total body composition and dual energy Xray absorptiometry scan
-Step count assessment via pedometer

Visit 3: 12 months after baseline visit
-Quality of life questionnaire
-Blood test
-Medical and physical assessment
-Fibroscan
-EndoPAT peripheral arterial tone measurement
-Total body composition and dual energy Xray absorptiometry scan
-Step count assessment via pedometer

The dose, type and duration of endocrine therapy is personalised for each participant depending on their cancer type and stage, their comorbidities and risk factors, and their tolerance to side effects. This is a decision made between the treating oncologist and the patient in the oncology outpatients clinic. The oncologist tends to review treatment tolerance and response every 3 months. This is all part of routine care and would be happening regardless of enrolment in this study.
Intervention code [1] 314606 0
Not applicable
Comparator / control treatment
Controls will be postmenopausal, aged and body mass index- matched women with benign breast pathology (cysts, papilloma, micro calcifications), ductal carcinoma insitu, lobular carcinoma insitu or breast cancer not requiring endocrine treatment. Controls may be exposed to other treatments including radiotherapy and surgical interventions

All controls will be observed over 3 study visits and will be followed up over a total duration of 12 months. The 3 study visits will be identical to the arm of interest group.
Control group
Active

Outcomes
Primary outcome [1] 320458 0
Changes in visceral adipose tissue at 12 months in women on AROMATASE INHIBITOR therapy compared to controls (as measured by dual energy Xray absorptiometry).

Timepoint [1] 320458 0
The timepoint for assessing the primary outcome change in visceral adipose tissue will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo body composition scans (which includes evaluation of visceral adipose tissue) at baseline, 6 months and 12 months.

Although this primary outcome is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Primary outcome [2] 320459 0
Changes in subcutaneous adipose tissue at 12 months in women on AROMATASE INHIBITOR therapy compared to controls (as measured by dual energy Xray absorptiometry).
Timepoint [2] 320459 0
The timepoint for assessing the primary outcome of change in subcutaneous adipose tissue will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo body composition scans (which includes evaluation of subcutaneous adipose tissue) at baseline, 6 months and 12 months.

Although this primary outcome will be evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Primary outcome [3] 320709 0
Changes in total percentage body fat at 12 months in women on AROMATASE INHIBITOR therapy compared to controls (as measured by dual energy Xray absorptiometry).
Timepoint [3] 320709 0
The timepoint for assessing the primary outcome of change in total percentage body fat will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo body composition scans (which includes evaluation of total percentage body fat) at baseline, 6 months and 12 months.

Although this primary outcome will be evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [1] 371660 0
Changes in body composition (visceral adipose tissue, subcutaneous adipose tissue, total percentage body fat) at 12 months in women on TAMOXIFEN compared to controls (as measured by dual energy Xray absorptiometry)
Timepoint [1] 371660 0
The timepoint for assessing this secondary outcome - change in visceral adipose tissue, subcutaneous adipose tissue and total percentage body fat will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced tamoxifen therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the tamoxifen group and the controls undergo body composition scans (which includes evaluation of visceral adipose tissue, subcutaneous adipose tissue and total percentage body fat) at baseline, 6 months and 12 months.

Although this secondary endpoint is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [2] 371661 0
Changes in insulin resistance at 12 months in women on endocrine therapy compared to controls (as measured by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) which will be calculated from serum assay results for glucose, insulin and c peptide),
Timepoint [2] 371661 0
The timepoint for assessing the secondary outcome - insulin resistance will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo bloods evaluating bloods for fasting insulin, insulin and c peptide at baseline, 3 months, 6 months and 12 months.

Although this secondary outcome is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [3] 371662 0
Changes in lipid metabolism at 12 months in women on endocrine therapy compared to controls (as measured by fasting lipids)
Timepoint [3] 371662 0
The timepoint for assessing the secondary outcome - lipid metabolism will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo bloods evaluating fasting lipids at baseline, 3 months, 6 months and 12 months.

Although this secondary outcome is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [4] 371663 0
Changes in degree of hepatic steatosis at 12 months in women on endocrine therapy compared to controls (as measured by fibroscan)
Timepoint [4] 371663 0
The timepoint for assessing the secondary outcome - change in degree of hepatic steatosis will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo fibroscans at baseline and 12 months. Participants showing evidence of an abnormal fibroscan at baseline (either evidence of fibrosis >6kpa or steatosis CAP >300) will undergo an additional fibroscan at 6 months.

Although this secondary outcome will be evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [5] 371664 0
Changes in arterial wall health at 12 months in women on endocrine therapy compared to controls (as measured by peripheral arterial tone technology (EndoPAT)).
Timepoint [5] 371664 0
The timepoint for assessing the secondary outcome - change in peripheral arterial tone will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo EndoPAT at baseline, 6 months and 12 months.

Although this secondary end point is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [6] 371665 0
Changes in exercise levels at 12 months in women on endocrine therapy compared to controls (as measured by pedometer readings)
Timepoint [6] 371665 0
The timepoint for assessing this secondary outcome - change in exercise level will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group. .

Both the group of interest and the controls undergo exercise level monitoring (which includes measuring step count and distance walked via pedometers over 7 days) at baseline, 6 months and 12 months.

Although this secondary outcome will be evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [7] 372584 0
Changes in arterial wall calcification at 12 months in women on endocrine therapy compared to controls (as measured by abdominal aortic calcification scores).
Timepoint [7] 372584 0
The timepoint for assessing the secondary outcome - change in abdominal aortic calcification will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo dual energy Xray absorptiometry at baseline, 6 months and 12 months and a calcification score will be determined by an expert.

Although this secondary end point is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months for up to 10 years.
Secondary outcome [8] 372585 0
Changes in The Menopause-Specific quality of life Questionnaire score at 12 months in women on endocrine therapy compared to controls.
Timepoint [8] 372585 0
The timepoint for assessing the secondary outcome - change in quality of life will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo The Menopause-Specific Quality of Life Questionnaire (MENQOL) questionnaire at baseline, 6 months and 12 months.

Although this secondary end point is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months up to 10 years.
Secondary outcome [9] 372586 0
Changes in glucose metabolism at 12 months in women on endocrine therapy compared to controls (as measured by Haemoglobin A1c via serum assay).
Timepoint [9] 372586 0
The timepoint for assessing the secondary outcome -glucose metabolism will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo bloods evaluating Haemoglobin A1c, at baseline, 3 months, 6 months and 12 months.

Although this secondary outcome is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months up to 10 years.
Secondary outcome [10] 372587 0
Changes in adipokine levels at 12 months in women on endocrine therapy compared to controls (as measured by adiponectin and leptin levels via serum assays).
Timepoint [10] 372587 0
The timepoint for assessing the secondary outcome - changes in adipokine levels will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo bloods evaluating adiponectin and leptin levels, at baseline, 6 months and 12 months.

Although this secondary outcome is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months up to 10 years.
Secondary outcome [11] 372707 0
Changes in The Functional Assessment of Cancer Therapy- Breast cancer/Endocrine Subscale (FACT-ESv4) score at 12 months in women on endocrine therapy compared to controls.
Timepoint [11] 372707 0
The timepoint for assessing the secondary outcome - change in functionality will be at 12 months from the participants first/baseline study visit.

The first study visit must occur either within 8 weeks prior to commencing or within 8 weeks of having commenced endocrine therapy for the group of interest and within 8 weeks of the tissue diagnosis of breast cancer not requiring endocrine therapy/ductal carcinoma insitu/lobular carcinoma insitu/benign breast pathology for the control group.

Both the group of interest and the controls undergo The Functional Assessment of Cancer Therapy- Breast cancer/Endocrine Subscale (FACT-ESv4) questionnaire at baseline, 6 months and 12 months.

Although this secondary end point is evaluated at 12 months, ongoing longitudinal collection of data will continue beyond 12 months up to 10 years.

Eligibility
Key inclusion criteria
-Non-metastatic breast cancer
-Postmenopausal
-Aged 50-85yrs
-To commence endocrine therapy treatment intended for at least 12 months
-ECOG less than or equal to 1
-Ability to consent for study and comply with the study protocol requirements
Minimum age
50 Years
Maximum age
85 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
-Previous exposure to endocrine therapy (greater than 8 weeks prior to recruitment)
-If endocrine therapy stops or changes
-Established type 2 diabetes mellitus
-Continuous glucocorticoid therapy for less than or equal to 2 weeks within 6 months of study
-Hormone replacement therapy within 3 months of study
-Any disease which is likely to lead to serious illness or death within the study period

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
In studies reporting data on visceral adiposity in postmenopausal women using dual energy Xray absorptiometry and computed tomography, the standard deviation of patients’ visceral adiposity ranged between 15-100cm2 . For the primary endpoint of change in visceral adipose tissue, we consider a 25% difference a clinically significant difference. As such, to detect a 25% difference in visceral adipose tissue, assuming a standard deviation of 40cm2, a power of 80% and a two-sided significance level of 0.05, we will require recruitment of 40 participants in each study group. Factoring in a drop-out rate of 30%, we will require 100 participants in total (50 in each arm - aromatase inhibitor vs. controls).

In addition, we aim to recruit 30 patients receiving tamoxifen therapy for breast cancer so as to use this subset as a group with which to perform secondary endpoint analyses. Based on clinical experience and audit, this is the expected number of cases over the time course (18 months) of the recruitment phase of this study.

Longitudinal changes in the primary and secondary endpoints will be analyzed using paired-sample t-tests, generalised linear mixed models and generalised estimating equations and compared between patients with and without aromatase inhibitor therapy. Adjustments will be made for age, comorbidities and baseline measurements.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14013 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 26798 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 303071 0
Charities/Societies/Foundations
Name [1] 303071 0
Austin Medical Research Foundation
Address [1] 303071 0
145 Studley Rd, Heidelberg 3084, Victoria
Country [1] 303071 0
Australia
Primary sponsor type
Hospital
Name
The Department of Medicine, Austin Hospital
Address
145 Studley Rd, Heidelberg 3084, Victoria
Country
Australia
Secondary sponsor category [1] 303112 0
University
Name [1] 303112 0
The University of Melbourne
Address [1] 303112 0
Grattan St, Parkville 3010, Victoria
Country [1] 303112 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303475 0
Austin Health HREC
Ethics committee address [1] 303475 0
Office for Research, Austin Health
Level 8 HSB
Austin Hospital
145 Studley Rd, Heidelberg, 3084
Victoria
Ethics committee country [1] 303475 0
Australia
Date submitted for ethics approval [1] 303475 0
Approval date [1] 303475 0
07/02/2019
Ethics approval number [1] 303475 0
HREC/45582/Austin-2018

Summary
Brief summary
This study aims to evaluate the long term cardiovascular risk factors associated with taking endocrine therapies in patients with oestrogen receptor positive breast cancer.

Who is it for?

You may be eligible to join this study if you are aged 50-85 years (post-menopausal) and going to commence endocrine therapy treatment for breast cancer for at least 12 months,

Study details

The study will run for 12 months to observe the potential effects of endocrine treatment on cardiovascular risk factors. The study will involve 3 visits to determine changes in body fat distribution, and other markers of cardiovascular health. Part of the study will involve questionnaires, fasting blood tests, body, liver and bone density scans, There will be an additional blood test done between visits 1 and 3.

The results of this study will provide clinicians with a potential means of stratifying each breast cancer woman's cardiovascular risk, enabling delivery of personalised care. This project will also provide a platform for subsequent interventional studies to investigate the clinical impact of risk factor modification.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93778 0
Prof Mathis Grossmann
Address 93778 0
Austin Hospital
145 Studley Rd, Heidelberg
Vic 3084
Country 93778 0
Australia
Phone 93778 0
+61 3 94965000
Fax 93778 0
Email 93778 0
mathisg@unimelb.edu.au
Contact person for public queries
Name 93779 0
Dr Yee-Ming Melody Cheung
Address 93779 0
Austin Health,
145 Studley Rd, Heidelberg
Vic 3084
Country 93779 0
Australia
Phone 93779 0
+61 478690588
Fax 93779 0
Email 93779 0
melody.cheung@austin.org.au
Contact person for scientific queries
Name 93780 0
Dr Yee-Ming Melody Cheung
Address 93780 0
Austin Health,
145 Studley Rd, Heidelberg
Vic 3084
Country 93780 0
Australia
Phone 93780 0
+61 478690588
Fax 93780 0
Email 93780 0
melody.cheung@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 2372 0
Study protocol
Citation [1] 2372 0
Link [1] 2372 0
Email [1] 2372 0
Other [1] 2372 0
Type [2] 2373 0
Ethical approval
Citation [2] 2373 0
Link [2] 2373 0
Email [2] 2373 0
Other [2] 2373 0
Type [3] 2374 0
Ethical approval
Citation [3] 2374 0
Link [3] 2374 0
Email [3] 2374 0
Other [3] 2374 0
Type [4] 2446 0
Ethical approval
Citation [4] 2446 0
Link [4] 2446 0
Email [4] 2446 0
Other [4] 2446 0
Type [5] 2447 0
Ethical approval
Citation [5] 2447 0
Link [5] 2447 0
Email [5] 2447 0
Other [5] 2447 0
Summary results
No Results