Does removing both ovaries prior to menopause reduce breast cancer risk in BRCA1 and BRCA2 mutation carriers?
| ISRCTN | ISRCTN33767504 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN33767504 |
| Secondary identifying numbers | RGU/EX2202/20241031 |
- Submission date
- 08/09/2025
- Registration date
- 01/10/2025
- Last edited
- 29/09/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
It is unclear whether removing both ovaries and the fallopian tubes (bilateral salpingo-oophorectomy) before menopause reduces the risk of breast cancer in women who carry BRCA1 or BRCA2 gene mutations. There is no clear agreement in international guidelines either. Undertaking a randomised study is not practical because most women would not agree to be randomly assigned. Therefore, we propose an analysis of pooled individual data from established cohorts to better understand this.
The aims of this study are:
1. To estimate the effect of removing both ovaries and the fallopian tubes before menopause on breast cancer risk for (i) women with BRCA1 gene mutations and (ii) women with BRCA2 gene mutations.
2. To test whether any effect of ovary and fallopian tube removal is stronger when carried out at younger ages.
Who can participate?
Existing data will be included from cohort participants that meet the following criteria:
• carrier of pathogenic or likely pathogenic variant (class 4 or 5) in BRCA1 or BRCA2
• born after 1920
• aged at least 18 years at cohort entry
• no personal history of cancer (except cervix carcinoma in situ or non-melanoma skin cancer) at cohort entry
• no personal history of risk-reducing bilateral mastectomy at cohort entry
• follow-up information available (for at least invasive breast cancer, ductal carcinoma in situ and death)
What does the study involve?
This study will combine and analyse individual data from established cohorts to understand whether having both ovaries and the fallopian tubes removed before menopause lowers breast cancer risk for women with BRCA1 or BRCA2 mutation carriers. We will use an optimised analytical design to minimise bias and confounding.
Are There Any Benefits or Risks?
Since this study only looks at existing data, there are no direct benefits or risks to participants. However, results from this research may help influence future clinical care.
Where is the study run from?
Cancer Council Victoria, Australia
When is the study starting and how long is it expected to run for?
Data analysis will begin in Feb 2026 and take approximately 12 months to complete.
Who is funding the study?
The analyses will be conducted by researchers at Cancer Council Victoria, using local funds.
Who is the main contact?
Professor Roger Milne, Roger.Milne@cancervic.org.au
Contact information
Scientific, Principal Investigator
Level 8/200 Victoria Parade
East Melbourne
3002
Australia
 ORCID ID |
0000-0001-5764-7268 |
|---|---|
| Phone | +61 3 9514 6293 |
| Roger.Milne@cancervic.org.au |
Public
305 Grattan Street
Melbourne
3000
Australia
| Phone | +61 3 8559 8261 |
|---|---|
| Stephanie.nesci@petermac.org |
Study information
| Study design | Pooled analysis of multiple longitudinal observational cohort studies. |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Medical and other records |
| Study type | Prevention |
| Participant information sheet | Not applicable (retrospective study) |
| Scientific title | Pre-menopausal bilateral salpingo-oophorectomy and breast cancer risk for carriers of BRCA1 and BRCA2 pathogenic variants: A pooled cohort analysis |
| Study objectives | 1. Pre-menopausal risk reducing bilateral salpingo-oophorectomy is associated with reduced risk of breast cancer for BRCA2, but not BRCA1, pathogenic mutation carriers 2. Pre-menopausal risk reducing bilateral salpingo-oophorectomy before age 40 years is associated with greater reduced risk of breast cancer than pre-menopausal risk reducing bilateral salpingo-oophorectomy after age 40 years |
| Ethics approval(s) | Ethics approval not required |
| Health condition(s) or problem(s) studied | Breast cancer |
| Intervention | This is an observational study that involves analysing pooled individual data that has already been collected within established cohorts. No interventions or treatments will be given and no further data collected from study participants. |
| Intervention type | Other |
| Primary outcome measure | Diagnosis of invasive breast cancer or ductal carcinoma in situ (DCIS) derived from self-report (in follow-up questionnaires), pathology reports, medical records and linkages to cancer registries at any time during follow-up. |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 30/09/2021 |
| Completion date | 01/02/2027 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 5500 |
| Key inclusion criteria | 1. Carrier of pathogenic or likely pathogenic variant (class 4 or 5) in BRCA1 or BRCA2 2. Born after 1920 3. Aged at least 18 years at cohort entry 4. No personal history of cancer (except cervix carcinoma in situ or non-melanoma skin cancer) at cohort entry 5. No personal history of risk-reducing bilateral mastectomy at cohort entry |
| Key exclusion criteria | No follow-up information available |
| Date of first enrolment | 30/11/2025 |
| Date of final enrolment | 01/02/2026 |
Locations
Countries of recruitment
- Australia
- Austria
- Canada
- Czech Republic
- England
- France
- Germany
- Hungary
- Netherlands
- New Zealand
- Norway
- Poland
- Spain
- Sweden
- United Kingdom
- United States of America
Study participating centres
Philadelphia
19103
United States of America
New York
10027
United States of America
Fremont
94538
United States of America
Toronto
ON M5G 2C1
Canada
Philadelphia
19111
United States of America
Salt Lake City
84112
United States of America
Parkville
3010
Australia
Philadelphia
19104
United States of America
Barcelona
08035
Spain
Trinity Lane
Cambridge
CB2 1TN
United Kingdom
Marseille
13009
France
Amsterdam
1066 CX
Netherlands
Wien
1090
Austria
Oslo
0372
Norway
Greifswald
17475
Germany
Budapest
1122
Hungary
Lund
SE-221 00
Sweden
Szczecin
70-204
Poland
Brno
656 53
Czech Republic
Madrid
28029
Spain
Melbourne
3000
Australia
Auckland
1023
New Zealand
Sponsor information
Research organisation
Level 8/200 Victoria Parade
East Melbourne
3002
Australia
| Phone | +61 3 9514 6100 |
|---|---|
| enquiries@cancervic.org.au | |
| Website | https://www.cancervic.org.au |
"ROR" |
https://ror.org/023m51b03 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Location
- Australia
Results and Publications
| Intention to publish date | 01/05/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will not be made publicly available. Data may be available on reasonable request to the PIs of the component cohorts used in this study. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2 | 08/08/2025 | 29/09/2025 | No | No |
Additional files
Editorial Notes
08/09/2025: Trial's existence confirmed by Cancer Council.
