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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

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

Prof Roger Milne
Scientific, Principal Investigator

Level 8/200 Victoria Parade
East Melbourne
3002
Australia

ORCiD logoORCID ID 0000-0001-5764-7268
Phone +61 3 9514 6293
Email Roger.Milne@cancervic.org.au
Mrs Stephanie Nesci
Public

305 Grattan Street
Melbourne
3000
Australia

Phone +61 3 8559 8261
Email Stephanie.nesci@petermac.org

Study information

Study designPooled analysis of multiple longitudinal observational cohort studies.
Primary study designObservational
Secondary study designCohort study
Study setting(s)Medical and other records
Study typePrevention
Participant information sheet Not applicable (retrospective study)
Scientific titlePre-menopausal bilateral salpingo-oophorectomy and breast cancer risk for carriers of BRCA1 and BRCA2 pathogenic variants: A pooled cohort analysis
Study objectives1. 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) studiedBreast cancer
InterventionThis 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 typeOther
Primary outcome measureDiagnosis 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 measuresThere are no secondary outcome measures
Overall study start date30/09/2021
Completion date01/02/2027

Eligibility

Participant type(s)Other
Age groupAdult
Lower age limit18 Years
SexFemale
Target number of participants5500
Key inclusion criteria1. 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 criteriaNo follow-up information available
Date of first enrolment30/11/2025
Date of final enrolment01/02/2026

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

NRG Oncology
Four Penn Center, 1600 JFK Blvd, Suite 1020
Philadelphia
19103
United States of America
Columbia University
116th and Broadway
New York
10027
United States of America
Cancer Prevention Institute of California
2201 Walnut Ave
Fremont
94538
United States of America
Cancer Care Ontario
620 University Ave
Toronto
ON M5G 2C1
Canada
Fox Chase Cancer Centre
333 Cottman Ave
Philadelphia
19111
United States of America
The University of Utah Health Sciences Centre
201 Presidents' Cir
Salt Lake City
84112
United States of America
The University of Melbourne
Grattan Street
Parkville
3010
Australia
University of Pennsylvania
3451 Walnut Street
Philadelphia
19104
United States of America
Vall d'Hebron University Hospital
Pg. de la Vall d'Hebron, 119, Horta-Guinardó
Barcelona
08035
Spain
University of Cambridge
The Old School
Trinity Lane
Cambridge
CB2 1TN
United Kingdom
Institute Paoli-Calmettes
232 Bd de Sainte-Marguerite
Marseille
13009
France
The Netherlands Cancer Institute
Plesmanlaan 121
Amsterdam
1066 CX
Netherlands
Medical University of Vienna
Spitalgasse 23
Wien
1090
Austria
Oslo University Hospital
Sognsvannsveien 20
Oslo
0372
Norway
University Medicine of Greifswald
Fleischmannstraße 8
Greifswald
17475
Germany
National Institute of Oncology
Ráth György u. 7-9
Budapest
1122
Hungary
Lund University
Box 188
Lund
SE-221 00
Sweden
The International Hereditary Cancer Center
ul. Rybacka 1
Szczecin
70-204
Poland
Masaryk Memorial Cancer Institute
Žlutý kopec 7
Brno
656 53
Czech Republic
Spanish National Cancer Research
C. de Melchor Fernández Almagro, 3, Fuencarral-El Pardo
Madrid
28029
Spain
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne
3000
Australia
Auckland Hospital
2 Park Road
Auckland
1023
New Zealand

Sponsor information

Funders

Funder type

Charity

Cancer Council Victoria
Private sector organisation / Other non-profit organizations
Location
Australia

Results and Publications

Intention to publish date01/05/2027
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal
IPD sharing planThe 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

47960 Protocol 08Aug2025_V2.pdf

Editorial Notes

08/09/2025: Trial's existence confirmed by Cancer Council.