Association of premenopausal risk-reducing salpingo-oophorectomy with breast cancer risk in BRCA1/2 mutation carriers: Maximising bias-reduction.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
06 2020
Historique:
received: 08 12 2019
revised: 28 02 2020
accepted: 09 03 2020
pubmed: 24 4 2020
medline: 11 11 2020
entrez: 24 4 2020
Statut: ppublish

Résumé

Whether risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers reduces the breast cancer (BC) risk is conflicting, potentially due to methodological issues of prior analysis. We analysed the association between premenopausal RRSO and BC risk in BRCA1/2 carriers after adjusting for potential biases. We analysed data from 444 BRCA1 and 409 BRCA2 carriers under age 51 with no cancer prior to genetic testing or during first 6 months of surveillance (to avoid cancer-induced testing bias and prevalent-cancer bias). Observation started 6 months after genetic testing (to avoid event-free time bias), until BC diagnosis, risk-reducing mastectomy (RRM) or death. A multistate model with four states (non-RRSO, RRSO, RRM and BC) and five transitions was fitted to characterise outcomes and to calculate the BC risk reduction after premenopausal RRSO (before age 51). A systematic review was performed to assess the association between premenopausal RRSO and BC. During a mean follow-up of 4.3 years, 96 women (11.3%) developed BC (54 BRCA1, 42 BRCA2). The risk of BC after premenopausal RRSO decreased significantly in BRCA1 carriers (hazard ratio (HR) = 0.45 [95% confidence interval (CI):0.22-0.92]), but was not conclusive in BRCA2 carriers (HR = 0.77 [95%CI:0.35-1.67]). The systematic review suggested that premenopausal RRSO is associated with a decrease of BC risk in both BRCA1 and BRCA2 carriers. Premenopausal RRSO was associated with BC risk reduction in BRCA1 carriers, which can help guide cancer risk-reducing strategies in this population. Longer follow-up and larger sample size may be needed to estimate the potential benefit in BRCA2 carriers.

Sections du résumé

BACKGROUND
Whether risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers reduces the breast cancer (BC) risk is conflicting, potentially due to methodological issues of prior analysis. We analysed the association between premenopausal RRSO and BC risk in BRCA1/2 carriers after adjusting for potential biases.
METHODS
We analysed data from 444 BRCA1 and 409 BRCA2 carriers under age 51 with no cancer prior to genetic testing or during first 6 months of surveillance (to avoid cancer-induced testing bias and prevalent-cancer bias). Observation started 6 months after genetic testing (to avoid event-free time bias), until BC diagnosis, risk-reducing mastectomy (RRM) or death. A multistate model with four states (non-RRSO, RRSO, RRM and BC) and five transitions was fitted to characterise outcomes and to calculate the BC risk reduction after premenopausal RRSO (before age 51). A systematic review was performed to assess the association between premenopausal RRSO and BC.
RESULTS
During a mean follow-up of 4.3 years, 96 women (11.3%) developed BC (54 BRCA1, 42 BRCA2). The risk of BC after premenopausal RRSO decreased significantly in BRCA1 carriers (hazard ratio (HR) = 0.45 [95% confidence interval (CI):0.22-0.92]), but was not conclusive in BRCA2 carriers (HR = 0.77 [95%CI:0.35-1.67]). The systematic review suggested that premenopausal RRSO is associated with a decrease of BC risk in both BRCA1 and BRCA2 carriers.
CONCLUSIONS
Premenopausal RRSO was associated with BC risk reduction in BRCA1 carriers, which can help guide cancer risk-reducing strategies in this population. Longer follow-up and larger sample size may be needed to estimate the potential benefit in BRCA2 carriers.

Identifiants

pubmed: 32325420
pii: S0959-8049(20)30150-7
doi: 10.1016/j.ejca.2020.03.009
pii:
doi:

Substances chimiques

BRCA1 Protein 0
BRCA1 protein, human 0
BRCA2 Protein 0
BRCA2 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

53-60

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare no conflicts of interest.

Auteurs

Neda Stjepanovic (N)

Vall d'Hebron University Hospital and Vall d'hebron Institute of Oncology (VHIO), Barcelona, Spain; Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address: neda.stjepanovic@sunnybrook.ca.

Guillermo Villacampa (G)

Vall d'Hebron University Hospital and Vall d'hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: gvillacampa@vhio.net.

Kevin T Nead (KT)

Basser Center for BRCA and Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA; Anderson Cancer Centre, Houston, TX, USA. Electronic address: ktnead@mdanderson.org.

Sara Torres-Esquius (S)

Vall d'Hebron University Hospital and Vall d'hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: storres@vhio.net.

Guadalupe G Melis (GG)

Universitat Politècnica de Catalunya, Barcelona, Spain. Electronic address: lupe.gomez@upc.edu.

Katherine L Nathanson (KL)

Basser Center for BRCA and Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA. Electronic address: knathans@upenn.edu.

Alexandre Teule (A)

Catalan Institute of Oncology, IDIBELL, Barcelona, Spain. Electronic address: ateule@iconcologia.net.

Joan Brunet (J)

Catalan Institute of Oncology, IDIBELL, Barcelona, Spain; Catalan Institute of Oncology, IDIBGI, Girona, Spain. Electronic address: jbrunet@iconcologia.net.

Teresa R Y Cajal (TR)

Hospital Sant Pau, Barcelona, Spain. Electronic address: tramon@santpau.cat.

Gemma Llort (G)

Hospital Universitari, Parc Taulí Sabadell, Consorci Sanitari de Terrassa, Barcelona, Spain. Electronic address: gllort@tauli.cat.

Rodrigo Dienstmann (R)

Vall d'Hebron University Hospital and Vall d'hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: rdienstmann@vhio.net.

Montserrat Rue (M)

University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain. Electronic address: montserrat.rue@udl.cat.

Susan M Domchek (SM)

Basser Center for BRCA and Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA. Electronic address: susan.domchek@uphs.upenn.edu.

Judith Balmaña (J)

Vall d'Hebron University Hospital and Vall d'hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: jbalmana@vhio.net.

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Classifications MeSH