Risk‐reducing salpingo‐oophorectomy and breast cancer incidence among Jewish BRCA1/BRCA2 ‐mutation carriers – an Israeli matched pair study

10548 Background: Uncertainty exists with regard to the role of bilateral salpingo-oophorectomy in altering the risk of breast cancer in BRCA-mutation carriers. Methods: Included were 1645 healthy Jewish Israeli BRCA1/2 -mutation carriers from a single center without prophylactic mastectomy. Carriers with and without risk-reducing bilateral salpingo-oophorectomy (RRBSO) were matched according to BRCA-mutation type (BRCA1 vs. BRCA2) and year of birth (±1 year). Hormonal and reproductive variables were compared and incidence of breast cancer recorded. Association between RRBSO and breast cancer was studied. Results: Seventy-seven and 50 matched-pairs had BRCA1 and BRCA2 mutation respectively. Fifty-two carriers had breast cancer, 21 in RRBSO-group and 31 in no- RRBSO group, with no statistically significant difference. When analysing each mutation group separately, stratified by age at surgery, no association between RRBSO and breast cancer incidence was found among BRCA1-mutation carriers. However, in BRCA2 mutation carriers, RRBSO was associated with a statistically significant decreased overall incidence of breast cancer, HR = 0.2 (confidence interval 0.44-0.913, p = 0.038). Breast cancer incidence was lower after 5, 10,15 and 20 years in BRCA2-mutation carriers with RRBSO compared to no-RRBSO. Age at menarche, age at surgery, parity and oral contraceptive use were not significant risk factors for breast cancer. Hormone replacement therapy was used by 62 mutation carriers, 52 in the RRBSO group and 10 in the no-RRBSO group, and its use did not alter breast cancer risk (p = 0.463). Conclusions: According to our findings, RRBSO is associated with a reduced risk of breast cancer only in BRCA2 mutation carriers, regardless of HRT use.

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Breast Cancer Incidence After Risk-Reducing Salpingo-Oophorectomy in BRCA1 and BRCA2 Mutation Carriers

Cancer Prevention Research ◽

10.1158/1940-6207.capr-12-0190 ◽

2012 ◽

Vol 5 (11) ◽

pp. 1291-1297 ◽

Cited By ~ 18

Author(s):

Ingrid E. Fakkert ◽

Marian J.E. Mourits ◽

Liesbeth Jansen ◽

Dorina M. van der Kolk ◽

Kees Meijer ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Incidence ◽

Brca2 Mutation ◽

Breast Cancer Incidence ◽

Brca1 And Brca2 ◽

Mutation Carriers ◽

Risk Reducing

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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Nature Communications ◽

10.1038/s41467-020-20496-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Juliette Coignard ◽

◽

Michael Lush ◽

Jonathan Beesley ◽

Tracy A. O’Mara ◽

...

Keyword(s):

Breast Cancer ◽

General Population ◽

Genome Wide Association Study ◽

Brca2 Mutation ◽

Risk Scores ◽

Genetic Modifiers ◽

Mutation Carriers ◽

Genotype Frequencies ◽

Genome Wide ◽

Brca1 Brca2

AbstractBreast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

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The frequency and outcome of breast cancer risk-reducing surgery in finnish BRCA1 and BRCA2 mutation carriers

Scandinavian Journal of Surgery ◽

10.1177/1457496913490460 ◽

2013 ◽

Vol 103 (1) ◽

pp. 34-40 ◽

Cited By ~ 5

Author(s):

L. Koskenvuo ◽

C. Svarvar ◽

S. Suominen ◽

K. Aittomäki ◽

T. Jahkola

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Brca2 Mutation ◽

Brca1 And Brca2 ◽

Mutation Carriers ◽

Risk Reducing

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Risk-Reducing Salpingo-Oophorectomy and Breast Cancer Risk Reduction in the Gynecologic Oncology Group Protocol-0199 (GOG-0199)

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz075 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Phuong L Mai ◽

Austin Miller ◽

Mitchell H Gail ◽

Steven Skates ◽

Karen Lu ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Incidence Rates ◽

Pathogenic Variant ◽

Risk Reducing ◽

Cancer Risk Reduction

Abstract Background Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2), a finding that has recently been questioned. Methods We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a BRCA1/2 pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group. Breast cancer hazard ratios (HRs) for time-dependent RRSO were estimated using Cox regression with age time-scale (4943 and 4990 women-years in RRSO and OCS cohorts, respectively). All statistical tests were two-sided. Results The RRSO cohort included 925 participants, and 1453 participants were in the OCS cohort (381 underwent RRSO during follow-up), with 88 incident breast cancers diagnosed. Among BRCA1/2 pathogenic variant carriers, a non-statistically significant lower breast cancer incidence was observed in the RRSO compared with the OCS cohort (HR = 0.86, 95% confidence interval = 0.45 to 1.67; P = .67). No difference was observed in the overall population or among subgroups stratified by prior breast cancer history or menopausal status. Seven fallopian tube and four ovarian cancers were prospectively diagnosed in the OCS cohort, and one primary peritoneal carcinoma occurred in the RRSO cohort. Conclusions These data suggest that RRSO might be associated with reduced breast cancer incidence among women with a BRCA1/2 pathogenic variant, although the effect, if present, is small. This evolving evidence warrants a thorough discussion regarding the impact of RRSO on breast cancer risk with women considering this intervention.

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Bilateral Risk-Reducing Oophorectomy in BRCA1 and BRCA2 Mutation Carriers

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2006.0017 ◽

2006 ◽

Vol 4 (2) ◽

pp. 177-182 ◽

Cited By ~ 19

Author(s):

Susan M. Domchek ◽

Jill E. Stopfer ◽

Timothy R. Rebbeck

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Reduction ◽

Hormone Replacement ◽

Brca2 Mutation ◽

Ovarian Cancer Risk ◽

Mutation Carriers ◽

Risk Reducing ◽

Cancer Risk Reduction

Bilateral risk-reducing oophorectomy (BRRO) is widely used for cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations. BRRO significantly reduces breast cancer risk by approximately 50% and ovarian cancer risk by 85% to 95%, but it may be accompanied by menopausal symptoms, impaired quality of life, and accelerated bone loss. Therefore, decisions regarding the timing of BRRO, the risks and benefits of a simultaneous hysterectomy, and the use of hormone replacement therapy (HRT) must be made in concert with the patient and individualized to their circumstances. However, recent data demonstrate that HRT after BRRO in unaffected premenopausal women does not negate the breast cancer risk reduction that BRRO provides. This article reviews the studies regarding BRRO in BRCA1/2 mutation carriers, with particular focus on the use of HRT.

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