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

Stjepanovic, Neda; Villacampa, Guillermo; Nead, Kevin T.; Torres-Esquius, Sara; Melis, Guadalupe Gómez; Nathanson, Katherine L.; Teulé, Alexandre; Brunet, Joan; Cajal, Teresa Ramón y; Llort, Gemma; Dienstmann, Rodrigo; Rué, Montserrat; Domchek, Susan M.; Balmañà, Judith

doi:10.1016/j.ejca.2020.03.009

Cited by 19 publications

(22 citation statements)

References 20 publications

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“…A 2020 study including 853 premenopausal carriers of a pathogenic BRCA1/2 variant showed that premenopausal RRSO decreased breast cancer risk in BRCA1 pathogenic variant carriers (HR, 0.45; 95% CI, 0.22-0.92), but not in BRCA2 pathogenic variant carriers (HR, 0.77; 95% CI, 0.35-1.67). 192 Analysis for this study began observation 6 months after genetic testing to avoid event-free time bias.…”

Section: Bilateral Salpingo-oophorectomymentioning

confidence: 99%

Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Daly

Pal

Berry

et al. 2021

Journal of the National Comprehensive Cancer Network

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597

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The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

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Section: Bilateral Salpingo-oophorectomymentioning

confidence: 99%

Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Daly

Pal

Berry

et al. 2021

Journal of the National Comprehensive Cancer Network

Self Cite

677

597

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“…Evidence for an association between rrBSO and breast cancer risk is based on observational studies (3,(4)(5)(6)(7)(8)(9)(10)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43), which contain inherent biases that must be considered when interpreting their results and applying them to clinical practice. These biases have been discussed since 2003 (see Table 2; refs.…”

Section: Types Of Bias In Observational Studies Of Rrbso and Breast Cancer Riskmentioning

confidence: 99%

“…Risk-reducing bilateral salpingo-oophorectomy (rrBSO) is highly effective at reducing the risk of tuboovarian cancer (2)(3). In contrast, the role of rrBSO in mitigating breast cancer risk in mutation carriers, while previously widely accepted and incorporated in clinical guidelines (see Table 1), is now less clear and challenged by emerging contradictory evidence (4)(5)(6)(7)(8)(9)(10). This article reviews the literature on rrBSO and subsequent risk of first breast cancer for mutation carriers and suggests modifications to existing guidelines based on compilation of new evidence from recent studies.…”

Section: Introductionmentioning

confidence: 99%

Bilateral Salpingo-oophorectomy and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Assessing the Evidence

Conduit

Milne

Friedlander

et al. 2021

Cancer Prevention Research

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Without preventive interventions, women with germline pathogenic variants in BRCA1 or BRCA2 have high lifetime risks for breast cancer and tubo-ovarian cancer. The increased risk for breast cancer starts at a considerably younger age than that for tubo-ovarian cancer. Riskreducing bilateral salpingo-oophorectomy (rrBSO) is effective in reducing tubo-ovarian cancer risk for BRCA1 and BRCA2 mutation carriers, but whether it reduces breast cancer risk is less clear. All studies of rrBSO and breast cancer risk are observational in nature and subject to various forms of bias and confounding, thus limiting conclusions that can be drawn about causation. Early studies supported a statistically significant protective association for rrBSO on breast cancer risk, which is reflected by several international guidelines that recommend consideration of premenopausal rrBSO for breast cancer risk reduction. However, these historical studies were hampered by the presence of several important biases, including immortal person-time bias, confounding by indication, informative censoring, and confounding by other risk factors, which may have led to overestimation of any protective benefit. Contemporary studies, specifically designed to reduce some of these biases, have yielded contradictory results. Taken together, there is no clear and consistent evidence for a role of premenopausal rrBSO in reducing breast cancer risk in BRCA1 or BRCA2 mutation carriers.

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“…Die durchschnittliche Operationszeit für eine RRSO ohne peritoneale Biopsie betrug 64,3 Minuten verglichen mit 77,8 Minuten für eine RSSO mit peritonealer Biopsie. Das kam einer statistisch signifikanten Verlängerung der Operationszeit von 16 % gleich (13,5 Minuten, p = 0,0383).…”

Section: Objectiveunclassified

“…Due to ineffective screening programs for OC, risk reducing bilateral salpingo-oophorectomy (RRSO) is suggested for gBRCA1/2 -mutation carriers 3 .The goal is to undergo RRSO as late as possible to reduce side effects caused by iatrogenic menopause and premature ovarian failure (POF) but early enough to prevent OC. At the moment, according to international guidelines RRSO is recommended between the age of 35 and 40 for gBRCA1 mutation carriers and between the age of 40 and 45 for gBRCA2 mutation carriers but at least 5 years before the first diagnosis of OC in the family occurred 3 , 5 . These recommendations are based on individual risk calculation with the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a validated calculation program for cancer risks 6 , 7 .…”

Section: Objectivementioning

confidence: 99%

Role of Routine Peritoneal Biopsies During Risk Reducing Salpingo-Oophorectomy (RRSO)

Pross

Karsten

Blohmer

et al. 2021

Geburtshilfe Frauenheilkd

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Objective The objective of this retrospective study was to assess the role of routine peritoneal biopsies during risk reducing salpingo-oophorectomy (RRSO). Methods Data of 204 women who underwent RRSO between January 1, 2014 and February 20, 2020 at Charité – Universitätsmedizin Berlin, Campus Mitte were retrospectively analyzed. RRSO was done according to the standard operating procedures of the German Consortium Hereditary Breast and Ovarian Cancer (GC-HBOC) with peritoneal washing and several peritoneal biopsies. Specimen collected during RRSO were analyzed using the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Perioperative complications were classified using the Clavien-Dindo-Classification. Results 147 women who underwent RRSO had peritoneal biopsies and pelvic washing, 44 women had none of that. 123 patients (64.4%) carried a pathologic variant in gBRCA1, 53 (27.7%) carried a pathologic variant in gBRCA2. Histopathological evaluation identified four patients (2.1%) with pathological findings. Neither peritoneal biopsies nor pelvic washings revealed additional information after histological examination. There was no statistically significant difference in complication rate between the two groups. The mean surgery time for RRSO without peritoneal biopsies was 64.3 minutes compared to 77.8 minutes with peritoneal biopsies. That shows a statistically significant prolongation of 16% (13.5 minutes, p = 0.0383). Conclusions The routine use of peritoneal biopsies during RRSO does not improve detection of occult ovarian cancer or STIC but prolongs the operation time significantly. By omitting peritoneal biopsies in RRSO not only perioperative risks are diminished but also costs could be reduced by shortening of surgery time as well as decreased number of pathological samples.

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

Cited by 19 publications

References 20 publications

Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Bilateral Salpingo-oophorectomy and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Assessing the Evidence

Role of Routine Peritoneal Biopsies During Risk Reducing Salpingo-Oophorectomy (RRSO)

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