Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women with a BRCA1 or BRCA2 Mutation

Finch, Amy; Beiner, Mario; Lubiński, Jan; Lynch, Henry T.; Møller, Pål; Rosen, Barry P.; Murphy, Joan; Ghadirian, Parviz; Friedman, Eitan; Foulkes, William D.; Wagner, Teresa; Tung, Nadine; Couch, Fergus J.; Stoppa‐Lyonnet, Dominique; Ainsworth, Peter; Daly, Mary B.; Pasini, Babara; Gershoni‐Baruch, Ruth; Eng, Charis; Olopade, Olufunmilayo I.; Mclennan, June; Karlan, Beth Y.; Weitzel, Jeffrey N.; Sun, Ping; Narod, Steven A.

doi:10.1097/01.ogx.0000251480.69322.50

Cited by 52 publications

(86 citation statements)

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“…However, we also considered a lower estimate of 80% of PBSO effectiveness based on a large prospective cohort study. 21 Our use of higher effectiveness rates for PBSO likely contributes to the finding that not all women need undergo prophylactic surgery to realize benefits of a genetic screening program in Ashkenazi Jews, in contrast to the conclusion of Grann et al 45 that prophylactic surgery would need to be accepted by all participants to realize an overall benefit.…”

Section: Comparison With Previous Decision Analysescontrasting

confidence: 39%

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Cost-effectiveness of population-based BRCA1/2 testing and ovarian cancer prevention for Ashkenazi Jews: A call for dialogue

Rubinstein

Jiang

Dellefave

et al. 2009

Genetics in Medicine

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Purpose: About half of unaffected BRCA1/2 carriers have a negative family history, confounding efforts toward presymptomatic carrier identification. Ovarian cancer is preventable for known carriers but is otherwise highly lethal. Cost-effectiveness and gains in life expectancy are important factors in evaluating the desirability of population-based genetic screening, currently the only viable strategy to identify carriers with unrevealing family histories. Methods: Cost-utility analysis for a population-based genetic screening program offered to American Ashkenazi Jewish women aged 35-55 years measuring cancer incidence, life expectancy, and cost. Results: Our model predicts that a genetic screening program would result in 2811 fewer cases of ovarian cancer, with a life expectancy gain of 1.83 quality-adjusted life years among carriers. At a cost of $460 for founder mutation testing, the cost of the program is $8300 (discounted) per year of quality-adjusted life gained. Conclusion:In populations with a high prevalence of BRCA1/2 founder mutations, genetic screening may be cost-effective when compared with recommended public health interventions such as mammographic screening. We advocate the initiation of a dialogue among Jewish stakeholders, genetics professionals, and public health leaders to determine whether a population-based BRCA1/2 genetic screening program should be pursued. Genet Med 2009:11(9):629 -639. Key Words: BRCA1, BRCA2, decision analysis, ovarian carcinoma, population-based genetic screeningA n inherited predisposition to hereditary breast and ovarian cancer should be heralded by a strong cancer family history, but surprisingly often, it is not. Incomplete penetrance, sexlimited expression, limited family structure, and incomplete family history information all contribute to the frequent observation of hereditary cancer cases, which lack premonitory clues. Female BRCA1/2 carriers who are unaware of their genetic status cannot undertake recommended measures such as early mammography and breast magnetic resonance imaging (MRI) or avail themselves of risk-reducing salpingo-oophorectomy after completion of childbearing. Women with nonscreen detected, early-onset breast cancer and those who develop ovarian cancer can be expected to face much higher morbidity and mortality than if they were undergoing high-risk management.An underlying assumption in clinical cancer genetics is that by maximizing the efficiency of the referral pipeline through such means as physician and patient education and computerized family history tools, most unaffected BRCA1/2 carriers could be identified before developing cancer. High-risk management could then be instituted in a family-centered manner to reduce the cancer burden. Although this holds true for families with recognizable features of hereditary cancer, several studies suggest that about half of all BRCA1/2 families cannot be identified using this approach. [1][2][3][4][5][6][7][8] BRCA1/2 mutation prevalence rates have been measured in several population-based...

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Section: Comparison With Previous Decision Analysescontrasting

confidence: 39%

“…16 Struewing et al 19 Struewing et al 17 Hartge et al 18 2 Probability that a carrier will follow-up with PBSO: (P2) 0. 50 Rebbeck et al 20 Finch et al 21 Kauff et al 22 3 Amount of reduction due to PBSO in the probability that a carrier will get ovarian cancer: (P3) 0.96 Kauff et al 22 Rebbeck et al 25 4…”

Section: Life Expectancymentioning

confidence: 99%

Cost-effectiveness of population-based BRCA1/2 testing and ovarian cancer prevention for Ashkenazi Jews: A call for dialogue

Rubinstein

Jiang

Dellefave

et al. 2009

Genetics in Medicine

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“…For now, it is unlikely that annual gynaecological screening with TVU and CA125 will reduce mortality from ovarian cancer in BRCA1/2 mutation carriers. Prophylactic removal of the ovaries and fallopian tubes has proven its value as a risk-reducing strategy for ovarian cancer as well as breast cancer Rebbeck et al, 2002;Finch et al, 2006) and should therefore be the cornerstone in the management of BRCA1/2 mutation carriers, as long as no other effective screening tool is available. CI, confidence interval; SIR ¼ Standardized Incidence Rates.…”

Section: Discussionmentioning

confidence: 99%

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

et al. 2007

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BRCA1/2 mutation carriers are offered gynaecological screening with the intention to reduce mortality by detecting ovarian cancer at an early stage. We examined compliance and efficacy of gynaecological screening in BRCA1/2 mutation carriers. In this multicentre, observational, follow-up study we examined medical record data of a consecutive series of 888 BRCA1/2 mutation carriers who started annual screening with transvaginal ultrasonography and serum CA125 between 1993 and 2005. The women were annually screened for 75% of their total period of follow-up. Compliance decreased with longer follow-up. Five of the 10 incident cancers were interval tumours, diagnosed in women with a normal screening result within 3–10 months before diagnosis. No difference in stage distribution between incident screen-detected and interval tumours was found. Eight of the 10 incident cancers were stage III/IV (80%). Cancers diagnosed in unscreened family members had a similar stage distribution (77% in stage III/IV). The observed number of cases detected during screening was not significantly higher than expected (Standardized Incidence Ratio (SIR): 1.5, 95% confidence interval: 0.7–2.8). For the subgroup that was fully compliant to annual screening, a similar SIR was found (1.6, 95% confidence interval: 0.5–3.6). Despite annual gynaecological screening, a high proportion of ovarian cancers in BRCA1/2 carriers are interval cancers and the large majority of all cancers are diagnosed in advanced stages. Therefore, it is unlikely that annual screening will reduce mortality from ovarian cancer in BRCA1/2 mutation carriers.

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“…While ovarian screening in high-risk groups is not effective, breast cancer screening is indicated and there is evidence of increased sensitivity of magnetic resonance imaging (MRI) for detecting malignancies in younger BRCA carriers [8,9], compared to mammography. Risk-reducing mastectomy (RRM) and/or oophorectomy (RRSO) results in a significant decrease in mortality in high-risk women [6,7,10,11]. Domcheck et al [11] found that RRSO was associated with lower all-cause mortality, as well as lower breast cancerspecific and ovarian cancer-specific mortality.…”

Section: Introductionmentioning

confidence: 99%

“…Risk-reducing mastectomy (RRM) and/or oophorectomy (RRSO) results in a significant decrease in mortality in high-risk women [6,7,10,11]. Domcheck et al [11] found that RRSO was associated with lower all-cause mortality, as well as lower breast cancerspecific and ovarian cancer-specific mortality. Recent data suggest that a combination of RRM and RRSO at 40 years is the most effective way to improve survival in BRCA mutation carriers, and that performing RRM any earlier has little impact upon survival rates [13].…”

Section: Introductionmentioning

confidence: 99%

Looking different, feeling different: women’s reactions to risk-reducing breast and ovarian surgery

et al. 2011

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Objectives Most studies of quality of life following risk-reducing bilateral salpingo -oophorectomy (RRSO) and mastectomy (RRM) for inherited breast and ovarian cancer susceptibility were conducted before counseling protocols were established and included women at varying times since surgery. This study aimed to overcome these deficiencies and to provide current data on outcomes for this growing group of women.Methods Semi-structured interviews were used to explore the experiences of an Australian cohort of 40 high-risk women three years after they underwent RRM and/or RRSO. Data were analyzed using the method of constant comparison.Results Nineteen women underwent RRSO, 8 RRM and 13 both procedures. Two themes -looking different and feeling different -captured the psychosocial impact of surgery upon interviewees. All were relieved at having the risk of cancer substantially reduced that had previously been embodied in their breasts and ovaries; however, reducing risk by removing these body parts is not without costs. Interviewees reported experiencing a range of negative emotions and a range of unexpected bodily sensations following surgery and reflected upon both positive and negative changes in their appearance. Women said they had been unprepared for the lack of sensation in reconstructed breasts and/or the severity of menopausal symptoms, which often had a negative impact upon sexuality. ConclusionsAlthough women who undergo RR surgery are informed about its sequelae, however, few are entirely prepared for the reality of undergoing this procedure. We recommend that women who undergo these procedures should be provided with psychosocial support before and after RR surgery.

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Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women with a BRCA1 or BRCA2 Mutation

Cited by 52 publications

References 16 publications

Cost-effectiveness of population-based BRCA1/2 testing and ovarian cancer prevention for Ashkenazi Jews: A call for dialogue

Cost-effectiveness of population-based BRCA1/2 testing and ovarian cancer prevention for Ashkenazi Jews: A call for dialogue

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

Looking different, feeling different: women’s reactions to risk-reducing breast and ovarian surgery

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