Original Research
Prophylactic Salpingectomy and Delayed
Oophorectomy as an Alternative for BRCA
Mutation Carriers
Janice S. Kwon, MD, Anna Tinker, MD, Gary Pansegrau, MD, Jessica McAlpine, MD, Melissa Housty, MSN,
Mary McCullum, MSN, and C. Blake Gilks, MD
OBJECTIVE: Prophylactic bilateral salpingo-oophorectomy
is advised for women with BRCA mutations, but there
are adverse consequences of premature menopause. The
majority of BRCA-associated ovarian cancers appear to
arise in the fallopian tube; therefore, salpingectomy may
be an alternative to bilateral salpingo-oophorectomy. We
compared the costs and benefits of salpingectomy with
bilateral salpingo-oophorectomy among BRCA mutation
carriers.
METHODS: We developed a Markov Monte Carlo sim-
ulation model to compare three strategies for risk
reduction in women with BRCA mutations: 1) bilateral
salpingo-oophorectomy; 2) bilateral salpingectomy; and
3) bilateral salpingectomy with delayed oophorectomy.
Net health benefits were measured in years-of-life expec-
tancy and quality-adjusted life-year expectancy, and the
primary outcome was the incremental cost-effectiveness
ratio. The model estimated the number of future breast
and ovarian cancers and cardiovascular deaths attributed
to premature menopause with each strategy.
RESULTS: Bilateral salpingo-oophorectomy was associated
with the lowest cost and highest life expectancy compared
with the other two strategies. When quality-of-life meas-
ures were included, salpingectomy followed by delayed
oophorectomy yielded the highest quality-adjusted life
See related editorial on page 4.
From the University of British Columbia and BC Cancer Agency, Vancouver,
British Columbia, Canada.
Supported by an OvCaRe internal grant.
Corresponding author: Janice S. Kwon, MD, Division of Gynecologic Oncology,
University of British Columbia, 2775 Laurel Street, 6th Floor, Vancouver, BC,
Canada, V5Z 1M9; e-mail: janice.kwon@vch.ca.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2012 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/13
14 VOL. 121, NO. 1, JANUARY 2013
expectancy with incremental cost-effectiveness ratios of
$37,805 and $89,680 per quality-adjusted life-year for
BRCA1 and BRCA2, respectively, relative to salpingectomy
alone. Bilateral salpingo-oophorectomy yielded the lowest
number of future breast and ovarian cancers compared
with the other two strategies.
CONCLUSION: Bilateral salpingo-oophorectomy offers
the greatest risk reduction for breast and ovarian cancer
among BRCA mutation carriers. However, when consid-
ering quality-adjusted life expectancy, bilateral salpin-
gectomy with delayed oophorectomy is a cost-effective
strategy and may be an acceptable alternative for those
unwilling to undergo bilateral salpingo-oophorectomy.
(Obstet Gynecol 2013;121:14–24)
DOI: http://10.1097/AOG.0b013e3182783c2f
C
urrent recommendations for young women who
are carriers of a BRCA germline mutation include
bilateral salpingo-oophorectomy by the age of 40 years
or on completion of childbearing to reduce their risk of
ovarian cancer.1,2 This intervention has been proven to
decrease the risk of ovarian cancer by approximately
80–90%, risk of breast cancer by 50%,3 and cancer-
related mortality by approximately 60%.4 Despite this
widespread recommendation, many of these women
are reluctant to have prophylactic or risk-reducing
bilateral salpingo-oophorectomy at an early age,
because of the consequences relating to estrogen defi-
ciency, including vasomotor symptomatology, urogen-
ital atrophy, risk of osteoporosis, and cardiovascular
disease. In fact, among BRCA mutation carriers, the
proportion undergoing prophylactic bilateral salpingo-
oophorectomy is estimated to be only 60–70%.5–7
It has long been recognized that the vast majority
of ovarian cancers diagnosed in BRCA mutation carriers
are high-grade serous carcinomas.8 However, there is
increasing evidence that these cancers do not exclu-
sively arise in the ovary. A high proportion of these
OBSTETRICS & GYNECOLOGY
carcinomas identified incidentally at prophylactic bilat-
eral salpingo-oophorectomy are invasive high-grade
serous carcinomas of the fallopian tube or serous tubal
intraepithelial carcinomas.9–20 This observation chal-
lenges the existing recommendation for prophylactic
bilateral salpingo-oophorectomy, and it raises the pos-
sibility that prophylactic bilateral salpingectomy may
be sufficient to reduce the risk of fallopian tube carci-
noma while obviating the need for oophorectomy and
its inherent consequences of estrogen deficiency. Pro-
phylactic salpingectomy would not be expected
to reduce breast cancer risk in this population, but it
may reduce risk of premature death secondary to
cardiovascular disease in women who have been ren-
dered menopausal as a result of prophylactic bilateral
salpingo-oophorectomy. It is unlikely that a randomized
trial will ever be feasible to compare prophylactic bilat-
eral salpingo-oophorectomy with prophylactic salpin-
gectomy in this high-risk population. However,
decision-analytic modeling can compare the costs, risks,
and benefits of prophylactic salpingectomy with pro-
phylactic bilateral salpingo-oophorectomy in a hypo-
thetical cohort of women with BRCA germline
mutations. Our objective was to compare the costs
and benefits of salpingectomy with bilateral salpingo-
oophorectomy among BRCA mutation carriers.
MATERIALS AND METHODS
This study was approved by the research ethics board of
the University of British Columbia and the British
Columbia Cancer Agency. We developed a Markov
Monte Carlo simulation model to estimate the costs and
benefits of three risk-reducing strategies in BRCA muta-
tion carriers who have not yet had breast or ovarian
cancer: 1) bilateral salpingo-oophorectomy at age 40
years (reference strategy, as per the American College
of Obstetricians and Gynecologists)2; 2) bilateral salpin-
gectomy at age 40 years; and 3) bilateral salpingectomy
at age 40 years followed by bilateral oophorectomy at
age 50 years. The benefit for each strategy was calcu-
lated in years of life gained as well as quality-adjusted
years of life gained relative to an alternate strategy.
Average lifetime costs were estimated in Canadian dol-
lars in the year 2012. All direct and indirect costs were
estimated for services rendered through the British
Columbia Medical Services Plan21 and surgical treat-
ment and outpatient chemotherapy costs through the
Canadian Institute for Health Information22 and the
British Columbia Cancer Agency. Opportunity costs
were estimated from employment time lost based on
average hourly wages from Statistics Canada.23 The
primary outcome measure was the incremental cost-
effectiveness ratio defined as the additional cost divided
VOL. 121, NO. 1, JANUARY 2013
by the incremental health benefit compared with an
alternate strategy. A strategy was strongly dominated if
it was more costly and less effective than an alternate
strategy. A strategy was considered cost-effective if
its incremental cost-effectiveness ratio was between
$50,000 and $100,000 per year of life gained.24 As per
the U.S. Panel on Cost-effectiveness in Health and Med-
icine, we adopted a societal perspective and discounted
all costs and benefits at a rate of 3% per year.25
Women with BRCA 1 or BRCA2 mutations com-
prise a hypothetical cohort residing in one of five
Markov health states: 1) well; 2) at risk for breast and
ovarian cancer; 3) breast cancer; 4) ovarian cancer; and
5) dead. They enter the model at age 30 years in the
health state “at risk for breast cancer and ovarian
cancer.” In the base case for this model, all women
undergo the assigned risk-reducing intervention.
Women diagnosed with breast or ovarian cancer transi-
tion to the “breast cancer” or “ovarian cancer” state,
respectively, and in this state, they are subject to
cancer-related mortality risks as well as age-dependent
competing mortality risks according to Canadian life
tables.26 We assumed that BRCA-associated ovarian can-
cer could arise in either the fallopian tube or ovary and
that the presentation, treatment, and outcomes were
comparable regardless of site of origin. Women with
breast cancer remain at risk for recurrent or new breast
cancer for up to 25 years if they have undergone breast-
conserving surgery,27–31 but if they undergo bilateral
mastectomy, this risk is reduced by 95%. If they have
survived ovarian cancer for longer than 10 years, they
transition to the “well” state because their mortality risks
are estimated to be comparable with age-matched
women without cancer. This process continues in yearly
cycles until all women in the cohort reach the “dead”
state because of cancer or other causes.
Because the cancer phenotype is different for
BRCA1 and BRCA2 mutation carriers (ovarian cancer
risk is higher and average age at diagnosis is lower in
BRCA1 compared with BRCA2, and “triple-negative”
breast cancers are more likely in BRCA1 than
BRCA2),4,32,33 we calculated separate incremental cost-
effectiveness ratios for each gene. We assumed that ovar-
ian cancer risk reduction from prophylactic bilateral sal-
pingo-oophorectomy at age 40 years was 80% in both
BRCA1 and BRCA2 mutation carriers3,34,35 and 60% with
prophylactic salpingectomy based on the assumption
that the fallopian tube represents the primary site in
60% of BRCA-associated ovarian cancers.9–11,13,15,17,18,36
We assumed a 40% and 70% reduction in breast cancer
risk from prophylactic bilateral salpingo-oophorectomy
at age 40 years in BRCA1 and BRCA2 mutation carriers,
respectively,3,4 but with an increased risk of premature
Kwon et al Salpingectomy and BRCA Mutation Carriers 15
death from cardiovascular disease according to outcomes
from the Nurses’ Health Study.37 We assumed that sal-
pingectomy did not reduce breast cancer risk.38
We assumed that quality of life in women undergo-
ing prophylactic bilateral salpingo-oophorectomy at age
40 years would be compromised compared with those
undergoing prophylactic salpingectomy alone. Quality-
adjusted life-years were calculated by applying utilities to
health states, which represent patient preferences for
a year of life under specific conditions, for example,
a year of life at age 40 years after having prophylactic
bilateral salpingo-oophorectomy or a year of life after
being diagnosed with ovarian cancer. Although pro-
phylactic bilateral salpingo-oophorectomy at age 40
years has a utility of 0.82,39 there is no available literature
on utilities for salpingectomy. Assuming a postoperative
complication rate of 1.5–5%,40,41 and that ovarian func-
tion remains largely unaffected after salpingectomy,42–44
we arbitrarily assigned a utility of 0.99 for this procedure.
We estimated that 30% of women would choose to
undergo prophylactic mastectomy, ranging from 21%
between the ages of 25 and 60 years45 to 34% between
the ages of 23 and 64 years in our population based on
data provided by the British Columbia Cancer Agency
Hereditary Cancer Program high-risk clinic, which in-
cludes approximately 450 women with confirmed BRCA
mutations.46 We assumed that these women were eligible
for reconstruction with a transverse rectus abdominis
myocutaneous flap with a utility of 0.87.47
We assumed that 50% of women diagnosed with
breast cancer would choose bilateral mastectomy, and
the other half would choose breast-conserving surgery
(lumpectomy with sentinel node biopsy).48–51 Accord-
ingly, those who had breast-conserving surgery
received adjuvant radiotherapy. We assumed that these
women would receive adjuvant chemotherapy as per
British Columbia Cancer Agency protocol for high-risk
young women comprised of four cycles of doxorubicin
and cyclophosphamide followed by 12 weekly cycles
of paclitaxel.52 We assumed that all women diagnosed
with ovarian cancer would undergo laparotomy, hys-
terectomy, bilateral salpingo-oophorectomy, and stag-
ing or tumor debulking. We estimated that they would
receive adjuvant chemotherapy comprised of six cycles
of intravenous carboplatin and paclitaxel (and intra-
peritoneal chemotherapy for optimally debulked
advanced-stage disease).53
We conducted a Monte Carlo simulation to
estimate the number of subsequent breast and ovarian
cancer cases expected with each strategy as well as the
number of excess cardiovascular deaths attributed
to premature menopause from bilateral salpingo-
oophorectomy. Extensive sensitivity analyses were
16 Kwon et al Salpingectomy and BRCA Mutation Carriers
done to account for uncertainty around various
parameters, including costs of treatment (to approxi-
mate costs in the United States), the proportion of
BRCA-associated ovarian cancers arising in the fallo-
pian tube and extent of risk reduction from prophy-
lactic salpingectomy, and the ages and utilities
associated with the different surgical strategies.
Selected data for the base case of our model are pro-
vided in Table 1. The model was programmed using
TreeAge Pro 2011.
RESULTS
The average discounted costs, life expectancy, quality-
adjusted life expectancy, and incremental cost-
effectiveness ratios for women with BRCA1 and BRCA2
mutations are provided in Table 2. Bilateral salpingo-
oophorectomy at age 40 years was the dominant strat-
egy for both BRCA1 and BRCA2 carriers, because it
was least costly and most effective in terms of overall
life expectancy. Prophylactic salpingectomy at age 40
years followed by delayed oophorectomy at age 50
years had the highest quality-adjusted life expectancy
with favorable incremental cost-effectiveness ratios of
$37,805 and $89,680 per quality-adjusted life-year
gained for BRCA1 and BRCA2 mutation carriers,
respectively, relative to salpingectomy alone.
Our results were stable over a wide range of costs,
including estimates for breast and ovarian cancer
treatment that would be relevant in the U.S. health
care system. Our results were also stable over a plau-
sible range of utilities representing quality of life.
Figure 1 illustrates a sensitivity analysis on the utility
of prophylactic bilateral salpingo-oophorectomy at age
40 years. The utility of prophylactic bilateral salpingo-
oophorectomy had to exceed 0.93 for this intervention
to yield a higher quality-adjusted life expectancy than
prophylactic salpingectomy followed by delayed
oophorectomy. In our base case, prophylactic bilateral
salpingo-oophorectomy had a utility of 0.82, implying
that a year of life after prophylactic bilateral salpingo-
oophorectomy is considered equivalent to 0.82 of
a year in perfect health without prophylactic bilateral
salpingo-oophorectomy.
Our results were sensitive to variations in the age
at prophylactic surgery. Figure 2 illustrates a two-way
sensitivity analysis on the ages at salpingectomy and
delayed oophorectomy to estimate whether earlier
age thresholds for these procedures would be compa-
rable to bilateral salpingo-oophorectomy at age
40 years with respect to life expectancy as the net
health benefit. The sensitivity analysis demonstrates
that when women have salpingectomy at 35 years
of age followed by oophorectomy by the age of
OBSTETRICS & GYNECOLOGY
Table 1. Selected Data for Base Case
Probabilities Estimate Range

BRCA1 lifetime risks66

Ovarian cancer 40 35–46
Breast cancer 57 44–66
BRCA2 lifetime risks66
Ovarian cancer 18 13–23
Breast cancer 49 40–57
Bilateral salpingo-oophorectomy at age 40 y
Ovarian cancer risk reduction3,35 80 79–90
Breast cancer risk reduction—BRCA1/23,35 40/70 30–50/50–80
Excess mortality from cardiovascular disease37 0.0077 0.005–0.01
Salpingectomy at age 40 y
Ovarian cancer risk reduction9–13,15,17–19 60 18–90
Breast cancer risk reduction 0
Prophylactic mastectomy
Breast cancer risk reduction4,72–75 95 85–100
Recurrent or new breast cancer risk,
without prophylactic mastectomy
10-y ipsilateral breast cancer28,31 8 6–10
10-y contralateral breast cancer27–31 22 16–30
25-y contralateral breast cancer28 47 38–56
10-y mortality27,76–78 30 20–40
Breast cancer treatment
Proportion choosing bilateral 50 27–100
mastectomy48–51
Ovarian cancer outcome
10-y mortality79–81 50 40–60
Utilities for health states
Well82 0.79–1.0 0.79–1.0
Prophylactic bilateral salpingo-oophorectomy 0.82 0.76–0.88
at age 40 y83–86
Prophylactic mastectomy83–85 0.86 0.82–0.91
Prophylactic bilateral salpingo-oophorectomy 0.79 0.73–0.86
at age 40 y and mastectomy83–86
Prophylactic mastectomy with transverse rectus 0.87 0.70–0.90
abdominis myocutaneous flap47
Prophylactic salpingectomy 0.99 0.90–1.0
Ovarian cancer83,84,87 0.65 0.45–0.86
Breast cancer83,84,87–89 0.77 0.50–0.85
Health service or procedure
Consultation21
Initial $135 $100–300
Follow-up $46 $30–60
Surgeon or pathologist fees21
Complete mastectomy $465 $400–1,000
Partial mastectomy with sentinel node biopsy $698 $500–1,000
Breast reconstruction with transverse rectus abdominis $1,002 $900–2,000
myocutaneous flap
Laparoscopic bilateral salpingo-oophorectomy at $258 $200–1,500
age 40 y or salpingectomy
Ovarian cancer debulking $770 $700–3,000
Pathologist examination $135 $100–200
Hospital and treatment costs for surgery22,90
Breast cancer surgery $3,911 $3,000–20,000
Ovarian cancer surgery $10,797 $7,000–40,000
Prophylactic mastectomy with reconstruction and bilateral $7,795 $7,000–25,000
salpingo-oophorectomy at age 40 y
Prophylactic bilateral salpingo-oophorectomy at age $3,173 $3,000–10,000
40 y or salpingectomy
(continued )

VOL. 121, NO. 1, JANUARY 2013 Kwon et al Salpingectomy and BRCA Mutation Carriers 17
Table 1. Selected Data for Base Case (continued )
Probabilities Estimate Range

Costs of adjuvant therapy53,91

Adjuvant chemotherapy for ovarian cancer $7,596 $7,000–20,000
Adjuvant chemotherapy for high-risk breast cancer $10,128 $9,000–30,000
Adjuvant radiotherapy for breast cancer91 $11,711 $10,000–50,000
Opportunity costs23
Patient costs after cancer treatment (average 30 wk) $25,800 $20,000–30,000
Patient costs after prophylactic surgery (average 6 wk) $4,920 $3,000–7,000
Data are % unless otherwise specified.
Ovarian cancer includes fallopian tube and ovary as the primary site.
All costs are expressed in Canadian dollars.

46 years, costs and life expectancy are favorable com-
pared with bilateral salpingo-oophorectomy at age 40
years given a willingness-to-pay threshold of $100,000
per year of life gained. Prophylactic salpingectomy at
age 36 years followed by oophorectomy at age
42 years yields favorable costs and life expectancy
compared with bilateral salpingo-oophorectomy at
age 40 years.
Our results were also sensitive to varying estimates
of the proportion of BRCA-associated ovarian cancers
arising in the fallopian tube and the relative risk of these
cancers after prophylactic salpingectomy. Assuming

Table 2. Average Discounted Costs, Life Expectancy, and Incremental Cost-Effectiveness Ratios for Base
Case
Incremental
Cost-
Effectiveness
Average Incremental Cost- Average Quality- Ratios (Δ Cost per
Discounted Average Life Effectiveness Ratio Adjusted Quality-Adjusted
Costs Expectancy (Δ Cost per Year of Life-Year Life-Year Gained)
Testing Strategy (Canadian $) Gain (y) Life Gained) Expectancy Gain (Canadian $)

BRCA1
Bilateral salpingo- $25,987 21.154 — 17.557 —
oophorectomy
at age 40 y
Prophylactic (bilateral) $38,208 20.739 Dominated 18.167 $20,050
salpingectomy
at age 40 y
Prophylactic $41,577 20.830 Dominated 18.256 $37,805
salpingectomy
at age 40 y,
prophylactic
oophorectomy
at age 50 y
BRCA2
Bilateral salpingo- $16,932 22.618 — 18.873 —
oophorectomy
at age 40 y
Prophylactic $33,150 22.081 Dominated 19.505 $25,658
(bilateral)
salpingectomy
at age 40 y
Prophylactic $37,686 22.135 Dominated 19.555 $89,680
salpingectomy
at age 40 y,
prophylactic
oophorectomy
at age 50 y
Dominated, strategy is more costly and less effective than the preceding strategy.

18 Kwon et al Salpingectomy and BRCA Mutation Carriers OBSTETRICS & GYNECOLOGY

 Prophylactic salpingectomy
Prophylactic salpingectomy with
delayed oophorectomy
BSO
Threshold Values:
Utility of prophylactic BSO=0.93
Expected value=18.26
19.0
(quality-adjusted life years)
18.5
18.0
Effectiveness
17.5
17.0
16.5
16.0
15.5
0.5 0.6 0.7 0.8 0.9 1.0
Utility of prophylactic BSO
Fig. 1. Sensitivity analysis on the utility of prophylactic
bilateral salpingo-oophorectomy (BSO) at age 40 years. As
the utility of BSO increases, so does the quality-adjusted
life expectancy of bilateral salpingo-oophorectomy BSO.
The utility of BSO must exceed 0.93 for this strategy to yield
a higher quality-adjusted life expectancy (at expected value
of 18.26 quality-adjusted life years) than prophylactic sal-
pingectomy or prophylactic salpingectomy with delayed
oophorectomy.
Kwon. Salpingectomy and BRCA Mutation Carriers. Obstet
Gynecol 2013.
a higher proportion of these cancers arising in the fallo-
pian tube, there is a higher magnitude of risk reduction
from salpingectomy. Figure 3 illustrates that as the mag-
nitude of risk reduction increases (and relative risk
of ovarian cancer after salpingectomy decreases), the
smaller the benefit of additional oophorectomy in terms
of net health benefit, which increases the incremental
cost-effectiveness ratio. Conversely, the lower the pro-
portion of BRCA-associated ovarian cancers arising in
the fallopian tube, the lower the risk reduction after
salpingectomy. This translates into a greater benefit of
additional oophorectomy compared with salpingectomy
alone, which subsequently reduces the incremental cost-
effectiveness ratio. In our base case, prophylactic salpin-
gectomy and bilateral salpingo-oophorectomy reduced
BRCA-associated ovarian cancer risks by 60% and 80%,
VOL. 121, NO. 1, JANUARY 2013
Prophylactic salpingectomy with
delayed oophorectomy
BSO
50
prophylactic oophorectomy
48
Age at delayed
46
44
42
40
30 32 34 36 38 40
Age at prophylactic salpingectomy
Fig. 2. Two-way sensitivity analysis on the ages at pro-
phylactic salpingectomy and delayed oophorectomy. The
earlier prophylactic salpingectomy is done, the longer
oophorectomy can be delayed for the net health benefit
(overall life expectancy) to be comparable to that of bilat-
eral salpingo-oophorectomy (BSO) at age 40 years.
Kwon. Salpingectomy and BRCA Mutation Carriers. Obstet
Gynecol 2013.
respectively (relative risks of 0.40 and 0.20, respectively,
compared with a reference risk of 1.0 without surgery).
The benefit of additional oophorectomy after salpingec-
tomy yields an incremental cost-effectiveness ratio that
is well under $100,000 per quality-adjusted life-year
gained compared with salpingectomy alone. When the
relative risk of ovarian cancer from salpingectomy is
increased to 0.30 in a sensitivity analysis (while keeping
the relative risk unchanged at 0.20 for bilateral salpingo-
oophorectomy), the incremental cost-effectiveness ratio
is higher because magnitude of benefit from additional
oophorectomy is lower, but it is still under $100,000 per
quality-adjusted life-year gained.
We conducted a Monte Carlo simulation to
estimate the total number of breast and ovarian cancers
associated with each of the strategies as well as the
excess number of cardiovascular deaths secondary to
premenopausal bilateral salpingo-oophorectomy. In
Canada there are approximately 231,600 women
between the ages of 30 and 39 years.54 Assuming a pop-
ulation frequency of BRCA1 and BRCA2 germline
mutations of 0.32% and 0.69%, respectively,55 there
Kwon et al Salpingectomy and BRCA Mutation Carriers 19

Prophylactic salpingectomy
Prophylactic salpingectomy with
delayed oophorectomy
BSO
($1,000 per quality-adjusted life year)
Incremental cost-effectiveness ratio
160
140
120
100
80
60
40
20
0 End Points Study Group, approximately 60% of
0.2 0.3 0.4 0.5
Relative risk of ovarian cancer
after prophylactic salpingectomy
Fig. 3. Sensitivity analysis on relative risk of ovarian cancer
after salpingectomy. The incremental cost-effectiveness
ratio for prophylactic salpingectomy and delayed pro-
phylactic oophorectomy is sensitive to variations in the
relative risk of ovarian cancer after prophylactic sal-
pingectomy. The lower the relative risk of ovarian cancer
after prophylactic salpingectomy (that is, the greater the risk
reduction, with a greater proportion of these cancers arising
in the fallopian tube), the smaller the benefit of additional
oophorectomy in terms of net health benefit (quality-
adjusted life expectancy), which increases the incremental
cost-effectiveness ratio. BSO, bilateral salpingo-oophorectomy.
Kwon. Salpingectomy and BRCA Mutation Carriers. Obstet
Gynecol 2013.
are an estimated 700 BRCA1 and 1,600 BRCA2 muta-
tion carriers in this age group. By simulating this
cohort, bilateral salpingo-oophorectomy at age 40
years offers the greatest risk reduction against breast
and ovarian cancer with at least a 20% lower risk of
ovarian cancer and up to a 40% lower risk of breast
cancer compared with salpingectomy alone. Although
there are more deaths from cardiovascular disease after
bilateral salpingo-oophorectomy compared with the
other two strategies, the overall mortality rate is less
than 1%. These results are summarized in Table 3.
DISCUSSION
The results of this analysis suggest that bilateral
salpingectomy followed by delayed oophorectomy
may be a reasonable option for BRCA mutation carriers
20 Kwon et al Salpingectomy and BRCA Mutation Carriers
when quality of life is taken into account and bilateral
salpingo-oophorectomy is considered unacceptable.
Salpingectomy by itself does not appear to be an
appropriate recommendation, because it has no effect
on breast cancer risk nor does it appear to provide
the same magnitude of benefit as bilateral salpingo-
oophorectomy in reducing ovarian cancer risk. Salpin-
gectomy followed by delayed oophorectomy appears to
improve quality-adjusted life expectancy compared
with bilateral salpingo-oophorectomy alone; however,
quality of life after bilateral salpingo-oophorectomy
could be improved with short-term use of hormone
therapy, which does not appear to increase breast
cancer risk in these high-risk women.56,57 In our base
case analysis, we assumed that women who had pro-
phylactic bilateral salpingo-oophorectomy did not use
hormone therapy; therefore, we may have underesti-
mated their quality-adjusted life expectancy. According
to the Prevention and Observation of Surgical
0.6 women use hormone therapy after prophylactic bilat-
eral salpingo-oophorectomy.57 Our analysis suggests
that, if the utility of bilateral salpingo-oophorectomy is
increased to 0.93 (possibly after hormone therapy), the
quality-adjusted life expectancy of bilateral salpingo-
oophorectomy exceeds that of prophylactic salpingec-
tomy followed by delayed oophorectomy. Finally,
oophorectomy appears to reduce breast cancer risk in
both premenopausal and postmenopausal women,58
which implies a net health benefit of this intervention
regardless of age.
Several studies have reported the identification of
either invasive high-grade serous carcinomas of the
fallopian tube or serous tubal intraepithelial carcinomas
in prophylactic bilateral salpingo-oophorectomy speci-
mens from women with BRCA germline mutations with
the majority of pathologic abnormalities attributable to
fallopian tube carcinomas or precursor lesions.9–20
However, there is still uncertainty about the true pro-
portion of BRCA-associated ovarian cancers that arise
primarily in the fallopian tube, because reported
findings have ranged considerably from 18.8% to
100%.9–11,13,15,17,18,20,36 There also remain limited data
on short- and long-term outcomes of salpingectomy.
There are no studies directly comparing prophylactic
salpingectomy with bilateral salpingo-oophorectomy
for these high-risk women. The only published data
on this topic to date include an editorial from Greene
et al,59 who suggest that “bilateral salpingectomy with
ovarian retention” be considered “an investigational
risk management option of unproven clinical useful-
ness,” an opinion article from Dietl et al,60 who propose
that bilateral salpingectomy “is likely to reduce the risk
OBSTETRICS & GYNECOLOGY
Table 3. Monte Carlo Simulation of 700 and 1,600 Women With BRCA1 and BRCA2 Mutations,
Respectively, From Age 30–39 Years in Canada
Estimated No. With Breast
Cancer (% Risk Reduction
Compared With Prophylactic
[Bilateral] Salpingectomy at
Testing Strategy Age 40 y Alone)
BRCA1 (n5700)
Prophylactic (bilateral) 274
salpingectomy at age 40 y
Prophylactic salpingectomy 273 (Y0.4%)
at age 40 y, prophylactic
oophorectomy at age 50 y
Bilateral salpingo-oophorectomy 212 (Y22.6%)
at age 40 y
BRCA2 (n51,600)
Prophylactic (bilateral) 549
salpingectomy at age 40 y
Prophylactic salpingectomy at 543 (Y1.1%)
age 40 y, prophylactic
oophorectomy at age 50 y
Bilateral salpingo-oophorectomy 331 (Y39.7%)
at age 40 y
for pelvic carcinomas,” and a feasibility study by Leb-
lanc et al,61 in which radical fimbriectomy is postulated
as a reasonable risk-reducing intervention in BRCA
mutation carriers who are reluctant to undergo bilateral
salpingo-oophorectomy. A clinical trial led by Leblanc
et al62 is currently recruiting young BRCA mutation
carriers for radical fimbriectomy (NCT016808074),
but it is not expected to be complete until 2019.
The advantage of this analysis is that we can
promptly estimate the costs and benefits of different
risk-reducing strategies among women with BRCA
mutations, which would be difficult to evaluate in the
context of a clinical trial. The major disadvantage is that
it simulates a hypothetical cohort, and there is uncer-
tainty relating to various parameters such as the extent
of risk reduction from salpingectomy, quality of life
after different surgical strategies, and health care costs.
However, we have accounted for these uncertainties
with extensive sensitivity analyses and evaluated these
parameters within a wide range of estimates. It is impor-
tant to note that these results apply only to BRCA muta-
tion carriers and not to 1) untested relatives of carriers;
2) those with uninformative testing; or 3) those with
a family history to suggest increased risk. We also did
not model BRCA mutation carriers with a history of
breast cancer, although these women may still be at risk
for ovarian cancer and they comprise almost 25% of all
referrals to our Hereditary Cancer Program.46 Many of
these women would have received anthracycline- and
taxane-based chemotherapy, but the likelihood of pre-
mature ovarian failure appears to be low, particularly for
VOL. 121, NO. 1, JANUARY 2013 Kwon et al
Estimated No. With Ovarian
Cancer (% Risk Reduction Estimated No. of
Compared With Prophylactic Deaths Attributed
[Bilateral] Salpingectomy to Cardiovascular
at Age 40 y alone) Disease
123 0
105 (Y14.6%) 0
95 (Y22.8%) 5
122 0
106 (Y13.1%) 0
97 (Y20.5%) 10
women younger than age 40 years,63–65 so there may
still be a role for salpingectomy as a risk-reducing strat-
egy. However, there seems to be less ambivalence about
bilateral salpingo-oophorectomy after their previous
cancer diagnosis, because a greater proportion of these
women undergo this procedure than unaffected
carriers.6 We did model BRCA1 and BRCA2 mutation
carriers separately because of the different cancer phe-
notypes. BRCA2 carriers have a lower lifetime risk of
ovarian cancer66 and therefore have a lower proportion
of ovarian cancer cases and cancer-related deaths. Any
reduction in cancer incidence and mortality (eg, from
delayed oophorectomy after salpingectomy) will appear
small when averaged over the entire cohort at risk (com-
pared with BRCA1 carriers). The smaller the average
incremental benefit, the higher the incremental cost-
effectiveness ratio. Salpingectomy with delayed oopho-
rectomy yields incremental cost-effectiveness ratios of
$37,805 and $89,680 per quality-adjusted life-year for
BRCA1 and BRCA2 carriers, respectively, compared
with salpingectomy alone. Despite the discrepancy, the
incremental cost-effectiveness ratios are still less than
$100,000 per quality-adjusted life-year, so this interven-
tion would be considered cost-effective for both BRCA1
and BRCA2 carriers.
It is important to emphasize that the standard of
care for women inheriting germline mutations in
BRCA1 or BRCA2 still remains prophylactic bilateral
salpingo-oophorectomy after completion of childbear-
ing or around the age of 40 years.2 It offers the greatest
risk reduction in breast and ovarian cancer compared
Salpingectomy and BRCA Mutation Carriers 21
with salpingectomy with or without delayed oophorec-
tomy. However, a significant proportion of women do
not undergo bilateral salpingo-oophorectomy,6,45 and
many choose surveillance alone for ovarian cancer
despite the limited benefit of existing screening
methods.67–71 Ovarian cancer drives the mortality rate
among BRCA mutation carriers,4 and therefore any
intervention that reduces ovarian cancer risk is likely
better than no intervention at all. Although it remains
to be validated prospectively, bilateral salpingectomy
with delayed oophorectomy may be a reasonable alter-
native to bilateral salpingo-oophorectomy, especially for
those who are reluctant to undergo the latter procedure
because of the potential effect on quality of life.
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