The n e w e ng l a n d j o u r na l of m e dic i n e

original article

Prophylactic Surgery to Reduce the Risk

of Gynecologic Cancers in the Lynch Syndrome
Kathleen M. Schmeler, M.D., Henry T. Lynch, M.D., Lee-may Chen, M.D.,
Mark F. Munsell, M.S., Pamela T. Soliman, M.D., Mary Beth Clark, M.S.W.,
Molly S. Daniels, M.S., Kristin G. White, B.S., Stephanie G. Boyd-Rogers, R.N.,
Peggy G. Conrad, M.S., Kathleen Y. Yang, M.D., Mary M. Rubin, Ph.D.,
Charlotte C. Sun, Dr.P.H., Brian M. Slomovitz, M.D.,
David M. Gershenson, M.D., and Karen H. Lu, M.D.

A bs t r ac t

Background
Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have a From the Departments of Gynecologic On-
40 to 60 percent lifetime risk of endometrial cancer and a 10 to 12 percent lifetime cology (K.M.S., P.T.S., K.G.W., S.G.B.-R.,
C.C.S., B.M.S., D.M.G., K.H.L.), Biostatis-
risk of ovarian cancer. The benefit of prophylactic gynecologic surgery for women tics and Applied Mathematics (M.F.M.),
with this syndrome has been uncertain. We designed this study to determine the and Clinical Cancer Genetics (M.S.D.), the
reduction in the risk of gynecologic cancers associated with prophylactic hysterec- University of Texas M.D. Anderson Cancer
Center, Houston; the Department of Pre-
tomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome. ventive Medicine, Creighton University,
Omaha, Nebr. (H.T.L., M.B.C.); and the
Methods Departments of Gynecologic Oncology
(L.C., K.Y.Y., M.M.R.) and Medicine (P.G.C.),
Three hundred fifteen women with documented germ-line mutations associated University of California at San Francisco,
with the Lynch syndrome were identified. Women who had undergone prophylactic San Francisco. Address reprint requests to
hysterectomy (61 women) and women who had undergone prophylactic bilateral Dr. Lu at the Department of Gynecologic
Oncology, University of Texas M.D. Ander-
salpingo-oophorectomy (47 women) were matched with mutation-positive women son Cancer Center, P.O. Box 301439, Unit
who had not undergone the procedure in question (210 women for the analysis of 1362, Houston, TX 77230-1439, or at khlu@
endometrial cancer and 223 for the analysis of ovarian cancer). Women who had mdanderson.org.
undergone prophylactic surgery and their matched controls were followed from the N Engl J Med 2006;354:261-9.
date of the surgery until the occurrence of cancer or until the data were censored Copyright © 2006 Massachusetts Medical Society.
at the time of the last follow-up visit.

Results
There were no occurrences of endometrial, ovarian, or primary peritoneal cancer
among the women who had undergone prophylactic surgery. Endometrial cancer
was diagnosed in 69 women in the control group (33 percent), for an incidence
density of 0.045 per woman-year, yielding a prevented fraction (the proportion of
potential new cancers prevented) of 100 percent (95 percent confidence interval, 90
to 100 percent). Ovarian cancer was diagnosed in 12 women in the control group
(5 percent), for an incidence density of 0.005 per woman-year, yielding a prevented
fraction of 100 percent (95 percent confidence interval, −62 to 100 percent).

Conclusions
These findings suggest that prophylactic hysterectomy with bilateral salpingo-oopho-
rectomy is an effective strategy for preventing endometrial and ovarian cancer in
women with the Lynch syndrome.

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 The n e w e ng l a n d j o u r na l
T
he Lynch syndrome (hereditary non-
polyposis colorectal cancer) is an autoso-
mal dominant cancer-susceptibility syn-
drome caused by a germ-line mutation in one of
the DNA-mismatch repair genes.1-4 It is associ-
ated with an early onset of cancer and the devel-
opment of multiple types of cancer, including can-
cer of the colon and rectum, endometrium, ovary,
small bowel, ureter, and renal pelvis. The lifetime
risk of endometrial cancer for women with the
Lynch syndrome is 40 to 60 percent, which equals
or exceeds their risk of colorectal cancer. In addi-
tion, they have a 10 to 12 percent lifetime risk of
ovarian cancer.5,6
Up to the present, data have been lacking on
the basis of which to evaluate the efficacy of
gynecologic surgery performed to reduce the risk
of cancer in women with the Lynch syndrome.
In 1997, the Cancer Genetics Studies Consor-
tium reviewed the available evidence regarding
the efficacy of prophylactic hysterectomy and bi-
lateral salpingo-oophorectomy and published a
consensus statement concluding that there was
insufficient evidence for it to recommend wheth-
er or not women with the Lynch syndrome should
have prophylactic surgery to reduce the risk of
gynecologic cancer.7 Despite the lack of evidence,
several authors have suggested that hysterectomy
with bilateral salpingo-oophorectomy is a reason-
able preventive strategy for women with the
Lynch syndrome, after they have completed child-
bearing.8-10 We conducted a study to determine
whether the risk of gynecologic cancers among
women with the Lynch syndrome was reduced
after hysterectomy and bilateral salpingo-oopho-
rectomy.
Me thods
Study patients
Approval for this study, with a waiver of informed
consent, was obtained from the institutional re-
view board at each of the participating institu-
tions. The records of patients enrolled in heredi-
tary-cancer registries from 1973 to 2004 were
reviewed. We identified 380 women with docu-
mented MLH1, MSH2, or MSH6 germ-line muta-
tions from registries at Creighton University (284
women), the University of Texas M.D. Anderson
Cancer Center (72 women), and the University of
California at San Francisco (24 women). Women
with genetic variants of unknown functional sig-
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of m e dic i n e
nificance were excluded. The study was based on
the 315 women (83 percent of the total) for whom
follow-up information was available.
Registry databases and patients’ medical rec-
ords were reviewed to obtain information on
demographic characteristics, genetic testing re-
sults, and vital status. Surgical information and
occurrences of cancer were verified by reviews of
medical records, operative notes, and pathology
reports.
Endometrial Cancer
To determine whether prophylactic surgery re-
duced the risk of endometrial cancer, we performed
a retrospective cohort analysis of women with
germ-line mutations. In this analysis, we com-
pared the outcome among those who had under-
gone hysterectomy either to prevent cancer or to
treat benign conditions with the outcome among
women who had not undergone hysterectomy
(controls). We matched each woman who had un-
dergone hysterectomy with one or more control
women by a method similar to that used by Reb-
beck et al.11 Control women were of similar age
to the women with whom they were matched
(i.e., their dates of birth were within five years of
each other), had been treated at the same institu-
tions, and had been alive, with an intact uterus
and no history of gynecologic cancer, at the time
the women with whom they were matched under-
went hysterectomy. Sixty-one women who had un-
dergone hysterectomy, with or without salpingo-
oophorectomy, were matched with 210 controls.
Forty-four potential controls could not be matched
with case women because their dates of birth did
not fall within five years of that of any woman
who had undergone hysterectomy, and therefore
they were not included in the analysis.
Ovarian Cancer
We performed a similar analysis to evaluate the
reduction in the risk of ovarian cancer after pro-
phylactic surgery. Women who had undergone
bilateral salpingo-oophorectomy for preventive
reasons or to treat benign conditions were matched
with one or more mutation-positive control wom-
en who were of similar age (date of birth within
five years), had been treated at the same institu-
tion, had not undergone prophylactic bilateral
salpingo-oophorectomy, and had been alive, with
both ovaries intact and no history of gynecologic
cancer, at the time the women with whom they
www.nejm.org january 19, 2006
 Prophylactic Surgery in Women with the Lynch Syndrome

were matched underwent bilateral salpingo-oopho-
rectomy. On the basis of these criteria, 47 women
who had undergone prophylactic bilateral sal-
pingo-oophorectomy were matched with 223 con-
trols. Forty-five potential controls could not be
matched with case women because their dates of
birth did not fall within five years of that of any
woman who had undergone bilateral salpingo-
oophorectomy, and therefore they were not in-
cluded in the analysis.
Statistical Analysis
The women who had undergone prophylactic
surgery and the controls were followed from the
date of the prophylactic surgery until the occur-
rence of endometrial, ovarian, or primary perito-
neal cancer or until the observations were cen-
sored as of the date of death or the date of the
last contact. The primary end point was the de-
velopment of endometrial, ovarian, or primary
peritoneal cancer. The incidence density12 (the
number of cancers divided by the number of
years the women were at risk) was calculated for
endometrial, ovarian, and primary peritoneal
cancer in each group. The prevented fraction12
([incidence density for controls − incidence density
for women who underwent surgery] ÷ [incidence
density for controls]), or the proportion of poten-
tial new cancers prevented, was estimated with
the 95 percent confidence interval. The cumula-
tive incidence of cancer was estimated by the
method of Kaplan and Meier.13 All analyses were
performed with Stata (version 8.0) and S-PLUS
2000 software.
R e sult s
Of the 315 women with germ-line mutations, 61
(19 percent) underwent gynecologic surgery for
preventive reasons or to treat benign conditions.
Forty-seven of these women underwent both hys-
terectomy and bilateral salpingo-oophorectomy,
and 14 women underwent hysterectomy only.
None of the women in our study underwent bilat-
eral salpingo-oophorectomy without hysterecto-
my. Thirty-eight percent had genetic testing before
undergoing prophylactic surgery. The characteris-
tics of the entire study population are shown in
Table 1. There were no significant differences
among the participating institutions in the pro-
portion of women who underwent prophylactic
surgery. There were also no significant differences
in the proportions of women with MLH1, MSH2,
or MSH6 mutations between the group of women
who underwent prophylactic surgery and the group
who did not. Eighty-five percent of the women
who had undergone prophylactic surgery, and 82
percent of the women who had not, were parous.

Table 1. Characteristics of the 315 Women in the Study Population.

Prophylactic Surgery No Prophylactic Surgery

Characteristic (N = 61)* (N = 254) P Value
number (percent)

Institution where treated 0.66

Creighton University (N = 219) 43 (20) 176 (80)
University of Texas M.D. 12 (17) 60 (83)
Anderson Cancer Center (N = 72)
University of California at 6 (25) 18 (75)
San Francisco (N = 24)
Parity ≥1† 40 (85) 145 (82) 0.83
Mutation
MLH1 29 (48) 108 (43)
MSH2 31 (51) 143 (56)
MSH6 0 3 (1)
MLH1 and MSH2 1 (2) 0 0.15

* Prophylactic surgery was defined as hysterectomy, with or without bilateral salpingo-oophorectomy, performed for the
prevention of disease or for the treatment of a benign condition.
† Information on parity was available for 223 of 315 patients.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Endometrial Cancer
Of the women who underwent prophylactic hys-
terectomy, none subsequently had endometrial
cancer, as compared with 69 women (33 percent)
in the control group (Table 2). The incidence den-
sity was 0.000 per woman-year for the women
who underwent prophylactic hysterectomy and
0.045 per woman-year for the controls (P<0.001),
yielding a prevented fraction of 100 percent (95
percent confidence interval, 90 to 100 percent).
The cumulative incidence of endometrial cancer
for each group is illustrated in Figure 1. The me-
dian age at prophylactic hysterectomy was 41 years
(range, 20 to 63), and the median age at the diag-
nosis of endometrial cancer was 46 years (range,
30 to 69). Four endometrial cancers (6 percent)
were diagnosed in women under 35 years of age.
The women who underwent prophylactic hyster-
ectomy were followed for an average of 13.3 years
(range, 0.5 to 38.0) after surgery, and the con-
trols were followed for an average of 7.4 years
(range, 0.1 to 35.0) after the time of the matched
woman’s surgery. The distribution of patients ac-
cording to the stage of endometrial cancer at di-
agnosis is shown in Table 2.
Among women who did not undergo prophy-

Table 2. Reduction in the Risk of Endometrial Cancer after Prophylactic Hysterectomy.*

Prophylactic Hysterectomy No Prophylactic Hysterectomy
Variable (N = 61) (N = 210)
Cases of endometrial cancer — no. (%) 0 69 (33)
Age at surgery — yr
Median 41 NA
Range 20–63 NA
Distribution of ages at surgery — no. (%)
≤35 Yr 14 (23) NA
36–40 Yr 15 (25) NA
41–45 Yr 17 (28) NA
>45 Yr 15 (25) NA
Age at diagnosis of cancer — yr
Median NA 46
Range NA 30–69
Distribution of ages at diagnosis — no. (%)
≤35 Yr NA 4 (6)
36–40 Yr NA 8 (12)
41–45 Yr NA 22 (32)
>45 Yr NA 35 (51)
Cancer stage at diagnosis — no. (%)
I NA 48 (70)
II NA 4 (6)
III NA 6 (9)
IV NA 0 (0)
Unknown NA 11 (16)
Follow-up — yr
Mean 13.3 7.4
Range 0.5–38.0 0.1–35.0
Total no. of woman-yr 814 1549
Incidence density (cases/woman-yr)† 0.000 0.045

* NA denotes not applicable.

† P<0.001. The prevented fraction is 100 percent (95 percent confidence interval, 90 to 100 percent).

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 Prophylactic Surgery in Women with the Lynch Syndrome
lactic hysterectomy, endometrial cancer developed
in 22 of those who had an MLH1 mutation (28
percent), 47 of those with an MSH2 mutation (37
percent), and none of those with an MSH6 muta-
tion. The differences among these figures are not
statistically significant. Ninety-two percent of the
patients underwent genetic testing after receiving
a diagnosis of endometrial cancer. Endometrial
cancers were incidentally diagnosed in three
women at the time of prophylactic hysterectomy.
Two of the patients had stage I disease and one
patient had stage II disease. They underwent sur-
gery at 38, 58, and 48 years of age, respectively,
and are currently alive, without any evidence of
disease, 27, 2, and 4 years after surgery.
At the time of the analysis, 25 women (9 per-
cent) had died. Twenty-two of these women (10
percent) were from the control group and three
(5 percent) had undergone prophylactic surgery.
The causes of death among the women in the con-
trol group were endometrial cancer (three women),
ovarian and colon cancer (one woman), colon can-
cer (seven women), other Lynch syndrome–related
cancers (four women), other cancers (two women),
cardiac disease (one woman), and unknown (four
women). The causes of death for the three women
who underwent prophylactic surgery were colon
cancer, brain cancer, and bladder cancer.
Ovarian Cancer
Of the 47 women who had undergone bilateral
salpingo-oophorectomy at the time of their hys-
terectomy for cancer prevention or for benign con-
ditions, none subsequently had ovarian cancer,
as compared with 12 of the controls (5 percent)
(Table 3). One of the women who had ovarian can-
cer had previously undergone hysterectomy for
a benign condition without bilateral salpingo-
oophorectomy. The incidence density was 0.000
per woman-year for the women who had under-
gone surgery and 0.005 per woman-year for the
controls (P = 0.09). The prevented fraction was
100 percent (95 percent confidence interval, −62 to
100 percent). The cumulative incidence of ovarian
cancer for each group is illustrated in Figure 2.
The median age at prophylactic bilateral sal-
pingo-oophorectomy was 41 years (range, 20 to
58), and the median age at the diagnosis of ovar-
ian cancer was 42 years (range, 31 to 48). Two
(17 percent) of the ovarian cancers were diagnosed
in women before the age of 35. The average fol-
low-up was 11.2 years (range, 0.5 to 38.0) after
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1.0
Incidence of Endometrial Cancer
0.8
No hysterectomy
0.6
0.4
0.2
Hysterectomy
0.0
0 5 10 15 20
Years
No. at Risk
No hysterectomy 210 106 52 28 20
Hysterectomy 61 39 28 25 18
Figure 1. Cumulative Incidence of Endometrial Cancer among Women
with the Lynch Syndrome Who Underwent Prophylactic Hysterectomy
and Those Who Did Not.
surgery among women who had undergone pro-
phylactic bilateral salpingo-oophorectomy and 10.6
years (range, 0.1 to 41.0) after the time of the
matched woman’s surgery among the control wom-
en. The distribution of women according to the
stage of ovarian cancer at diagnosis is shown in
Table 3.
Among the women who did not undergo pro-
phylactic bilateral salpingo-oophorectomy, ovar-
ian cancer developed in five of those with an
MLH1 mutation (6 percent), seven of those with
an MSH2 mutation (5 percent), and none of those
with an MSH6 mutation (P not significant). None
of the women who underwent prophylactic hys-
terectomy with bilateral salpingo-oophorectomy
subsequently had primary peritoneal cancer. Of
the 12 cases of ovarian cancer, 3 (25 percent)
were synchronous primary cancers of the ovary
and endometrium according to the criteria of
Scully et al.14 No cases of ovarian cancer were
incidentally diagnosed at the time of prophylac-
tic bilateral salpingo-oophorectomy.
Surgical Complications
Surgical complications were noted in 1 of the 61
women who underwent prophylactic surgery (1.6
percent). The patient was a 27-year-old woman
who had received a diagnosis of rectal carcinoma
two years previously and had been treated by rec-
tosigmoid resection with colostomy and creation
of a Hartmann’s pouch, followed by radiation
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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 3. Reduction in the Risk of Ovarian Cancer after Prophylactic Bilateral Salpingo-Oophorectomy.*

Prophylactic Bilateral No Prophylactic Bilateral

Salpingo-oophorectomy Salpingo-oophorectomy
Variable (N = 47) (N = 223)
Cases of ovarian cancer — no. (%) 0 12 (5.5)
Age at surgery — yr
Median 41 NA
Range 20–58 NA
Distribution of ages at surgery — no. (%)
≤35 Yr 10 (21) NA
36–40 Yr 14 (30) NA
41–45 Yr 10 (21) NA
>45 Yr 13 (28) NA
Age at diagnosis of cancer — yr
Median NA 42
Range NA 31–48
Distribution of ages at diagnosis — no. (%)
≤35 Yr NA 2 (17)
36–40 Yr NA 3 (25)
41–45 Yr NA 4 (33)
>45 Yr NA 3 (25)
Cancer stage at diagnosis — no. (%)
I NA 5 (42)
II NA 3 (25)
III NA 2 (17)
IV NA 0 (0)
Unknown NA 2 (17)
Follow-up — yr
Mean 11.2 10.6
Range 0.5–38.0 0.1–41.0
Total no. of woman-yr 526 2364
Incidence density (cases/woman-yr)† 0.000 0.005

* NA denotes not applicable.

† P = 0.09. The prevented fraction is 100 percent (95 percent confidence interval, –62 to 100 percent).

therapy. At the time of prophylactic abdominal had synchronous (3 patients) or metachronous

hysterectomy with bilateral salpingo-oophorec- (38 patients) colorectal cancer and endometrial
tomy, a ureteral injury occurred and was repaired. or ovarian cancer (32 and 9 patients, respective-
The patient subsequently had a ureterovaginal ly). The median age at the diagnosis of colorectal
fistula as well as a ureteroenteral fistula to the cancer was 47 years (range, 26 to 77). Five of the
Hartmann’s pouch and underwent a ureteroneo- 41 women (12 percent) were 35 years old or young-
cystostomy. She later had a rectovaginal fistula, er, 6 (15 percent) were 36 to 40 years of age, 5 (12
which she decided not to have repaired. percent) were 41 to 45 years of age, and 25 (61
percent) were over the age of 45. Twenty-one of
Metachronous Colorectal these 41 women (51 percent) received a diagnosis
and Endometrial or Ovarian Cancer of gynecologic cancer after receiving a diagno-
In our cohort, 107 women (34 percent) received a sis of and undergoing surgery for colorectal can-
diagnosis of colorectal cancer. Forty-one patients cer. The median time between the diagnoses of

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 Prophylactic Surgery in Women with the Lynch Syndrome

colon cancer and gynecologic cancer was 5 years hysterectomy and bilateral salpingo-oophorec-
(range, 1 to 25). tomy are bleeding, infection, and injuries to the
urinary tract and bowel. In our study, the surgi-
Dis cus sion cal complication rate was 1.6 percent. This fig-
ure is consistent with previously published com-
This study provides evidence of a benefit of pro- plication rates of 1 to 9 percent associated with
phylactic hysterectomy and bilateral salpingo- hysterectomy and bilateral salpingo-oophorec-
oophorectomy in preventing gynecologic cancers tomy for benign conditions.20-22 In premenopausal
in women with the Lynch syndrome. In our co- women, bilateral salpingo-oophorectomy results
hort, there were no new cases of endometrial or in premature menopause, with attendant symp-
ovarian cancer among the women who underwent toms (including hot flashes, vaginal dryness,
prophylactic surgery. The reduction in the num- sexual dysfunction, and sleep disturbances) and
ber of cancer cases was statistically significant an increased risk of osteoporosis.23-25 Many of
for endometrial cancer but not for ovarian can- these conditions can usually be managed with
cer; however, the power of the latter comparison hormonal or nonhormonal medications.26 Infor-
was limited by the small number of ovarian can- mation regarding these side effects was not avail-
cers diagnosed in our cohort. able for our cohort.
The median age at diagnosis was 46 years None of the women in our cohort received a
for endometrial cancer and 42 years for ovarian diagnosis of primary peritoneal cancer after pro-
cancer. These numbers are consistent with those phylactic bilateral salpingo-oophorectomy; how-
in previous studies of women with the Lynch ever, our sample size and follow-up time were
syndrome that have found a mean age at diagno- limited. Previous studies involving women with
sis of 48 to 49 years for endometrial cancer15,16 BRCA mutations have reported an incidence of
and 42 years for ovarian cancer,17 with the ma- primary peritoneal cancer after prophylactic bi-
jority of cancers diagnosed in women after the lateral salpingo-oophorectomy of 0.8 to 1.0 per-
age of 35. These findings support consideration cent.11,27 The risk of primary peritoneal cancer
of prophylactic hysterectomy and bilateral sal- among women with the Lynch syndrome after
pingo-oophorectomy in women with the Lynch prophylactic bilateral salpingo-oophorectomy re-
syndrome after the age of 35, or once childbear- mains uncertain.
ing has been completed. Three women who underwent prophylactic
There is currently limited information on the hysterectomy were found to have occult endome-
efficacy of surveillance in reducing the risk of trial carcinomas at the time of surgery. This find-
endometrial and ovarian cancer in women with ing emphasizes the need to maintain a high in-
the Lynch syndrome.18,19 Current screening guide- dex of suspicion during prophylactic surgery in
lines for gynecologic cancer recommend annual women with the Lynch syndrome.28 Preopera-
pelvic examinations, transvaginal ultrasonogra- tive assessment with endometrial biopsy, trans-
phy, endometrial biopsy, and measurements of vaginal ultrasonography, and measurement of
serum CA-125 levels beginning at 25 to 35 years CA-125 levels should be considered. The uterus
of age,7 but controlled studies are lacking to and ovaries should be carefully assessed at the
support these methods in young premenopausal time of surgery; the pathologist should be ad-
women. Information regarding screening for en- vised of the high risk of endometrial and ovarian
dometrial and ovarian cancer was not available cancer, and the specimens should be carefully
for our cohort. Further research is needed to de- examined intraoperatively, with frozen sections
termine the efficacy of these screening methods obtained if indicated. The surgeon should be pre-
in comparison with prophylactic surgery in reduc- pared to perform a complete staging operation,
ing morbidity and mortality from endometrial if necessary.
and ovarian cancer in women with the Lynch syn- In our cohort, 41 of 315 women (13 percent)
drome. received a diagnosis of synchronous or metachro-
The disadvantages of prophylactic hysterec- nous colorectal cancer and endometrial or ovar-
tomy and bilateral salpingo-oophorectomy include ian cancer. Thirty-six of these women (88 per-
surgical complications and premature menopause. cent) were older than 35 years at the time of their
The most common complications associated with diagnosis of colorectal cancer. In 21 of these

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 The n e w e ng l a n d j o u r na l of m e dic i n e

cant differences in the incidence of endometrial

0.5 or ovarian cancer among women with MLH1,
MSH2, and MSH6 mutations, but the power of this
Incidence of Ovarian Cancer

0.4 analysis was limited by our small sample size.

A limitation of our study is that the data were
0.3 collected retrospectively. Many of the women in
our cohort underwent prophylactic surgery or
0.2 received a diagnosis of cancer before they had
No BSO undergone genetic testing. We did not have in-
0.1 formation on body-mass index or other risk fac-
BSO tors for gynecologic cancers. In addition, we were
0.0 unable to assess the effects of prophylactic sur-
0 5 10 15 20
gery on survival and on deaths related to gyne-
Years
cologic cancer. Further studies with longer follow-
No. at Risk
No BSO 223 131 83 65 50 up will be needed to assess the differences in
BSO 47 28 19 16 11 survival between women who undergo prophy-
Figure 2. Cumulative Incidence of Ovarian Cancer among Women lactic gynecologic surgery and those who do not.
with the Lynch Syndrome Who Underwent Prophylactic Bilateral Salpingo- In summary, this study provides evidence of
Oophorectomy (BSO) and Those Who Did Not. the efficacy of prophylactic surgery in preventing
gynecologic cancers in women with the Lynch
syndrome. Preoperative counseling should ad-
women, the gynecologic cancer was diagnosed dress the trade-offs between the reduction in the
after the woman had undergone treatment for risk of cancer and the risks and side effects of
colorectal cancer and could have been prevented surgery, as well as the uncertainties regarding
if prophylactic hysterectomy and bilateral sal- surveillance of gynecologic cancer as an alterna-
pingo-oophorectomy had been performed at the tive management approach.
time of surgery for colorectal cancer. Supported in part by a grant from the National Cancer Institute
(N01-CN-05127).
Vasen et al.15 evaluated the lifetime cancer No potential conflict of interest relevant to this article was re-
risks associated with different gene mutations in ported.
138 families in which the Lynch syndrome oc- We are indebted to Dr. Patrick M. Lynch, Dr. Russell R. Broaddus,
and the Lynch syndrome registry at the University of Texas M.D.
curred. They found the risks of both endome- Anderson Cancer Center; to Mrs. Jane F. Lynch, Mr. William C.
trial cancer and ovarian cancer to be higher in Dowart, and the Creighton University Lynch syndrome registry; and
MSH2 mutation carriers than in MLH1 mutation to Dr. Jonathan P. Terdiman, Ms. Amie M. Blanco, and the University
of California at San Francisco Colorectal Cancer Prevention Program
carriers, but the differences were not statistically Familial Gastrointestinal Cancer Registry.
significant. Similarly, we did not detect signifi-

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