Managemen of Woman with High Risk Ovarian Cancer

Management of Women at High Risk for Ovarian Cancer
The management of a woman with a strong family history of epithelial ovarian
cancer must be individualized and depends on her age, her reproductive plans, and
the extent of risk. In all of these syndromes, women at risk benefit from a thorough
pedigree analysis. A geneticist should evaluate the family pedigree for at least three
generations. Decisions about management are best made after careful study and,
whenever possible, verification of the histologic diagnosis of the family members' ovarian cancer.
The value of testing for BRCA1 and BRCA2 has been clearly established, and there
are guidelines for testing (54,59,61). The importance of genetic counseling cannot
be overemphasized because the decision is complex. The American Society of Clinical Oncology
has offered guidelines that emphasize careful evaluation by geneticists, careful maintenance
of medical records, and a clear understanding in a genetic screening clinic of how to counsel
and manage these patients. Concerns remain over how the information should be used, the
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impact on insurability, how the results will be interpreted, and how the information will be
used within a specific family (e.g., to counsel children).
Although there are some conflicting data, the behavior of breast cancers arising in women
with germline mutations in BRCA1 or BRCA2 is comparable to that of sporadic tumors (53).
Women with breast cancer who carry these mutations, however, are at a greatly
increased risk of ovarian cancer as well as a second breast cancer: the lifetime risk
of ovarian cancer is 54% for women who have a BRCA1 mutation and 23% for those
with a BRCA2 mutation, and for the two groups together, there is an 82% lifetime risk
of breast cancer (62).
Although recommended by the National Institutes of Health Consensus Conference
on Ovarian Cancer (63), the value of screening with transvaginal ultrasonography,
CA125 levels, or other procedures has not been clearly established in women at high
risk. Bourne and co-workers (49) have shown that, using this approach, tumors can be
detected approximately 10 times more often than in the general population, and thus
they recommend screening in high-risk women.
Data derived from a multicenter consortium of genetic screening centers indicate that
the use of the oral contraceptive pill is associated with a lower risk for development
of ovarian cancer in women who have a mutation in either BRCA1 or BRCA2 (64). The
risk reduction is significant: in women who have taken oral contraceptives for 5 or more years,
the relative risk of ovarian cancer is 0.4, or a 60% reduction in the incidence of the disease.
Prophylactic Oophorectomy in High-risk Women
The value of prophylactic salpingo-oophorectomy in these patients has been
documented (65,66,67,68,69,70,71). Women at high risk for ovarian cancer who
undergo prophylactic oophorectomy have a risk of harboring occult neoplasia: in one series of
98 such operations, 3 (3.1%) patients had a low-stage ovarian malignancy (67). The
protection against ovarian cancer is excellent: the performance of a prophylactic
salpingo-oophorectomy reduced the risk of BRCA-related gynecologic cancer by 96%
(68). Although the risk of ovarian cancer is significantly diminished, there remains the small risk
of peritoneal carcinoma, a tumor for which women who have mutations in BRCA1 and BRCA2
may have a higher predisposition. In these series, the subsequent development of peritoneal
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carcinoma was 0.8% and 1 %, respectively (66,67). In addition, the risk of
developing subsequent breast cancer was reduced by 50% to 80%. Women at high risk
for ovarian cancer who undergo prophylactic oophorectomy have a risk of harboring
occult neoplasia. In one series of 42 such operations, four patients (9.5%) had a malignancy, one
of which was noted at surgery and three that were microscopic; all were smaller than 5 mm (66).
The role of hysterectomy is more controversial. Although most studies show no increase in
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the rate of uterine and cervical tumors, there are some reports of an increase of papillary
serous tumors of the endometrium (71). Women on tamoxifen are at higher risk for
benign endometrial lesions (e.g., polyps) and endometrial cancer. Therefore, it is reasonable
to consider the performance of a prophylactic hysterectomy in conjunction with
salpingo-oophorectomy, and this decision should be individualized.
The survival of women who have a BRCA1 or BRCA2 mutation and develop ovarian cancer is
longer than that for those who do not have a mutation. In one study, the median survival
for mutation carriers was 53.4 months compared with 37.8 months for those with sporadic
ovarian cancer from the same institution (72).
Recommendations
Current recommendations for management of women at high risk for ovarian cancer
are summarized as follows (61,63,70):
●
Women who appear to be at high risk for ovarian or breast cancer should undergo
genetic counseling and, if the risk appears to be substantial, may be offered
genetic testing for BRCA1and BRCA2.
●
Women who wish to preserve their reproductive capacity can undergo screening
by transvaginal ultrasonography every 6 months, although the efficacy of this approach is
not clearly established.
●
Oral contraceptives should be recommended to young women before they embark on
an attempt to have a family.
●
Women who do not wish to maintain their fertility or who have completed their
families should be recommended to undergo prophylactic bilateral
salpingo-oophorectomy. The risk should be clearly documented, preferably established by
BRCA1 and BRCA2 testing, before oophorectomy is performed. These women should be
counseled that this operation does not offer absolute protection, because peritoneal
carcinomas occasionally can occur after bilateral oophorectomy (19,22,71).
●
In women who also have a strong family history of breast or ovarian cancer,
annual mammographic screening should be performed beginning at age 30 years.
●
Women with a documented HNPCC syndrome should be treated as above, but in
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addition, they should undergo periodic screening mammography, colonoscopy,
and endometrial biopsy (60,68).