Prophylactic Surgery in Hereditary Breast/Ovarian Cancer Syndrome
Prophylactic Surgery in Hereditary Breast/Ovarian Cancer Syndrome
The ability to identify a woman
with a germ-line mutation in
BRCA1 or BRCA2, through
clinical genetic testing, allows that
woman's physician to implement preventive
strategies that may spare her
from developing breast or ovarian
cancer. Unfortunately, the most effective
strategies currently are also the
most drastic; namely, prophylactic
mastectomy and/or prophylactic
That high-risk women would even
consider prophylactic surgery is directly
related to their high likelihood
of developing cancer. While the lifetime
risk of breast cancer in the general
population is 13.4%, in a BRCA1 mutation
carrier, it ranges from 50% to
80%.[1-4] Similarly, the lifetime risk
of ovarian cancer in the general population
is 1.7%, and in BRCA1 mutation
carriers, it is 20% to 40%.[1-4]
For BRCA2 mutation carriers, the estimates
for breast and ovarian cancer
risk remain substantially above those
of the general population but slightly
lower than those for BRCA1 mutation
Importance of Genetic
For physicians who manage highrisk women, the importance of genetic counseling and genetic testing cannot be overemphasized. Clinical genetic testing allows a substantially more precise estimate of a woman's risk of breast and/or ovarian cancer than family history alone. Women who test positive for a deleterious BRCA1 or BRCA2 mutation need appropriately aggressive management for the prevention and/or early detection of breast and ovarian cancer. Women who test negative for a known deleterious mutation in their family ("true negatives") can be reassured that they are not at increased risk of breast and/ or ovarian cancer, despite the substantial family history. Consider a parent with a known BRCA mutation: Each child has a 50/50 chance of inheriting the mutation. By relying on family history alone, our ability to assess each individual's risk is limited. Recommending such procedures as prophylactic mastectomy for an unaffected individual based on family history alone is problematic. In their article, Levine and Gemignani define the patients who should be considered for genetic counseling. Medical and gynecologic oncologists play a key role in selecting women who should be referred for genetic counseling. Genetic counselors are trained in creating family cancer pedigrees, in identifying possible genetic syndromes, and in discussing the pros and cons of genetic testing. Not all patients who are referred for genetic counseling are recommended for genetic testing. In general, genetic testing is most beneficial when the following two criteria are met: First, the testing is performed on an affected family member, ie, someone who has a personal history of cancer, and second, the pedigree is at least mildly to moderately suggestive of a hereditary breast ovarian cancer syndrome. Communication between the genetic counselor and medical/gynecologic oncologist is crucial. The knowledge that one carries a BRCA1 or BRCA2 mutation not only has an impact on unaffected family members, but can also affect the management of the patient with the newly diagnosed cancer. For example, in a young woman with breast cancer and a substantial family history of premenopausal breast cancer, identification of a BRCA1 mutation may affect the decision to undergo a bilateral mastectomy rather than a unilateral mastectomy. The decision to undergo genetic testing should be made after appropriate counseling about the benefits and limitations of the tests. Certainly, many moderate-risk women will undergo testing and receive inconclusive test results. In addition, a number of women will choose to undergo prophylactic oophorectomy without pursuing genetic testing first. However, providing an accurate assessment of an individual's cancer risk allows the physician to better counsel the patient as to the risks and benefits of prophylactic surgery, as well as the alternatives. Prophylactic Surgery in the Management of High-Risk Women
As reviewed in the paper by Levine and Gemignani, prophylactic mastectomy and prophylactic salpingo- oophorectomy confer substantial protection against the development of breast and ovarian cancer in truly highrisk patients.[5-7] Besides surgical prophylaxis, current options to decrease the risk of ovarian cancer are limited. Although oral contraceptives have been shown to decrease the risk of ovarian cancer in the general population, conflicting reports have emerged regarding the efficacy of oral contraceptives in high-risk women.[ 8,9] Furthermore, one study showed a slight increased risk of breast cancer among BRCA1 mutation carriers under age 30 who use oral contraceptives. Given that there are no effective screening strategies for ovarian cancer, prophylactic salpingo-oophorectomy is a reasonable option for high-risk women who have completed childbearing. An additional benefit of prophylactic salpingo- oophorectomy is a decrease in the risk of breast cancer by approximately 50% among BRCA1 and BRCA2 mutation carriers. The operative procedure should include total removal of the ovaries and fallopian tubes, and the pathologic assessment should include a full histologic examination of the specimens to rule out occult tumors.[ 12,13] The long-term medical effects of surgical menopause and its effect on quality of life have not been adequately studied. A BRCA1 or BRCA2 mutation often is identified after a diagnosis of breast cancer. In high-risk women, prophylactic mastectomy of the contralateral breast has been shown to decrease risk of a second primary. Even in unaffected women with BRCA1 or BRCA2 mutations, prophylactic mastectomy has become an acceptable option for the prevention of breast cancer. Immediate breast reconstruction is often performed. Conclusions
Although there is hope that new chemopreventive and screening strategies will be discovered, prophylactic surgery will likely remain an option for the prevention of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. Women with a suspicious family history should be identified and referred for genetic counseling, and appropriate patients should be offered genetic testing. Women who are found to be mutation carriers should be offered a coordinated plan for the prevention of breast and ovarian cancer. Many of these patients have had firsthand experience with breast or ovarian cancer via a relative who was diagnosed and treated. Although the decision to undergo prophylactic surgery cannot be made lightly, the ability to prevent cancer in these high-risk individuals represents a positive step forward.
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