Management Options After Prophylactic Surgeries in Women With BRCA Mutation
Management Options After Prophylactic Surgeries in Women With BRCA Mutation
Background: Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood.
Methods: The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries.
Results: BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted.
Conclusions: There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.
In families where a strong history of breast and/or ovarian cancer exists, individuals who have not developed cancer may want to ascertain their risk for developing cancer and identify ways to manage this risk. This concern often appropriately leads to genetic counseling and testing, which can identify individuals at increased risk. Mutations in the BRCA1 and BRCA2 genes are responsible for the hereditary breast and ovarian cancer (HBOC) syndrome. The cumulative lifetime risk of breast cancer in women who carry BRCA1 or BRCA2 gene mutations is approximately 60% to 80%, and these cancers often occur at a younger age. The lifetime risk for ovarian cancer in women with BRCA1 mutations is estimated to be 40% to 50% and is slightly lower, 10% to 20%, in women who carry BRCA2 gene mutations.
Although women with BRCA mutations might also be at higher risk for additional malignancies, the absolute risk is small compared to breast and ovarian cancer risk. Original studies suggested a relative risk of two- to fourfold for colon carcinoma in BRCA1 carriers, although this remains debatable. Malignant melanoma was originally reported as at excess relative risk (RR = 2.58, 95% confidence interval [CI] = 1.28 - 5.17; P=.01) in the BRCA2 Linkage Consortium study but not confirmed in a smaller Dutch study; thus, the risk may be higher in specific BRCA2 families. Pancreatic cancer risks for female carriers was also shown to be elevated. In the BRCA2 Linkage Consortium study, estimated cumulative risk for pancreatic cancer by 70 years of age was 1.5% (95% CI = 0.9-2.1). A smaller BRCA2 carrier study in the Dutch population noted a four-fold lifetime risk for pancreatic cancer. For female BRCA1 carriers, the cumulative risk for pancreatic cancer by age 70 was significant (1.26%, 95% CI = 0.92-1.72).
Since the identification of the BRCA genes,a number of advisory bodies and clinicians have published guidelines and review articles delineating clinical management options for individuals with BRCA mutations. Much of the early literature called for consideration of increased cancer surveillance, chemoprevention, and prophylactic surgeries despite the fact that, initially, efficacy of these modalities was unknown. Emerging literature demonstrates the efficacy of many but not all of these primary and secondary prevention and management strategies.
Background: Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood.
Methods: The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries.
Results: BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted.
Conclusions: There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.
In families where a strong history of breast and/or ovarian cancer exists, individuals who have not developed cancer may want to ascertain their risk for developing cancer and identify ways to manage this risk. This concern often appropriately leads to genetic counseling and testing, which can identify individuals at increased risk. Mutations in the BRCA1 and BRCA2 genes are responsible for the hereditary breast and ovarian cancer (HBOC) syndrome. The cumulative lifetime risk of breast cancer in women who carry BRCA1 or BRCA2 gene mutations is approximately 60% to 80%, and these cancers often occur at a younger age. The lifetime risk for ovarian cancer in women with BRCA1 mutations is estimated to be 40% to 50% and is slightly lower, 10% to 20%, in women who carry BRCA2 gene mutations.
Although women with BRCA mutations might also be at higher risk for additional malignancies, the absolute risk is small compared to breast and ovarian cancer risk. Original studies suggested a relative risk of two- to fourfold for colon carcinoma in BRCA1 carriers, although this remains debatable. Malignant melanoma was originally reported as at excess relative risk (RR = 2.58, 95% confidence interval [CI] = 1.28 - 5.17; P=.01) in the BRCA2 Linkage Consortium study but not confirmed in a smaller Dutch study; thus, the risk may be higher in specific BRCA2 families. Pancreatic cancer risks for female carriers was also shown to be elevated. In the BRCA2 Linkage Consortium study, estimated cumulative risk for pancreatic cancer by 70 years of age was 1.5% (95% CI = 0.9-2.1). A smaller BRCA2 carrier study in the Dutch population noted a four-fold lifetime risk for pancreatic cancer. For female BRCA1 carriers, the cumulative risk for pancreatic cancer by age 70 was significant (1.26%, 95% CI = 0.92-1.72).
Since the identification of the BRCA genes,a number of advisory bodies and clinicians have published guidelines and review articles delineating clinical management options for individuals with BRCA mutations. Much of the early literature called for consideration of increased cancer surveillance, chemoprevention, and prophylactic surgeries despite the fact that, initially, efficacy of these modalities was unknown. Emerging literature demonstrates the efficacy of many but not all of these primary and secondary prevention and management strategies.
Source...