Reducing the Risk of Gynecologic Cancer in Hereditary Breast Ovarian Cancer Syndrome Mutation Carriers

Abstract

Hereditary breast ovarian cancer (HBOC) syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in 90 percent of affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives (COCs). Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification of prophylactic surgery and the use of COC to reduce the risk of gynecologic cancer in HBOC syndrome mutation carriers. Summary: Hereditary breast ovarian cancer syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in most affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives. Both riskreducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification for those unfavorable effects.

Genetics of Breast and Ovary Cancers Associated with Hereditary Cancers and their Clinical Management

“…Until recently, the tests were performed primarily in patients with a strong family history of cancer and involved a limited number of genes known to be associated with a high risk of cancer or with specific cancer syndromes. With the advent of affordable sequencing, testing with larger gene panels has become possible [80][81][82]. The risk ratios for BC associated with variants in BRCA-1/2 are quite different (10.6 and 5.9, respectively) and correspond to lifetime risks of 55 and 45%, the cumulative risk of MC at 80 years of age it was 72% (95% Confidence Interval [CI], 65 to 79) for BRCA-1 carriers [81].…”

“…With the advent of affordable sequencing, testing with larger gene panels has become possible [80][81][82]. The risk ratios for BC associated with variants in BRCA-1/2 are quite different (10.6 and 5.9, respectively) and correspond to lifetime risks of 55 and 45%, the cumulative risk of MC at 80 years of age it was 72% (95% Confidence Interval [CI], 65 to 79) for BRCA-1 carriers [81]. Population estimates of breast cancer risk associated with germline pathogenic variants in cancer predisposition genes are critically needed for risk assessment and treatment in women with inherited pathogenic variants.…”

“…Population estimates of breast cancer risk associated with germline pathogenic variants in cancer predisposition genes are critically needed for risk assessment and treatment in women with inherited pathogenic variants. These estimates may inform cancer screening and testing and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes [20,[80][81][82]].…”