Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer

Abstract

Abstract. Risk-reducing surgery (RRS) is defined as a prophylactic approach with removal of organs at high risk of developing cancer, which is performed in cases without lesions or absence of clinically significant lesions. Hereditary gynecological cancers for which RRS is performed include hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. For HBOC, RRS in the United States (US) is recommended for women with mutations in the breast cancer susceptibility (BRCA)1 and BRCA2 genes and bilateral salpingo-oophorectomy (BSO) is generally performed. This procedure may reduce the risk of breast, ovarian, Fallopian tube and primary peritoneal cancer, although ovarian deficiency symptoms occur postoperatively. For Lynch syndrome, RRS in the US is considered for postmenopausal women or for women who do not desire to bear children and BSO and hysterectomy are usually performed. This approach may reduce the risk of endometrial and ovarian cancer, although ovarian deficiency symptoms also occur. For RRS, there are several issues that must be addressed to reduce the risk of cancer development in patients with HBOC or Lynch syndrome. To the best of our knowledge, this is the first review to discuss RRS with a focus on hereditary gynecological cancer. IntroductionHereditary gynecological cancers include ovarian cancer associated with hereditary breast and ovarian cancer (HBOC); endometrial and ovarian cancer associated with Lynch syndrome; endometrial, cervical and ovarian cancer associated with Peutz-Jeghers syndrome; and ovarian cancer associated with Cowden disease. HBOC is an autosomal dominant hereditary disease that may cause breast, ovarian, Fallopian tube and peritoneal cancer.Mutations of the breast cancer susceptibility (BRCA)1 and BRCA2 genes have been identified in ~8-13% of patients with ovarian cancer (1,2). By the age of 70 years, the estimated risks of developing ovarian cancer are 35-60 and 10-27% in BRCA1 and BRCA2 mutation carriers, respectively (2). The mean ages at diagnosis of ovarian cancer are 54, 62 and 63 years for BRCA1 and BRCA2 mutation carriers and non-carriers, respectively, indicating that BRCA1 mutation carriers are more likely to be affected by ovarian cancer at a younger age (3). Clinicopathologically, the majority of ovarian cancers that are BRCA1/2 mutation-positive are of serous histology and are poorly differentiated (grade 3) stage III-IV tumors, according to the International Federation of Gynecology and Obstetrics (FIGO) staging criteria, as defined in 1988 (4,5). In BRCA1/2 mutation-positive and -negative cases, the rates of serous adenocarcinoma are 63-86 and 57-58%, those of poorly differentiated tumors 68-87 and 48-58% and those of stage III-IV tumors 72-88 and 62-70%, respectively.Lynch syndrome, also referred to as hereditary non-polyposis colorectal cancer, is an autosomal dominant hereditary disease that may lead to colorectal, endometrial, gastric and ovarian cancer. Lynch syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes, which include mu...

Cost-effectiveness Analysis of Genotype-Specific Surveillance and Preventive Strategies for Gynecologic Cancers Among Women With Lynch Syndrome

“…7 Risk-reducing surgical treatment (RRS) involving total hysterectomy with bilateral salpingo-oophorectomy (hyst-BSO) is recommended as an option for individuals with LS after the completion of childbearing. 5 , 8 However, the optimal timing of hyst-BSO is uncertain given the association of surgical menopause with decreased quality of life.…”

Interventions to reduce the risk of ovarian and fallopian tube cancer: A European Menopause and Andropause Society Position Statement

“…Women with hereditary nonpolyposis colon cancer (Lynch syndrome) also have an increased risk of endometrial cancer and (to a lesser extent) ovarian cancer. Women with Lynch syndrome have a lifetime risk of ovarian cancer of about 10% and they represent up to 1% of all EOCs [51,52].…”

Oncofertility in Gynecologic Malignant Tumors

“…HBOC is an autosomal dominant hereditary disease caused by germline mutation of breast cancer susceptibility (BRCA) 1 and BRCA2 gene. The estimated risks of developing ovarian cancer by the age of 70 years are 35% -60% and 10% -27% in BRCA1 and BRCA2 mutation carriers, respectively [5]. Lynch syndrome is also an autosomal dominant hereditary disease and it is caused by germline mutation of DNA mismatch repair (MMR) genes, which include mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), MSH6 and postmeiotic segregation increased 2 (PMS2) [6].…”

“…Lynch syndrome is also an autosomal dominant hereditary disease and it is caused by germline mutation of DNA mismatch repair (MMR) genes, which include mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), MSH6 and postmeiotic segregation increased 2 (PMS2) [6]. For patients of Lynch syndrome, the estimated risk of endometrial and ovarian cancer at the age of 70 years are about 60% and 12%, respectively [5]. Because effectiveness of screening methods against these hereditary gynecologic cancer have not been proved, risk-reducing surgery, which is a prophylactic surgery to remove ovary, fallopian tube or uterus might be performed before the onset of cancer.…”