I. Characteristics of familial hereditary ovarian cancer Epithelial ovarian cancer is the tumor with the highest mortality rate among gynecological malignancies. Its incidence rate has been gradually increasing in recent years. The latest statistics from the American Cancer Society predict that the number of new cases of ovarian cancer in the United States in 2010 will be about 21,880 and the number of deaths will be about 13,850. The latest statistics released by the Shanghai CDC in China for 2007 show that ovarian cancer has entered the top 10 of female malignant tumor incidence for the first time, with an incidence rate of 5.63 per 100,000 and a mortality rate of 2.24 per 100,000. ovarian cancer is mostly advanced, with heavy disease and poor prognosis, and has become a serious killer of women’s health. After years of research, oncologists have found that ovarian cancer is not completely unpredictable, unpreventable and cannot be intervened early. In addition to sporadic ovarian cancer, a family history of Hereditary Breast and Ovarian Cancer Syndrome (HBOC) has gradually been unveiled. Studies have shown that approximately 5% of breast cancer patients and 10% of ovarian cancer patients present with familial HBOC syndrome. These patients present with an early age of onset, a predominantly plasmacytic papillary cystic adenocarcinoma type of pathology, and a better prognosis. The rate of mutations in the tumor suppressor genes BRCA1 and BRCA2 and the risk of developing cancer were significantly increased compared to disseminated cases. Before discussing how to diagnose these high-risk patients and how to prevent treatment of ovarian cancer in these high-risk patients, we need to understand the BRCA1 and BRCA2 genes, which stands for Breast Cancer Susceptibility Gene 1, a tumor suppressor gene closely associated with the development of familially inherited ovarian cancer. BRCA1 is an oncogene that is strongly associated with the development of ovarian cancer in families. Epidemiological studies have shown that women without BRCA mutations have a lifetime risk of ovarian cancer of 1-2%, while women with BRCA1 mutations have a lifetime risk of 21-51% and women with BRCA2 mutations have a lifetime risk of 11-17%. Therefore, it is necessary to test for the BRCA gene in high-risk groups. How to screen and diagnose familial hereditary ovarian cancer From the health economics point of view, there are no studies to support screening for ovarian cancer in the general population. The National Comprehensive Cancer Network (NCCN) states that routine screening is not recommended, but for high-risk patients, such as those with a family history of ovarian or breast cancer, or those with BRCA mutations, pelvic examination, transvaginal ultrasound and serum cancer antigen (CA125) testing are recommended every 6 months starting at age 35. CA125 test. The diagnosis of familial hereditary breast/ovarian cancer syndrome begins with a family history, which usually involves mapping a family tree of the patient’s family. These families have close relatives with breast, ovarian, or other related cancers; or premenopausal breast cancer; or the patient has multiple related tumors at the same time, such as breast or ovarian cancer; or has male breast cancer; or is of German-Jewish ancestry. These high-risk family members should be screened. The next step is genetic testing of blood specimens, such as BRCA1 and BRCA2, and a positive result for one of these tests can lead to a diagnosis of familial hereditary breast/ovarian cancer syndrome. Other family members may also be tested to determine if they are carriers of the mutation. A negative test result does not completely rule out the diagnosis because current genetic testing techniques cannot detect all mutations or other associated genes. Genetic counseling and genetic testing for familial hereditary breast/ovarian cancer syndrome is currently available at foreign medical institutions such as M.D. Anderson Cancer Center in the U.S., but the cost is high. Qualified companies in China have also conducted this test, which can detect other common mutation gene types in addition to BRCA1/2. Patients can come to the clinic to request this test if they need it. Cibula et al. analyzed several cohort and case-control studies showing that oral contraceptives significantly reduced the occurrence of ovarian cancer, and the protective effect increased with the duration of use, reducing the risk of ovarian cancer by 20% after 5 years of use. This protective effect is independent of the presence of BRCA1 and BRCA2 mutations, and thus can be used as chemoprevention in young BRCA mutation carriers. Oral contraceptives also reduce the risk of endometrial cancer by 50%, but an increased risk of breast and cervical cancer has been found in long-term users. 2. For patients with familial hereditary breast/ovarian cancer syndrome who have completed their reproductive function, prophylactic bilateral oophorectomy and salpingo-oophorectomy is performed, but this measure cannot prevent the occurrence of peritoneal cancer. How to treat patients with familial hereditary ovarian cancer 1. Chemotherapy Platinum-based chemotherapeutic drugs cause impaired DNA replication by cross-linking to DNA, while BRCA1 and BRCA2 are involved in the DNA repair process. In vitro studies have shown that cells with BRCA mutations have increased sensitivity to cisplatin and carboplatin. Clinical studies have shown that epithelial ovarian cancers with BRCA mutations have a higher response rate to first-line platinum-based chemotherapy than the non-BRCA mutation group. In clinical studies, gynecologic oncologists have found that BRCA mutated patients are highly sensitive to platinum but relatively insensitive to paclitaxel, thus suggesting that first-line chemotherapy for epithelial ovarian cancer patients with BRCA mutations need not be supplemented with paclitaxel. In contrast, for patients with recurrent ovarian cancer, the progression-free survival and overall survival of platinum plus paclitaxel combination chemotherapy are higher than those of platinum alone, and the mechanism study may be related to the re-expression of BRCA subpotent alleles. 2. poly (ADP-Ribose) polymerase (PARP) inhibitors DNA repair defects due to inherited BRCA1 gene mutations provide another option for treatment, namely PARP inhibitors. PARP is involved in the cellular signaling of single-stranded DNA breaks and in the repair process of DNA. inhibition of PARP leads to physiological single-stranded DNA breaks The inhibition of PARP leads to the accumulation of physiological single-stranded DNA breaks, which ultimately result in double-stranded breaks during DNA replication. Due to the abnormal homologous repair pathway of double-strand breaks in BRCA-deficient cells, experimental studies have shown increased chromosomal instability, cell cycle arrest and apoptosis in BRCA-deficient cells compared to wild type. Preliminary results from phase I and phase II clinical trials of PARP inhibitors in recurrent ovarian cancer with BRCA mutations are encouraging.Fong reported in the New England Journal that 16 patients with BRCA-mutated ovarian cancer were treated with PARP inhibitors, most of whom were platinum-resistant. Audeh et al. reported that the PARP inhibitor Olaparib (AZD2281) resulted in a complete or partial remission rate of 25% in 57 patients with BRCA-mutated ovarian cancer (42 of whom had platinum-resistant disease) and a stable disease rate in 32%. patients had stable disease. Moreover, treatment response was not affected by platinum sensitivity. Clinical trials of PARP inhibitors in patients with epithelial ovarian cancer and BRCA-associated breast cancer are currently underway. If further studies of the drug continue to show high efficacy and low toxicity, it is highly likely that the drug will enter randomized controlled trials for first-line treatment of BRCA-associated epithelial ovarian cancer.