Abstract
Simple SummaryThe BRCA genetic test and HRD (homologous recombination deficiency) test are used as a companion diagnosis before starting PARP (poly ADP-ribose polymerase) inhibitor treatment. In clinical practice, gynecologists treating ovarian cancer are faced with decisions such as whether to recommend germline BRCA (gBRCA) test to all ovarian cancer patients and whether to do the gBRCA test first or HRD test first. Regarding the judgment result of the HRD test, the cutoff value differs depending on the clinical trial, and the prevalence of gBRCA pathogenic variant rate is different in each histological type and country. RRSO (risk reducing salpingo-oophorectomy) may have possibly reduced the risk of breast cancer for BRCA2 pathogenic variant carriers but not for BRCA1 carriers.In the field of gynecology, the approval of the PARP inhibitors (PARPi) has been changing the treatment of ovarian cancer patients. The BRCA genetic test and the HRD test are being used as a companion diagnosis before starting PARPi treatment. BRACAnalysis CDx® and Myriad myChoice® HRD test are widely used as a BRCA genetic test and HRD test, respectively. In addition, FoundationOne®CDx is sometimes used as a tumor BRCA test and HRD test. In clinical practice, gynecologists treating ovarian cancer are faced with making decisions such as whether to recommend the gBRCA test to all ovarian cancer patients, whether to perform the gBRCA test first or HRD test first, and so on. Regarding the judgment result of the HRD test, the cutoff value differs depending on the clinical trial, and the prevalence of gBRCA pathogenic variant rate is different in each histological type and country. A prospective cohort study showed that RRSO reduced all-cause mortality in both pre- and postmenopausal women; however, RRSO significantly reduced the risk of breast cancer for BRCA2 pathogenic variant carriers, but not for BRCA1 pathogenic variant carriers. Moreover, salpingectomy alone is said to not decrease the risk of developing ovarian or breast cancer, so further discussion is evidently required. We discuss the current situation and problems in doing BRCA genetic test and RRSO in this review article.
Highlights
Hereditary breast and ovarian cancer (HBOC) caused by germline BRCA1/2 gene pathogenic variant is predicted to be responsible for about 5% of all breast cancers and 15% of all ovarian cancers [1,2]
The BRCA genetic test and homologous recombination deficiency (HRD) test are currently used as a companion diagnosis before starting Poly (ADP-ribose) polymerase inhibitors (PARPi) treatment
The indication of olaparib was expanded to include its combination with bevacizumab for first-line maintenance treatment of patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA variant, and/or genomic instability based on the results of PAOLA-1 trial [8]
Summary
Hereditary breast and ovarian cancer (HBOC) caused by germline BRCA1/2 gene pathogenic variant (gBRCAm) is predicted to be responsible for about 5% of all breast cancers and 15% of all ovarian cancers [1,2]. Based on the results of SOLO 1 (phase III) [7], olaparib was approved for the maintenance treatment of patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. The indication of olaparib was expanded to include its combination with bevacizumab for first-line maintenance treatment of patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA variant, and/or genomic instability based on the results of PAOLA-1 trial [8]. HRD is defined by either a deleterious or suspected deleterious BRCA variant, or genomic instability in patients with a disease progression greater than six months after their response to the last platinum-based chemotherapy
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