Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women.

PURPOSE: BRCA gene mutations (BRCAm) have an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. METHODS: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). RESULT: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. CONCLUSION: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. TRIAL REGISTRATION: Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Germline mutations in Black patients with ovarian, fallopian tube and primary peritoneal carcinomas.

OBJECTIVE: Routine genetic testing for ovarian cancer and identification of germline mutations can help improve early detection of cancer as well as guide treatment. Knowledge of genetic counseling and referral rates for genetic testing has been lower for Black patients, compared to White patients. We aimed to describe the demographics and presence of germline mutations in Black individuals with ovarian, fallopian tube or peritoneal carcinoma at two large academic institutions. METHODS: Fifty-one Black patients with invasive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were identified via institutional tissue banks over a 20-year time-period. Germline DNA was sequenced using BROCA, a targeted capture and parallel sequencing assay that identified pathogenic germline mutations in ovarian carcinoma susceptibility genes. RESULTS: Germline mutations in ovarian cancer susceptibility genes were found in 25.5% of women, most commonly BRCA1 and BRCA2. This mutation frequency mirrors those previously described among predominantly White populations. Our data suggests there may be an advantage in survival among those with germline mutations, although this was not statistically significant. CONCLUSIONS: Given similar frequencies of germline mutations between Black and White patients with ovarian cancer, we conclude that there are not major differences in the genetic predisposition to ovarian carcinoma. Equitable access to genomic advancements including germline and tumor sequencing would facilitate equal access to PARP inhibitors, the standard of care for patients with BRCA mutated advanced ovarian cancer.

Incidence of ovarian, peritoneal, and fallopian tube carcinomas in the United States, 1995-2004.

OBJECTIVE: The objective of this analysis was to describe the distribution of pelvic carcinomas in the United States by demographic, pathologic, and clinical features. METHODS: Carcinomas of the ovary (n = 112,541), peritoneum (n = 6,458), and fallopian tube (n = 3,479) were identified through 24 population-based registries in the United States during the period 1995 to 2004. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. RESULTS: The age-adjusted incidence rate for ovarian carcinoma (119.9 per million) was substantially higher than for peritoneal (6.78 per million) or fallopian tube (3.72 per million) carcinomas. White women had the highest rates for all three malignancies. Rates for peritoneal carcinoma were lowest among Black women (2.88 per million) and rates for fallopian tube carcinoma were lowest among Hispanic women (2.45 per million). Serous carcinomas were the most commonly diagnosed histologic type for all anatomic sites. Peritoneal carcinomas were diagnosed at later ages (mean, 67 years) and more advanced stages (85% regional/distant) compared with fallopian tube carcinomas (mean, 64 years; 62% regional/distant) and ovarian carcinomas (mean, 63 years; 76% regional/distant). Incidence for all three pelvic carcinomas was lowest in the South. Time trend analyses between 1973 and 2005 exhibited a significant decline in ovarian carcinoma incidence and rises in the rates of peritoneal and fallopian tube cancers. CONCLUSIONS: Similarities in the incidence patterns for ovarian, peritoneal, and fallopian tube carcinomas support the likelihood of a common molecular pathogenesis.

The incidence of primary fallopian tube cancer in the United States.

OBJECTIVE: The objective of this study was to report the incidence of primary fallopian tube carcinoma (PFTC) in the United States population and to describe associated demographic and clinical factors. METHODS: A total of 3051 PFTC cases diagnosed from 1998 to 2003, reported from population-based cancer registries, were analyzed. Registries contributing data represent 83.1% of the U.S. population. Data are presented by age, race/ethnicity, U.S. census region, stage, histology, grade, and laterality. Trends in incidence over time from 1998 to 2003 are also presented. RESULTS: The incidence rate was 0.41 per 100,000 women from 1998 to 2003. White, non-Hispanic women and women aged 60-79 had the highest incidence rates (p<0.0001). The majority (88%) of PFTCs were adenocarcinomas; serous adenocarcinomas accounted for 44% and endometrioid adenocarcinomas for 19% of adenocarcinoma diagnoses. Essentially half (49.9%) of PFTCs were poorly differentiated; 89% were unilateral at diagnosis. Stage at diagnosis was fairly evenly distributed among localized (36%), regional (30%), and distant (32%). Overall, rates of PFTC remained stable over time. Among women aged 65-69, incidence rates increased significantly by 3.8% per year from 1998 to 2003 (p<0.05). CONCLUSIONS: This report provides characteristics of PFTC using the largest number of cases assembled in one study to date. Although the demographic characteristics of PFTC are similar to those of ovarian cancer, stage at diagnosis and the stable trend observed in PFTC are in contrast to ovarian cancer. Future studies should focus on examining the increasing trend of PFTC among 65- to 69-year-old women.