Article

Clinical and Pathological Features of Ovarian Cancer in Women with Germ-Line Mutations of BRCA1

Creighton University, Omaha, Nebraska, United States
New England Journal of Medicine (Impact Factor: 55.87). 12/1996; 335(19):1413-6. DOI: 10.1056/NEJM199611073351901
Source: PubMed

ABSTRACT

We tested the hypothesis that ovarian cancers associated with germ-line mutations of BRCA1 have distinct clinical and pathological features as compared with sporadic ovarian cancers.
We reviewed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-line mutations of BRCA1. Survival among patients with advanced-stage cancer and such mutations was compared with that in control patients matched stage, grade, and histologic subtype of the tumors. A combination of single-strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice-donor and splice-acceptor regions of BRCA1 for mutations in pathological specimens. Alternatively, some patients were known to be obligate carriers of the mutant BRCA1 gene because of their parental relationships with documented mutant-gene carriers.
We identified 53 patients with germ-line mutations of BRCA1. The average age at diagnosis was 48 years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, and 3 were of low malignant potential. In 38 patients, the tumors were of stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As of June 1996, with a median follow-up among survivors of 71 months from diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the disease, 4 were alive with the disease, and 2 had died of other diseases. Actuarial median survival for the 43 patients with and advanced-stage disease was 77 months, as compared with 29 months for the matched controls (P<0.001).
As compared with sporadic ovarian cancers, cancers associated with BRCA1 mutation appear to have a significantly more favorable clinical course.

0 Followers
 · 
2 Reads
  • Source
    • "Literature indicates women with an early-onset BC with family history have a higher frequency of BRCA1 and BRCA2 compared to women without a family history[23,24]. Accumulating evidence has shown that different tumor All BC BC (breast cancer) with Severity Information No severity informationcharacteristics were identified in patients with the BRCA1 mutation – less so in patients with the BRCA2 mutation -in comparison to patients without the mutation252627282930. Survival advantage for BC cases with a BRCA1 mutation has been reported[31,32], whereas another study found poor survival when the patient's had BRCA1 mutation[33]. There is discrepancy in the associations between family history and BC prognosis reported to date. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A family history (FH) of breast cancer (BC) is known to increase an individual's risk of disease onset. However, its role in disease severity and mortality is less clear. We aimed to ascertain associations between FH of BC, severity and BC-specific mortality in a hospital-based cohort of 5354 women with prospective information on FH. We included women diagnosed at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2012 (n = 5354). BC severity was defined and categorized as good, moderate, and poor prognosis. Data on BC-specific mortality was obtained from the National Cancer Registry and medical records. Associations between FH and disease severity or BC-specific mortality were evaluated using proportional odds models and Cox proportional hazard regression models, respectively. Available data allowed adjustment for potential confounders (e.g., treatment, socioeconomic status, and ethnicity). FH of any degree was not associated with disease severity at time of diagnosis (adjusted proportional OR: 1.00 [95% CI: 0.85 to 1.17]), which remained true also after stratification by period of diagnosis. FH of BC was not associated with BC-mortality HR: 0.99 (95% CI: 0.93 to 1.05). We did not find evidence to support an association between FH of BC and severity and BC-specific mortality. Our results indicate that clinical management should not differ between women with and without FH, when the underlying mutation is unknown.
    Full-text · Article · Jan 2016 · Cancer Medicine
  • Source
    • "Our findings have important clinical implications. In both breast and ovarian cancers, patients with BRCA mutations are known to have a better clinical outcome [2] [3]. This has been presumed to be due to increased sensitivity to chemotherapy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133(+) ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition-mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.
    Full-text · Article · Apr 2014 · Neoplasia (New York, N.Y.)
  • Source
    • "Our findings have important clinical implications. In both breast and ovarian cancers, patients with BRCA mutations are known to have a better clinical outcome [2] [3]. This has been presumed to be due to increased sensitivity to chemotherapy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.
    Preview · Article · Jan 2014
Show more