OBJECTIVE To estimate the incidence of genetic counseling referral for ovarian cancer patients who are at substantial risk for a BRCA1 or BRCA2 mutation. METHODS An analysis was performed of new ovarian cancer patients who were seen at a comprehensive cancer center from January 1, 1999, through December 31, 2007. Patients at substantial (more than 20–25%) risk for a BRCA1 or BRCA2 mutation were identified and records reviewed for referral to genetic counseling. Time to referral was estimated using the Kaplan-Meier method. RESULTS A total of 3,765 epithelial ovarian cancer patients were seen during the 9-year period. On average, 23.8% of patients met substantial-risk criteria for BRCA mutations. In 1999, only 12% of patients at substantial-risk were referred. Referral improved over time with 48% referred in 2007 (P<.001). Newly diagnosed patients were more often referred for genetic counseling than new patients with recurrent disease or those seen as second opinions. African-American women meeting substantial-risk criteria were less likely to be referred than were white or Hispanic women (P=.009). CONCLUSION Although dictated family history was accurate, interpretation of risk for BRCA1 or BRCA2 mutations and subsequent referral to genetic counseling was poor. Although there was significant improvement over time, 50% of substantial-risk patients still were missed. Systematic efforts to identify those ovarian cancer patients at substantial risk for a BRCA1 or BRCA2 are necessary. LEVEL OF EVIDENCE III
Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.
OBJECTIVE-To estimate the incidence of genetic counseling referral for ovarian cancer patients who are at substantial risk for a BRCA1 or BRCA2 mutation.METHODS-An analysis was performed of new ovarian cancer patients who were seen at a comprehensive cancer center from January 1, 1999, through December 31, 2007. Patients at substantial (more than 20-25%) risk for a BRCA1 or BRCA2 mutation were identified and records reviewed for referral to genetic counseling. Time to referral was estimated using the Kaplan-Meier method.RESULTS-A total of 3,765 epithelial ovarian cancer patients were seen during the 9-year period. On average, 23.8% of patients met substantial-risk criteria for BRCA mutations. In 1999, only 12% of patients at substantial-risk were referred. Referral improved over time with 48% referred in 2007 (P<.001). Newly diagnosed patients were more often referred for genetic counseling than new patients with recurrent disease or those seen as second opinions. AfricanAmerican women meeting substantial-risk criteria were less likely to be referred than were white or Hispanic women (P=.009).CONCLUSION-Although dictated family history was accurate, interpretation of risk for BRCA1 or BRCA2 mutations and subsequent referral to genetic counseling was poor. Although there was significant improvement over time, 50% of substantial-risk patients still were missed. Systematic efforts to identify those ovarian cancer patients at substantial risk for a BRCA1 or BRCA2 are necessary. LEVEL OF EVIDENCE-IIIClinical genetic testing for germline mutations in BRCA1 and BRCA2, the genes that account for the majority of hereditary breast and ovarian cancer families, has been available In recent years, it has become clear that there are important reasons to focus genetic testing efforts on the cancer patient. First, directing genetic testing efforts toward cancer patients rather than unaffected individuals is an efficient means to identify the specific deleterious mutation in a family. [16][17][18] Once the specific mutation is identified, unaffected family members can be offered accurate genetic testing just for the known mutation. In this setting, both positive and negative genetic test results are interpretable and informative. Although genetic testing in the past has not had an effect on the treatment of ovarian cancer patients, clinical trials of poly ADP ribose polymerase inhibitors currently are underway specifically for breast and ovarian cancer patients with BRCA1 or BRCA2 mutations, and different therapeutic regimens may be prescribed based on a patient's genetic test results. In addition, BRCA status has prognostic significance for ovarian cancer patients. [19][20][21][22][23] Given the importance of identifying ovarian cancer patients who are highly likely to carry a BRCA1 or BRCA2 mutation, the question remains: "How successful are physicians at identifying these individuals?" The purpose of this study was to estimate the incidence of referral of new ovarian cancer patients who had a substantial (more than 2...
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