Patients with BRCA mutations have superior outcomes after intraperitoneal chemotherapy in optimally resected high grade ovarian cancer.

OBJECTIVES: To compare the outcomes after intraperitoneal (IP) chemotherapy in patients with and without pathogenic BRCA mutations. METHODS: Patients with high grade ovarian cancer who were treated with adjuvant IP chemotherapy in the initial setting between 2005 and 2016 were identified. Outcomes were compared between patients with pathogenic mutations in BRCA (BRCA+) and those who tested negative or were unknown (BRCA-). RESULTS: A total of 100 eligible patients were identified. The median follow-up was 47.0 months (range, 6.6-144.1 months). Of these 100 patients, 77 patients underwent BRCA testing; 25 patients (32%) were BRCA+ (23 germline, 2 somatic). No differences were noted between groups with respect to number of IP cycles, stage, or residual disease after surgery. The median progression-free survival (PFS) was longer in the BRCA+ group; median PFS was not reached in the BRCA+ group compared to 17.3 months in the BRCA- group (HR = 0.38; 95% CI 0.20-0.73, P = 0.003). Median overall survival (OS) was longer in the BRCA+ group at 110.4 months versus 67.1 months (HR = 0.28, 95% CI 0.11-0.73, P = 0.009). CONCLUSIONS: Pathogenic BRCA mutations are more common than expected in optimally resected ovarian cancer patients selected for IP therapy. IP therapy was associated with a dramatic improvement in PFS and OS in BRCA+ patients compared with BRCA- patients. This improvement is greater than has been reported for BRCA+ patients with IV chemotherapy. The magnitude of this benefit suggests that patients with pathogenic mutations in BRCA may benefit from IP therapy.

A Comprehensive Program Enabling Effective Delivery of Regional Genetic Counseling.

OBJECTIVES: The aim of this study was to demonstrate the utility of a comprehensive program involving management-based evidence, telemedicine, and patient navigation to provide genetic counseling services for patients with ovarian and breast cancer across a geographically large health care system. METHODS: We identified all patients with newly diagnosed ovarian and breast cancer in our health care system from January 2013 to December 2015 through the cancer registry. Referral characteristics and testing outcomes were recorded for each year and compared using the χ or Fisher exact test. RESULTS: Because the implementation of this program, the number of new ovarian cancer cases remained constant (109-112 cases/year) but patients referred for genetic counseling increased annually from 37% to 43% to 96% (P < 0.05). The percentage of ovarian cancer patients who underwent genetic testing increased annually from 24% to 27% to 53% (P < 0.05). The number of new breast cancer patients was constant (1543-1638 cases/year). The percentage of patients with triple negative breast cancer referred for genetic counseling rose from 69% in 2013 to 91% in 2015; the percentage of patients who underwent testing increased annually from 59% to 86% (P < 0.05). Of women with breast cancer diagnosed at less than 45 years of age, 78% to 85% were referred for genetic counseling across this period; the percentage of patients who underwent testing increased annually from 66% to 82% (P < 0.05). Patient navigation was initiated and was available to all patients in the system during this period. Telemedicine consults were performed in 118 breast/ovarian patients (6%) during this period. CONCLUSIONS: A comprehensive program may improve access to effective genetic counseling services in patients with ovarian and breast cancer despite geographic barriers.

Genetic Testing for Hereditary Breast Cancer: The Decision to Decline.

Genetic testing is important for comprehensive cancer care. Commercial analysis of the BRCA1/2 genes has been available since 1996, and testing for hereditary breast and ovarian cancer syndrome is well established. The National Comprehensive Cancer Network (NCCN) guidelines identify individuals for whom BRCA1/2 analysis is appropriate and define management recommendations for mutation carriers. Despite recommendations, not all who meet NCCN criteria undergo genetic testing. We assess the frequency that individuals meeting NCCN criteria decline BRCA1/2 analysis, as well as factors that affect the decision-making process. A retrospective chart review was performed from September 2013 through August 2014 of individuals who received genetic counseling at the Levine Cancer Institute. A total of 1082 individuals identified through the retrospective chart review met NCCN criteria for BRCA1/2 analysis. Of these, 267 (24.7%) did not pursue genetic testing. Of the Nontested cohort, 59 (22.1%) were disinterested in testing and 108 (40.4%) were advised to gather additional genetic or medical information about their relatives before testing. The remaining 100 (37.5%) individuals were insured and desired to undergo genetic testing but were prohibited by the expense. Eighty five of these 100 patients were responsible for the total cost of the test, whereas the remaining 15 faced a prohibitive copay expense. Financial concerns are a major deterrent to the pursuit of BRCA1/2 analysis among those who meet NCNN criteria, especially in patients diagnosed with breast or ovarian cancer. These findings highlight the need to address financial concerns for genetic testing in this high-risk population.

Surgical Decision Making in the BRCA-Positive Population: Institutional Experience and Comparison with Recent Literature.

A retrospective study was performed to document the uptake and extent of surgical intervention in patients with a known mutation in the BRCA1/2 genes and associated outcomes. Data were collected retrospectively on BRCA-positive patients with and without cancer at the time of genetic testing. Our findings were compared to those published in the current literature. Of patients with cancer at testing, 61% chose bilateral mastectomies. Of patients without cancer, 54% chose risk-reducing surgery (RRS) including risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), or both. Time to surgery was significantly shorter to RRSO than to RRM. The literature suggests and our data support that acceptance of RRM in the BRCA-positive population has gradually increased over time. Consistently high rates of RRSO uptake and short intervals from time-of-testing to RRSO demonstrate that RRSO is still more acceptable to this population than RRM.