Christine Garcia

Comparison of risk management strategies between women testing positive for a BRCA variant of unknown significance and women with known BRCA deleterious mutations

Purpose:The aim of this article is to describe cancer risk–reducing behaviors of women with BRCA variants of unknown significance.Methods:A retrospective chart review from 1995 to 2012 identified women with BRCA mutations in a northern California community system. Exclusion criteria included loss of membership/death within 1 year of testing, prior ovarian cancer, or bilateral salpingo-oophorectomy. Primary outcomes were rate of risk-reducing mastectomy and risk-reducing salpingo-oophorectomy.Results:The mean age of the 69 variant of unknown significance carriers was 50 vs. 47 years for the 305 women with a deleterious mutation. Women with a variant of unknown significance were followed for a median of 69 months. Among women with a variant of unknown significance, 30% underwent risk-reducing salpingo-oophorectomy and 11% underwent risk-reducing mastectomy, as compared with 74 and 44%, respectively, for women with a deleterious mutation. Women with a deleterious mutation were more likely to undergo surveillance in the first year after testing. The odds ratios are as follows: 2.1 for mammogram, 6.0 for magnetic resonance imaging, 7.7 for Ca-125, and 5.0 for transvaginal ultrasound. Fifty-six percent of women with a variant of unknown significance were reclassified after a median of 39 months, longer than the median time to risk-reducing salpingo-oophorectomy (18.6 months) or risk-reducing mastectomy (20.1 months).Conclusion:Uptake of risk-reducing strategies among women with a variant of unknown significance is lower than among women with a deleterious mutation. Given the prognostic uncertainty and high rate of reclassification for women with a variant of unknown significance, individualizing counseling and directing efforts toward surveillance, chemoprevention, or salpingectomy are recommended.Genet Med 16 12, 896–902.

Venous thromboembolism following minimally invasive surgery among women with endometrial cancer

OBJECTIVE To determine the rate of venous thromboembolism (VTE) among women undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS Women undergoing robotic or laparoscopic hysterectomy for endometrial carcinoma or complex hyperplasia with atypia were identified between January 2009 and 2014 in a community based health care system. Patient data including age, race, cancer stage, grade, procedure type, length of hospital stay, use of prophylaxis, and diagnosis of VTE were collected retrospectively. The primary outcome was the rate of VTE within 30days following surgery. Fischers exact tests were performed to evaluate factors associated with VTE. RESULTS During the study period, 1433 patients underwent MIS for endometrial cancer, with 20 excluded due to known thrombophilia, VTE history, or long-term anticoagulation. A total of 1413 patients were included (739 robotic and 674 laparoscopic cases). All women received mechanical prophylaxis per hospital policy and 61% had additional pharmacologic prophylaxis. The rate of VTE was 0.35% (5/1413), which did not differ among those who received pharmacologic compared to mechanical prophylaxis (0.23% [2/865] versus 0.55% [3/548] respectively, p=0.38). No factors were associated with increased risk of VTE due to the low event rate. CONCLUSION VTE in patients undergoing MIS for endometrial cancer was very low irrespective of the mode of prophylaxis received in this large cohort. National guidelines for VTE prophylaxis need to differentiate the low risk associated with MIS surgery from the risk associated with laparotomy for endometrial cancer. We recommend mechanical prophylaxis is sufficient for these women undergoing MIS.

Prospective screening with the validated Opioid Risk Tool demonstrates gynecologic oncology patients are at low risk for opioid misuse

OBJECTIVE To characterize risk for opioid misuse among gynecologic oncology patients. METHODS The Opioid Risk Tool (ORT), a validated screen for opioid misuse risk, was administered to a convenience sample of patients with gynecologic cancer receiving opioid prescriptions in gynecologic oncology or palliative care clinics from January 2012-June 2016. Demographic and clinical information was abstracted on chart review. The primary outcome was ORT risk level (low vs. moderate or high). Chi-square tests were performed for categorical variables. RESULTS A total of 118 women were screened. Most women were Caucasian (79%) with a median age of 57years. Ovarian cancer patients comprised 46% of the cohort with fewer endometrial (25%), cervical (23%), vulvar (4%), and vaginal (2%) cancer patients. The median ORT score was 1.0 (range, 0-10) out of a possible 26. Overall, 87% of patients were categorized as low-risk for opioid misuse, 7% as moderate-risk, and 6% as high-risk. Patients who were at moderate or high-risk of opioid misuse were significantly younger (47 vs. 58years, p=0.02), more likely to have cervical cancer (p=0.02), be smokers (p=0.01) and be uninsured or on Medicare (p=0.03). CONCLUSIONS Most gynecologic oncology patients in our cohort were low-risk for opioid misuse (87%). Cervical cancer patients were more likely to be moderate to high-risk for misuse. Future screening efforts for opioid misuse may have the highest utility in this subset of patients.

A SEER-Medicare analysis of the impact of metformin on overall survival in ovarian cancer

OBJECTIVE Determine whether metformin use is associated with improved survival in patients with ovarian, fallopian tube or primary peritoneal cancer. METHODS All patients with a diagnosis of first epithelial ovarian cancer from 2007 to 2011 in the combined SEER-Medicare database were identified from the SEER registry primary site codes. Comorbidities, procedures and cancer treatment ICD-9 and HCPCS codes were used to search the Medicare claims files. Medication use was determined with National Drug Codes using the Medicare Part D event files. The primary outcome, overall survival, was assessed between metformin users and non-users using a Cox Proportional Hazards survival model. To control for confounding, metformin users were matched to non-metformin users using propensity scores. Effect of dosage on survival was assessed using discrete time survival analysis with pooled logistic regression (PLR). RESULTS There were 2291 cases that met our inclusion criteria. Of these, 180 (7.9%) had been on metformin. The median age was 73years, with the majority of the population being White (83.5%) and treated with primary surgery (74.1%). Metformin use was not associated with overall survival in the entire cohort (HR 0.96, 95% CI 0.75-1.23) or in the matched sample cohort (HR 0.88, 95% CI 0.66-1.17). However, exploratory regression with time-varying coefficients suggests a protective metformin effect for women alive after 30months follow-up (HR=0.37, 95% 0.16-0.87). CONCLUSION No statistically significant association was observed between metformin use and overall survival in a matched cohort of 360 ovarian cancer patients. However, exploratory modeling suggests metformin use may be protective in a certain subgroup of patients.

Cutting costs and standardizing care: Once-per-cycle complete blood count monitoring may be safe for patients undergoing platinum-based chemotherapy

The aim of this study was to evaluate whether frequency of complete blood count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital admissions or rates of neutropenic fever.