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Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 ultra-deep sequencing for the detection of disseminated OC cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with OC (6 non-serous and 14 high grade serous-like (serous)). Ultra-deep duplex sequencing (~3000x) with a panel of common OC genes identified the tumor mutation in 33% of non-serous (all early stage) and in 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in KRAS, PIK3CA, PTEN, PPP2R1A and ARID1A presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without OC, indicating prevalent somatic evolution in all patients. Driver TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with OC, suggesting that TP53 -specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of TP53 mutation burden as a potential OC risk factor.

Background: It has been suggested that the likelihood of survival among women with ovarian cancer could be increased by postdiagnosis statin use. This study examines the potential association between postdiagnosis statin use and cancer-specific mortality among women with ovarian cancer., Methods: This cohort study used SEER-Medicare data on women ≥66 years of age diagnosed with ovarian cancer during 2007 to 2012 who were enrolled in Medicare parts A, B, and D during the year after diagnosis. Statin use was defined as two or more fills for a statin during the year after diagnosis. Ovarian cancer-specific death was assessed starting 1 year after diagnosis. Marginal structural Cox models were used, adjusting for the inverse probability of treatment weighting and censoring weighting. Treatment weights and censoring weights were calculated using logistic regression models with a priori -defined covariates., Results: Among 2,195 women with ovarian cancer, 489 (22%) used statins within 1 year after their diagnosis. Over a mean follow-up of 2.2 years, 796 (36%) women died from ovarian cancer. The adjusted HR for ovarian cancer mortality comparing statin users to nonusers was 0.74 (95% confidence interval, 0.61-0.91)., Conclusions: Findings from this and prior work suggest statin use following a diagnosis with ovarian cancer is associated with a lower risk of cancer death., Impact: Because, in most women, statin administration has limited side effects, a randomized trial of statins among patients with ovarian cancer may be warranted., (©2019 American Association for Cancer Research.)