Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma.

OBJECTIVE: Universal genetic testing has become increasingly important in the management of epithelial tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population, given its specific genetic background (French-Canadian ancestry). METHOD: Mainstream genetic testing was implemented in our service in May 2017 and offered to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous and borderline tumours. Data were prospectively collected in a database and retrospectively analyzed. RESULTS: We tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma (HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non-BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total of 63 different variants of unknown significance (VUS) were found, of which 4 were in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only 1 was found in low-grade serous carcinoma. CONCLUSION: In our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%-less than half that reported in the literature. This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy. Mainstream genetic testing was successfully implemented in our service and facilitated access to genetic testing in our patient population.

Treatment of Secondary Vestibulodynia with Conjugated Estrogen Cream: A Pilot, Double-Blind, Randomized Placebo-Controlled Trial.

OBJECTIVE: To assess the efficacy of conjugated equine estrogen cream in reducing dyspareunia associated with secondary provoked vestibulodynia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial that included women with secondary provoked vestibulodynia. Participants were randomly allocated to daily application of conjugated equine estrogen cream on the vulvar vestibule (estrogen group) or daily application of a similar placebo cream (placebo group). All patients were evaluated before and after eight weeks of treatment, using a visual analogue scale for superficial dyspareunia (primary outcome), the McGill Pain Questionnaire for superficial dyspareunia, the Female Sexual Function Index for sexual satisfaction, and vulvoscopy for vestibular erythema. RESULTS: The targeted recruitment for this study was 44 women, but because of funding shortfalls recruitment was limited to 20 women. These 20 participants were randomly assigned to two groups of 10. Improvement of superficial dyspareunia on the visual analogue scale was not significantly different between the two groups (estrogen group: 27% improvement vs. placebo group: 3% improvement, P = 0.29). However, the use of conjugated equine estrogen cream was associated with a significant post-treatment improvement in superficial dyspareunia and in all three secondary outcomes (P < 0.05), whereas this was not the case with the use of placebo. CONCLUSION: Daily application of conjugated equine estrogen cream to the vulvar vestibule could potentially reduce superficial dyspareunia in women with secondary provoked vestibulodynia, but a randomized trial with adequate statistical power will be required to demonstrate this.