ROMA guided conservative management for women diagnosed with an ovarian cyst or pelvic mass

Objectives: PTEN mutations are frequently observed in endometrioid uterine cancer and lead to hyperactivation of the PI3K/Akt pathway. However, the role of BRCA1 and 2 mutations, leading to homologous recombination deficiency, is not known in this disease. We sought to determine the frequency and clinical significance of BRCA mutations in patients with uterine cancer and PTEN mutations. Methods:We assessed PTEN, BRCA1, and BRCA2mutation status for 248 uterine tumor samples using level 3 data fromThe Cancer GenomeAtlas (TCGA). We performed mutation analysis for PTEN, BRCA1, and BRCA2 for an additional 251 samples from TCGA using ANNOVAR. A total of 499 patientswere included in the analysis. Clinical data, including stage, tumor histology, and overall survival, were also extracted. Fisher's exact tests were used to identify the association betweenmutation status and histologic subtype. Kaplan–Meier plots were constructed to demonstrate survival differences between groups. Results: Among the samples analyzed, 335 (67%) had endometrioid histology, 76 (15%) had serous histology, 18 (44%) had mixed histology, and histology was unknown in the remainder of cases. Of the patients with endometrioid histology, 260 (78%) had a PTEN mutation, 23 (7%) had both BRCA1 and 2 mutations, 4 (1%) had mutations in BRCA1 only, and 25 (8%) hadmutations in BRCA2 only. A total of 52/335 patients (16%) had mutations in either BRCA1 or 2; 18/52 (35%) of these had stage II or above disease and the remainder had stage I disease. No survival advantage was detected in patients with BRCA1 mutations over wildtype BRCA1, independent of PTEN mutation status (P=0.16 and 0.19, respectively). Patients with both PTEN and BRCA2 mutations had improved overall survival compared to patients with wild-type PTEN and BRCA2 (P=0.03). A singlemutation in BRCA1, BRCA2, or PTEN did not confer a significant survival advantage compared towild-type (P=0.15). Conclusions: BRCA1 and 2 mutations are prevalent in patients with endometrioid uterine cancer, and PTEN/BRCA2 double mutations are associated with prolonged patient survival. These findings may have significant clinical and treatment implications.