br Results br Of the consented patients with a pre
Of the 1549 consented patients with a pre-operative diagnosis of EC or CAH, 372 were excluded either due to lack of blood samples (n = 205), non-endometrial primary cancer (n = 40), or CAH based on final pathology (n = 127). In addition, three samples were not submit-ted for sequencing due to failed quality control following library prepa-ration, and four patients were excluded due to a high degree of relatedness to another individual identified in the bioinformatics quality control process. Among the remaining 1170 patients, there were 849 (72.6%) with type I EC and 321 (27.4%) with type II EC, of which 135 were uterine serous cancers (11.5%). Demographic and clinical charac-teristics are summarized in Table 1. Among the 321 patients with type
Summary of demographic and clinical characteristics.
Characteristic All Type I EC Type II EC
Abbreviations: BMI, body mass index; EC, endometrial cancer; FIGO, International Feder-ation of Gynecology and Obstetrics; n/a, not applicable; SD, standard deviation. a Includes endometrioid/mucinous histology.
Demographic and clinical characteristics were compared between cancer predisposition gene PR-619 carriers and non-carriers in Table 2. Mean age at surgery was significantly lower among patients with cancer predisposition gene mutations (mean (SD), 60.1 (9.7) vs. 63.8 (10.2); p = 0.01). However, this difference is likely explained by the younger age at diagnosis among patients with MMR/Lynch syn-drome gene mutations (mean (SD), 56.6 (7.2) years). There was no sta-tistically significant age difference between cancer predisposition gene mutation carriers and wildtype patients when the 17 patients with LS gene mutations were excluded (61.8 (10.3) vs. 63.8 (10.2), p = 0.24). Overall, 9% (9/100) of pre- or peri-menopausal women had a cancer predisposition gene mutation compared with 4.1% (43/1058) of post-menopausal women (p = 0.038). For type I EC, mean BMI was signifi-cantly lower in cancer predisposition gene mutation carriers compared to non-carriers (mean (SD), 31.3 (7.7) vs. 36.4 (9.5); p = 0.002). Stage at diagnosis was not significantly different between patients with and without cancer predisposition gene mutations.
The incidence of germline BRCA1/2 mutations was low in type I EC, type II EC, and USC with rates of 0.47% (95% CI, 0.13–1.20%), 0.93% (95% CI, 0.19–2.71%), and 0.74% (95% CI, 0.02–4.06%), respectively. The rate of BRCA1 mutations was higher among patients with type II com-pared to type I EC, though the difference was not statistically significant. BRCA1 mutations were found in only 0.12% (1/852) of type I EC (95% CI 0–0.65%) compared to 0.93% (3/321) of type II EC (95% CI 0.19–2.71%) (p = 0.07) (Fig. 1 and Table 2). Of the three cases of type II EC, one was grade 3 endometrioid, one carcinosarcoma, and one USC. Family history of breast cancer was present in all four BRCA1 mutation carriers, but there was no family history of EC or ovarian cancer. One BRCA1 mu-tation carrier also had a personal history of breast cancer. All BRCA1 mu-tation carriers were post-menopausal at EC diagnosis. BRCA2 mutations were identified in three patients with type I EC (0.35%), including two diagnosed with grade 2 endometrioid and one diagnosed with grade 1 endometrioid. No type II EC cases had BRCA2 mutations. None of the BRCA2 mutation carriers had a personal history of breast cancer or a family history of breast, ovarian, or endometrial cancer. In addition, none of the patients with USC and a history of breast cancer and/or ta-moxifen exposure were found to have BRCA1/2 mutations.
Fig. 1. Rates of cancer predisposition gene mutations in specific EC subtypes. * Does not include p.Ile157Thr. ^ Does not include variants in PMS2 pseudogene region or c.736_741del6ins11.
# All USC cases and mutations are included in the Type II frequencies.
Comparison of demographic and clinical characteristics between cancer predisposition gene mutation carriers and non-carriers.
Type I EC
Type II EC
Cancer pre-disposition Non-carriers Pa
Cancer pre-disposition Non-carriers Pa Cancer pre-disposition Non-carriers Pa
Abbreviations: BMI, body mass index; EC, endometrial cancer; FIGO, International Federation of Gynecology and Obstetrics; n/a, not applicable; SD, standard deviation.
a Comparisons between the mutation carriers and non-carriers were evaluated using the two-sample t-test for age and BMI, the chi-square test for grade, and the Fisher's exact test for Caucasian race, stage, and histology. b Includes endometrioid/mucinous histology.