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Background: The majority of women with endometrial cancer (EC) present at an early stage with an associated 5-year survival rate of >90%. High rates of early detection are attributed to warning symptoms; however, the prevalence of such symptoms has not been well defined. Methods: A case-control study was conducted assessing the prevalence of symptoms in EC patients at a large cancer center compared with healthy controls. Controls included patients seen for an annual gynecologic care visit (AV) or for a gynecological problem-based visit (PV). A self-administered questionnaire was given to all participants addressing EC-associated symptoms, at the time of initial clinic visit. Odds ratios (ORs) were used to compare prevalence of symptoms between EC cases and controls. Logistic regression was used to determine the impact of menopausal status and obesity on symptom prevalence. Results: The cases ( n = 75) were significantly older than the AV ( n = 203) and PV ( n = 151) controls (59.7 vs. 49.8 vs. 51.0 years, p < 0.01), had a higher body mass index (35.5 vs. 29.4 vs. 30.9 kg/m2, p < 0.01), and were more likely to be postmenopausal (76% vs. 53.7% vs. 52.0%, p < 0.01). The cases were more likely to report postmenopausal bleeding (OR = 32.99 and 5.83, p < 0.01) and abnormal vaginal discharge (OR = 8.8 and 3.3, p < 0.01) compared with the AV and PV groups. Overall, 55.4% of cases reported abnormal vaginal discharge. Conclusions: Symptoms of both postmenopausal bleeding and abnormal vaginal discharge were significantly higher in EC compared with controls. The presence of such symptoms should raise concern for malignant disease and prompt immediate gynecological evaluation. [ABSTRACT FROM AUTHOR]

The genotype-phenotype correlations of the specific BRCA1 and BRCA2 mutations in multi-ethnic populations in USA have not yet been fully investigated. This study was designed to evaluate the effects of ethnicity at specific mutation locations and breast/ovarian cancer phenotypes. Our cohort included 445 women with different ethnic backgrounds who underwent BRCA genetic testing between 1997 and 2010. Known clinical and pathologic characteristics were compared with Chi-Square Analysis or Fisher's Exact test as appropriate. The three most common mutation locations in BRCA1 (exons 2, 11, and 20) and BRCA2 (exons 10, 11, and 25) genes were chosen. Prevalence of BRCA1 exon 2 mutations were significantly higher in Ashkenazi Jewish ( AJ) women compared to Caucasians (41% versus 15%; p = 0.001). Similarly, AJ women with breast cancer were more likely to have BRCA1 exon 2 mutation (47% positivity in AJ women versus 0-12.5% positivity in other ethnicities; p = 0.004). Women carrying the exon 20 BRCA1 mutation had the highest probability of having combined breast and ovarian cancers compared to women carrying other exon mutations (p = 0.05). The median age at initial cancer diagnosis, phenotypic features of breast cancer tumors, and overall survival did not vary significantly by ethnicity or mutation location. Our data suggest that ethnicity does not affect age of onset, overall survival or confer different risks of breast and ovarian cancer development in BRCA carriers. These results also suggest that women carrying the exon 20 BRCA1 mutation may warrant mutation-specific counseling and be more aggressively managed for risk reduction. [ABSTRACT FROM AUTHOR]

Purpose: To compare health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors with sporadic CRC to those with hereditary cancer, specifically Lynch syndrome (LS). Methods: Participants completed a mailed self-administered questionnaire that assessed, among other things, demographics, clinical characteristics, and health-related quality of life. Using a case-case design, CRC survivors with LS or sporadic cancer were matched on age, sex, race/ethnicity, cancer stage, geography, and time since diagnosis. Participants were recruited from patient registries at The University of Texas MD Anderson Cancer Center (MD Anderson) (n = 33 LS; n = 75 sporadic) and through social media (n = 42 LS). The final sample included 71 LS and 74 sporadic CRC survivors. Results: For LS patients, the mean FACT-C HRQoL score was 84.8 (11.9) [Median = 86.0; Interquartile Range-17] compared to sporadic patients mean score of 85.8 (16.7) [Median = 92.0; Interquartile Range-21], which indicates high quality of life for both groups. LS patients and sporadic CRC patients had similar HRQoL mean scores across 7 different HRQoL metrics, with no significant differences between groups. Exploratory regression analyses indicate some differences in known predictors of HRQoL by group despite no bivariate differences. Conclusions: HRQoL is an important component of survivorship in CRC patients. Given the clinical distinctions between LS and sporadic patients, we expected to find significant differences between these patients. However, the patients' experiences/quality of life does not appear to illustrate such a clear dissimilarity within CRC survivors. Given the limited data in this area, larger studies, ideally with data obtained from multiple sites, is needed to better investigate the alignment between clinical determination and patient experience as well as to explore the relationship between HRQOL, treatment regimens, and health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer.Methods: This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined.Results: Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04).Conclusion: Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients. [ABSTRACT FROM AUTHOR]

Objective: The ideal number of neoadjuvant chemotherapy (NACT) cycles prior to interval tumor-reductive surgery (iTRS) for advanced ovarian cancer is poorly defined. We sought to assess survival stratified by number of NACT cycles and residual disease following iTRS in patients with advanced ovarian cancer with partial response (PR) or stable disease (SD) following 3-4 cycles of NACT., Methods: We retrospectively identified patients with advanced high-grade ovarian cancer (diagnosed 2/1/2013 to 2/1/2018) who received at least 3 cycles of NACT and iTRS and had a PR or SD. The population was divided into four groups based on the number of NACT cycles prior to iTRS and residual disease status after (CGR [complete gross residual] or incomplete resection [any amount of residual disease]): 1) 3-4 NACT cycles/CGR, 2) 3-4 NACT cycles/incomplete resection, 3) > 4 cycles/CGR, and 4) >4 cycles/incomplete resection. Overall survival (OS) and progression-free survival (PFS) were estimated using a Kaplan-Meier product-limit estimator and modeled using univariable and multivariable Cox proportional hazards analysis., Results: The cohort consisted of 265 patients with advanced high-grade ovarian cancer with a median age at diagnosis of 65 years. Most were White (87%), had serous histology (89%), and stage IV disease (57%), with an overall CGR rate of 81%. In a multivariable analysis receipt of >4 NACT cycles was not associated with worse PFS or OS (adjusted hazard ratio [aHR] 1.02, 95% CI 0.74-1.42; aHR 1.12, 95% CI, 0.73-1.72 respectively) than was receipt of 3-4 cycles. Any amount of residual disease was associated with worse PFS and OS regardless of the number of NACT cycles (aHR 1.56, 95% CI 1.09-2.22; aHR 2.38, 95% CI 1.52-3.72 respectively)., Conclusions: Residual disease was associated with worse survival outcomes regardless of the number of NACT cycles in patients with PR or SD after NACT for advanced high-grade ovarian cancer. These data suggest that the ability to achieve CGR should take precedence in decision-making regarding the timing of surgery., Competing Interests: Declaration of Competing Interest R.N., K.H.L, and J.A.R-H have nothing to disclose. N.D·F reports personal fees from Tesaro, personal fees from BMS/Pfizer, personal fees from Glaxo Smith Kline, outside the submitted work; B.M.F. and L.A.M report grants from NIH, during the conduct of the study. A.K.S reports grants from NIH Grants during the conduct of the study as well as consulting fees from Merck and Kiyatec, shareholder position in Biopath, other from Kiyatec, and research funding from M-Trap, outside the submitted work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The spectrum of cancers seen in a hospital based Lynch syndrome registry of mismatch repair gene mutation carriers was examined to determine the distribution of cancers and examine excess cancer risk. Overall there were 504 cancers recorded in 368 mutation carriers from 176 families. These included 236 (46.8 %) colorectal and 268 (53.2 %) extracolonic cancers. MLH1 mutation carriers had a higher frequency of colorectal cancers whereas MSH2, MSH6 and PMS2 mutation carriers had more extracolonic cancers although these differences were not statistically significant. Men had fewer extracolonic cancers than colorectal (45.3 vs. 54.7 %), whereas women had more extracolonic than colorectal cancers (59.0 vs. 41.0 %). The mean age at diagnosis overall for extracolonic cancers was older than for colorectal, 49.1 versus 44.8 years (P ≤ 0.001). As expected, the index cancer was colorectal in 58.1 % of patients and among the extracolonic index cancers, endometrial was the most common (13.8 %). A significant number of non-Lynch syndrome index cancers were recorded including breast (n = 5) prostate (n = 3), thyroid (n = 3), cervix (n = 3), melanoma (n = 3), and 1 case each of thymoma, sinus cavity, and adenocarcinoma of the lung. However, standardized incidence ratios calculated to assess excess cancer risk showed that only those cancers known to be associated with Lynch syndrome were significant in our sample. We found that Lynch syndrome patients can often present with cancers that are not considered part of Lynch syndrome. This has clinical relevance both for diagnosis of Lynch syndrome and surveillance for cancers of different sites during follow-up of these patients.

Low-grade (LG) serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors; yet the progression from serous borderline tumors to LG serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the 2 groups. Expression profiles were generated from 6 human ovarian surface epithelia, 8 serous borderline ovarian tumors (SBOTs), 13 LG serous ovarian carcinomas, and 24 high-grade (HG) serous ovarian carcinomas. The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors. This finding was validated by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues, and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P<0.005) among SBOT, LG, and HG tumors. SBOTs exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P=0.013) and HG (P=0.008) serous ovarian carcinoma groups. The progression of SBOT to LG serous ovarian carcinoma may involve the dedifferentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with LG and HG serous ovarian carcinomas.

Objective: To analyze the clinical behavior of patients with stage II-IV low-grade serous carcinoma of the ovary seen at our institution who underwent primary surgery followed by platinum-based chemotherapy., Methods: Patients with stage II-IV low-grade serous carcinoma of the ovary from 1978 to 2003 were identified using existing databases. Clinicopathologic information was obtained from medical records. Progression-free survival and overall survival were estimated by the method of Kaplan and Meier. The log-rank test was used to compare differences between survival curves. Univariable and multivariable analyses were performed using Cox proportional hazards regression., Results: We identified 112 eligible patients. Median age was 43 years.; 90% had stage III disease. Preoperative serum CA 125 was elevated in 86% of patients. The most common sites of extraovarian disease were omentum, fallopian tubes, pelvic peritoneum, and uterus. Response rate to platinum-based chemotherapy in 10 evaluable patients (15% of patients with gross residual disease) was 80%, and 42 patients underwent second-look surgery: microscopically negative findings, 2 (5%); microscopically positive disease, 13 (33%); macroscopically positive disease, 24 (62%); and insufficient information, 3 (7%). Median progression-free survival and overall survival times were 19.5 and 81.8 months. Persistent disease after primary chemotherapy was the only factor associated with shorter overall survival time (hazard ratio 3.46, 95% confidence interval 2.00-5.97, P<.001)., Conclusion: Metastatic low-grade serous carcinoma of the ovary is characterized by young age at diagnosis and prolonged overall survival. Segregating women with this diagnosis in future clinical trials is warranted.

Objective: The use of tamoxifen to prevent breast cancer and decrease recurrence is not controversial. However, the effect that tamoxifen may have in women with a history of breast cancer in whom endometrial cancer develops is unclear. The purpose of this study was to estimate whether a history of tamoxifen use is a prognostic factor for such patients., Methods: Between 1990 and 2002, patients seen at The University of Texas M. D. Anderson Cancer Center with a history of breast cancer who developed endometrial cancer were identified. Medical records were reviewed to identify clinical, pathologic, and outcome information., Results: Eighty-nine patients with a history of breast cancer in whom endometrial carcinoma developed were identified. Fifty-two percent (46/89) had a history of tamoxifen use (median duration 48 months; range 2-120 months). There were no significant differences in the clinical or pathologic features between tamoxifen users and nonusers. A history of tamoxifen use was associated with a shorter interval from breast cancer to endometrial cancer diagnosis (77.2 versus 121.3 months for nonusers; P =.01). There was no significant difference in overall survival between tamoxifen users and nonusers (39.2 months versus 48.3 months, P =.27), and there was no difference in endometrial cancer-specific survival duration between tamoxifen users and nonusers (55.7 versus 51.0 months, P =.92)., Conclusion: Among tamoxifen users, the interval from breast cancer to endometrial cancer diagnosis was significantly shorter than that in nonusers. In this cohort, a history of tamoxifen use was not associated with a worse overall or disease-specific survival.