High Risk Of Ovarian Cancer Research Articles

The Clinical Significance of Genetic Variation in Ovarian Cancer.

Genetic variation is a well-known contributor to the onset and progression of cancer. The goal of this study is to provide a comprehensive examination of the nucleotide and chromosomal variation associated with the onset and progression of serous ovarian cancer. Using a variety of computational and statistical methods, we examine the exome sequence profiles of genetic variants present in the primary tumors of 432 ovarian cancer patient samples to compute: (1) the tumor mutational burden for all genes and (2) the chromosomal copy number alterations associated with the onset/progression of ovarian cancer. Tumor mutational burden is reduced in the late vs. early stages, with the highest levels being associated with loss-of-function mutations in DNA-repair genes. Nucleotide variation and copy number alterations associated with known cancer driver genes are selectively favored over ovarian cancer development. The results indicate that genetic variation is a significant contributor to the onset and progression of ovarian cancer. The measurement of the relative levels of genetic variation associated with individual ovarian cancer patient tumors may be a clinically valuable predictor of potential tumor aggressiveness and resistance to chemotherapy. Tumors found to be associated with high levels of genetic variation may help in the clinical identification of high-risk ovarian cancer patients who could benefit from more frequent monitoring.

Multiple types of distress are prospectively associated with increased risk of ovarian cancer.

Few modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co-occurring distress-related factors are associated with ovarian cancer risk. Five distress-related factors were measured repeatedly over 21 years of follow-up: depression, anxiety, social isolation, widowhood, and, in a subset or women, posttraumatic stress disorder (PTSD). Cox proportional hazards models estimate relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer for a time-updated count of distress-related factors, in age-adjusted models, then further adjusted for ovarian cancer risk factors and behavior-related health risk factors. Across 1,193,927 person-years of follow-up, 526 incident ovarian cancers occurred. Women with ≥3 versus no distress-related psychosocial factors demonstrated increased ovarian cancer risk (HRage-adjusted = 1.71; 95% CI = 1.16, 2.52). No significant difference in ovarian cancer risk was observed in women with one or two versus no distress-related psychosocial factors. In the subsample with PTSD assessed, ≥3 versus no distress-related psychosocial factors was associated with twofold greater ovarian cancer risk (HRage-adjusted = 2.08, 95% CI = 1.01, 4.29). Further analysis suggested that women at highest ovarian cancer risk had PTSD co-occurring with any other distress-related factor (HR = 2.19, 95% CI = 1.20, 4.01). Adjusting for cancer risk factors and health behaviors minimally impacted risk estimates. Presence of multiple indicators of distress was associated with risk of ovarian cancer. When including PTSD as an indicator of distress, the association was strengthened.

Racial Differences in the Association of Endometriosis and Uterine Leiomyomas With the Risk of Ovarian Cancer.

To evaluate associations between endometriosis and uterine leiomyomas with ovarian cancer risk by race and the effect of hysterectomy on these associations. We used data from four case-control studies and two case-control studies nested within prospective cohorts in the OCWAA (Ovarian Cancer in Women of African Ancestry) consortium. The study population included 3,124 Black participants and 5,458 White participants, of whom 1,008 Black participants and 2,237 White participants had ovarian cancer. Logistic regression was used to calculate odds ratios (ORs) and 95% CIs for the associations of endometriosis and leiomyomas with ovarian cancer risk, by race, stratified by histotype and hysterectomy. The prevalences of endometriosis and leiomyomas were 6.4% and 43.2% among Black participants and 7.0% and 21.5% among White participants, respectively. Endometriosis was associated with an increased risk of endometrioid and clear-cell ovarian cancer in both racial groups (eg, OR for endometrioid tumors for Black and White participants 7.06 [95% CI 3.86-12.91] and 2.17 [95% CI 1.36-3.45], respectively, Phetereogeneity =.003). The association between endometriosis and ovarian cancer risk in White participants was stronger in those without hysterectomy, but no difference was observed in Black participants (all Pinteraction ≥.05). Leiomyomas were associated with an elevated risk of ovarian cancer only in those without hysterectomy in both Black (OR 1.34, 95% CI 1.11-1.62) and White (OR 1.22, 95% CI 1.05-1.41) participants (all Pinteraction ≥.05). Black and White participants with endometriosis had a higher risk of ovarian cancer, and hysterectomy modified this association among White participants. Leiomyomas were associated with an increased risk of ovarian cancer in both racial groups, with hysterectomy modifying the risk in both groups. Understanding how racial differences in access to care and treatment options (eg, hysterectomy) may help guide future risk reduction strategies.

Long-Term Health Consequences After Ovarian Removal at Benign Hysterectomy

More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions. To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions. Emulated target trial using data from a population-based cohort. Women in Denmark aged 20 years or older during 1977 to 2017. 142985 women with hysterectomy for a benign condition, 22974 with BSO and 120011 without. Benign hysterectomy with or without BSO. The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018. Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older. Age was a proxy for menopausal status. The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women. The Danish Cancer Society's Scientific Committee and the Mermaid Project.

Risk-Reducing Salpingectomy And Other Strategies For Prevention Of Ovarian And Tubal Carcinoma

Objective: To provide a review of most current evidence and data for risk-reducing strategies used in prevention of ovarian cancer. Methods of study selection: PubMed was used as a search tool for articles with key words focusing on current strategies on prevention of ovarian cancer such as “risk-reducing salpingectomy, “risk-reducing salpingo-oophorectomy, “salpingectomy with delayed oophorectomy”. General consensus and society guidelines from leading organizations such as Society of Gynecologic Oncology, American Cancer Society, and American College of Obstetricians and Gynecologists were reviewed and summarized in this review article with supporting evidence and research studies on most current riskreduction strategies for prevention of ovarian and tubal carcinoma. Result: There is growing evidence that high-grade serous ovarian carcinoma arises in the fallopian tube in the form of serous tubal intraepithelial carcinoma (STIC). Therefore, opportunistic salpingectomy has been increasingly offered at the time of routine benign gynecologic surgery. Risk-reducing bilateral salpingo-oophorectomy has been shown to reduce risk of ovarian cancer up to 90% and offered to women with high hereditary predisposition for ovarian cancer. Riskreducing salpingectomy with delayed oophorectomy (SDO) has been suggested in younger women to balance the effects of infertility and surgically induced menopause resulting from oophorectomy. Conclusion: Combined oral Contraceptive COCs confer long-term protection against ovarian cancer with reported 20% reduction for every 5 years of use, which have been cited as a confounding factor in most of the published studies. Women who used HRT (estrogen alone or combined estrogen and progesterone) carry 20% higher risk of ovarian cancer compared to never-users. The associated increased risk of cervical and breast cancer with COCs/HTR use, have recently let women prefer the RRSO over COCs for prevention of ovarian cancer. Bilateral risk reducing Salpingo-oophorectomy (RRSO) at the age of 40–45 in BRCA1 and 45–50 in BRCA2 mutation carriers is recommended to be the primary approach for risk reduction of ovarian cancer. There is well-supported evidence of lowering the risk of ovarian cancer in high-risk population by 90%. The American college of obstetrics and gynecology committee opinion, recommended opportunistic salpingectomy for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication. Bilateral salpingectomy at the time of cesarean delivery is recommended to replace the tubal ligation as the method of choice for sterilization performed with cesarean delivery. The novel alternative procedure of Risk-reducing Salpingectomy with delayed risk-reducing oophorectomy (RRSO-RRO) have growing attention as a better alternative to improve the menopause-related morbidity and quality of life.

Real-world outcomes associated with use of front-line bevacizumab in ovarian cancer

BackgroundIn the pivotal ICON7 study, addition of bevacizumab to front-line treatment of ovarian cancer (OC) significantly improved overall survival (OS) (p = 0.03) in a high-risk subgroup of patients with suboptimally debulked/unresectable stage III or IV disease, leading to approval in Ontario, Canada in March 2016. Here we describe utilization of bevacizumab for front-line, high-risk OC and determine outcomes in routine clinical practice. MethodsProvincial administrative databases were utilized to identify all patients treated with front-line bevacizumab following its approval. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. A comparative effectiveness analysis was performed to determine mOS pre- (2006–2016) and post- (2016–2019) approval. ResultsFrom March 2016 to October 2019, 282 patients received bevacizumab. Mean age was 64 years old, and 58% had stage IV disease. Median survival was 29 months and was longer in stage III (37 months) compared to stage IV disease (28 months). In a comparative effectiveness analysis of patients with stage IV serous OC, post-approval uptake of bevacizumab was low (23%). Median OS was similar pre (26 months) and post (27 months) approval (HR 0.92, 0.75–1.12, p = 0.383). ConclusionsSurvival in real-world patients treated with front-line bevacizumab is shorter than in pivotal clinical trials. Survival in stage IV serous patients has not significantly improved post public reimbursement of bevacizumab. This analysis was limited by poor uptake, however mOS was similar in patients who did and did not receive bevacizumab.

Abstract P5-03-16: Changes in preferences for ovarian cancer prevention strategies during the COVID-19 pandemic: Results of a discrete choice experiment

Abstract Background: The COVID-19 pandemic influenced patient health care decisions, but there is little information about the pandemic’s impact on decisions about cancer risk reduction. This includes women at elevated risk of breast or ovarian cancer considering risk-reducing salpingo-oophorectomy (RRSO), risk-reducing salpingectomy (RRS), or other preventive measures. During the pandemic patients needed to balance their concerns about cancer risk reduction with their risks associated with elective health procedures, a risk which changed as vaccines became available. Methods: To address the impact of the COVID-19 pandemic on cancer prevention decision making, we recruited N=396 pre-menopausal women with a personal history of breast cancer or familial history suggestive of increased breast and/or ovarian cancer risk between 4/2019 and 3/2022. We conducted a discrete choice experiment in which patients were asked to choose between two scenarios that specified type of surgery (RRSO, RRS vs. non-surgical surveillance), age of menopause (natural versus immediate), quality of menopausal symptoms (mild, moderate, severe), and risk of ovarian cancer, heart disease, or osteoporosis. Risk of ovarian cancer for the scenarios provided varied in discrete intervals from 0% to 40%. We examined temporal trends during the pandemic using interactions with time coinciding approximately with the beginning of pandemic, peak vaccination period, and the Omicron wave. Results: We identified significant temporal interactions on a woman’s prevention decisions. In 2019, women at higher risk of ovarian cancer were more likely to choose prevention scenarios that favored lower ovarian cancer risk (odds ratio [OR] = 0.48; 95% CI = 0.37, 0.69 per 10% increase in ovarian cancer risk difference). This association decreased through the pre-vaccine period of 2020 by OR=2.61/month (95% CI = 1.21, 5.65). By June 2020, the effect of a 10% increase in ovarian cancer risk on intervention choice had attenuated substantially (OR=0.84, 95% CI 0.67, 1.00). By January 2022, the effect strengthened (OR= 0.69, 95% CI .49, .88), but had not reached pre-pandemic levels. Before 3/2020, natural age of menopause (versus immediate) had a strong impact on the choice of a scenario (OR=3.56, 95% CI 1.65-7.65). At the beginning of the pandemic, the effect was reduced by 0.47/month (95% CI 0.22-0.99). The rate of attenuation slowed over time, such that the effect of having a natural age of menopause on choice was OR= 1.56 (95% CI 0.65, 2.46) by January 2022. Tests for temporal interactions were statistically significant for both ovarian cancer risk and age of menopause. Conclusions: Our results suggest that over the course of the pandemic, women seemed more accepting of higher risks of ovarian cancer and immediate (post treatment) menopause when considering preventive options. There was an inverse U shape curve of the effect of ovarian cancer risk on choices over time (Figure A), but the strength of the relationship had not reached pre-pandemic levels by January 2022. This may reflect patient tolerance for side effects as the pandemic evolved. These results suggest that factors such as ovarian cancer risk and delay of menopause influenced personal prevention choices, but that these choices were influenced by events related to events that hallmarked the COVID-19 pandemic. Citation Format: Brian Egleston, Mary Daly, Kaitlyn Lew, Lisa Bealin, Alexander Husband, Jill Stopfer, Pawel Przybysz, Olga Tchuvatkina, Yu-Ning Wong, Judy Garber, Timothy Rebbeck. Changes in preferences for ovarian cancer prevention strategies during the COVID-19 pandemic: Results of a discrete choice experiment. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-16.

Detection and Genotyping of Human Papillomavirus (HPV16/18), Epstein–Barr Virus (EBV), and Human Cytomegalovirus (HCMV) in Endometrial Endometroid and Ovarian Cancers

The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.

Abstract P6-02-08: Identifying preferences that may motivate choice of ovarian cancer risk prevention strategies using a discrete choice experiment

Abstract Background: Women with a familial or hereditary risk for ovarian cancer are at a much greater risk of developing ovarian cancer compared with women in the general population. This high risk demands prevention strategies to reduce ovarian cancer incidence and mortality. Currently there is little information about how women with a hereditary risk for ovarian cancer make trade-offs when choosing among prevention strategies and their associated risks. In anticipation of the likelihood that when given more personalized risk estimates, patients may have different preferences based on their mutation specific cancer risk as well as demographic and clinical factors, it is critical that we have the necessary information to develop counseling models that are tailored to individual patients’ preferences for cancer risk reduction and tolerance of associated risks. Methods: We performed a discrete choice experiment to investigate how women at higher risk of ovarian cancer weigh benefits (e.g. reduced risk of ovarian) versus costs (e.g. increased risk of heart disease) in choosing a treatment strategy. N=396 pre-menopausal women with a personal history of breast cancer or familial history suggestive of increased breast and/or ovarian cancer risk were surveyed from August, 2019, to January, 2022. Participants were asked to choose between two sets of attributes that specified type of surgery (risk-reducing salpingo-oophorectomy [RRSO], risk reducing salpingectomy [RRS] vs. non-surgical surveillance), age of menopause (natural versus immediate), quality of menopausal symptoms (mild, moderate, severe), and risk of ovarian cancer, heart disease, or osteoporosis. Risks of disease varied in discrete intervals. We fit a Bradley-Terry logistic regression to estimate preferences. The binary response was the randomly generated choice set selected versus the set not selected. Results: Women were more likely to choose sets with either surveillance (odds ratio [OR]= 1.28, 95% confidence interval [CI] 0.98, 1.67) or RRSO (OR= 1.39, 95% CI 1.07, 1.81) over RSS. In weighing trade-offs in the choice sets that included type of surgery, women had a stronger independent preference for reducing the risk of ovarian cancer (OR= 0.66 of choosing set per 10% increase in risk, 95% CI 0.62, 0.71) than in reducing the risk of osteoporosis (OR= 0.82 per 10% increase, 95% CI 0.75, 0.90) or heart disease (OR = 0.82 per 10% increase, 95% CI 0.76,0.88). Women also had a strong preference for delaying the expected age of ovarian cancer (OR= 1.34 per 10-year increase in age, 95% CI 1.19, 1.51). Women had strong preferences for having a natural age of menopause (OR= 1.58 compared to immediate menopause post-treatment, 95% CI 1.27, 1.95), and better less severe symptoms (OR= 0.65 for each ordinal increase in the severity of symptoms, 95% CI 0.60, 0.70). Conclusions: Our results suggest that women may prefer either surveillance or the most extensive type of surgery (RRSO) over more limited surgery (RRS). In weighing trade-offs, reducing the risk of ovarian cancer seemed to be more important than reducing the risk of osteoporosis or heart disease. Still, having a natural age of menopause and reducing the severity of symptoms could motivate the choice of treatment. Our work will allow us to estimate thresholds of measured factors that may motivate women to choose a specific treatment strategy. Citation Format: Mary Daly, Brian Egleston, Kaitlyn Lew, Lisa Bealin, Alexander Husband, Jill Stopfe, Pawel Przybysz, Olga Tchuvatkina, Yu-Ning Wong, Judy Garber, Timothy Rebbeck. Identifying preferences that may motivate choice of ovarian cancer risk prevention strategies using a discrete choice experiment. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-08.

Association of Frequent Aspirin Use With Ovarian Cancer Risk According to Genetic Susceptibility

Frequent aspirin use is associated with reduced ovarian cancer risk, but it is unknown whether genetic factors modify this association. Understanding effect modifiers is important given that any use of aspirin for ovarian cancer chemoprevention will likely need to focus on specific higher-risk subgroups. To evaluate whether the association between frequent aspirin use and ovarian cancer is modified by a polygenic score (PGS) for nonmucinous ovarian cancer. We pooled individual-level data from 8 population-based case-control studies from the Ovarian Cancer Association Consortium conducted in the US, UK, and Australia between 1995 and 2009. We included case patients and control participants with both genetic data and data on frequent aspirin use. Case patients with mucinous ovarian cancer were excluded. Data were analyzed between November 1, 2021, and July 31, 2022. Frequent aspirin use, defined as daily or almost daily use for 6 months or longer. The main outcome was nonmucinous epithelial ovarian cancer. We used logistic regression to estimate odds ratios (ORs) and 95% CIs and likelihood ratio tests to investigate effect modification by the PGS. There were 4476 case patients with nonmucinous ovarian cancer and 6659 control participants included in this analysis. At study enrollment, the median (IQR) age was 58 (50-66) years for case patients and 57 (49-65) years for control participants. Case patients and control participants self-reported that they were Black (122 [3%] vs 218 [3%]), White (3995 [89%] vs 5851 [88%]), or of other race and ethnicity (348 [8%] vs 580 [9%]; race and ethnicity were unknown for 11 [0%] vs 10 [0%]). There were 575 case patients (13%) and 1030 control participants (15%) who reported frequent aspirin use. The 13% reduction in ovarian cancer risk associated with frequent aspirin use (OR, 0.87 [95% CI, 0.76-0.99]) was not modified by the PGS. Consistent ORs were observed among individuals with a PGS less than (0.85 [0.70-1.02]) and greater than (0.86 [0.74-1.01]) the median. Results were similar by histotype. The findings of this study suggest that genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not appear to modify the protective association between frequent aspirin use and ovarian cancer risk. Future work should continue to explore the role of aspirin use for ovarian cancer prevention among individuals who are at higher risk for ovarian cancer.

Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study.

Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20-30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.

The Influence of Laparoscopic Benign Hysterectomy in Sexual Function

Objectives: Hysterectomy is the most frequent major surgery performed worldwide in women and in recent years most studies include validated instruments to measure sexual quality of life pre and post operatively. The present review assesses sexual function following abdominal hysterectomy for benign pathology, especially in relation to minimally invasive surgery: laparoscopic and robotics according to different considerations. Mechanism: The uterus has traditionally been considered a sexually functioning organ, so uterine removal has been associated with negative outcomes on patients’ sexual function despite limited and controversial evidence. By contrast, reviews conducted in recent years conclude that hysterectomies performed for benign uterine pathology improve patients’ sexual function and quality of life. Findings in brief: Some factors associated with surgery have been specially assessed: the combination of hysterectomy with bilateral oophorectomy in patients with benign pathology can lead to alterations in sexual function and should be restricted only to patients at high risk of ovarian cancer, moreover, there is no current scientific evidence to justify performing a subtotal hysterectomy to preserve or improve sexual quality of life over total hysterectomy. Conclusions: postoperative sexual changes have not been demonstrated to mainly depend on surgical approach, in fact, patients who had sexual concerns prior surgery will continue to present them after hysterectomy despite of the vaginal cuff suture approach.

Abstract C105: Racial differences in the association of endometriosis and fibroids with risk of ovarian cancer

Abstract PURPOSE: Women with endometriosis have a 2 to 3-fold greater risk of endometrioid and clear cell ovarian cancer than other women, based on estimates from studies predominantly of White women. Fibroids have not been consistently associated with ovarian cancer risk but are the most common indication for hysterectomies in the U.S. Hysterectomy has been associated with lower ovarian cancer risk in subgroups of women including those with fibroids; thus fibroids may indirectly impact ovarian cancer risk. We evaluated the association of endometriosis and fibroids with ovarian cancer risk among Black and White women, taking into consideration the impact of hysterectomy. METHODS: We used data from six studies in the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium. Participants included 2,995 Black women and 5,281 White women. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between endometriosis and fibroids with ovarian cancer risk, overall, by race, and stratified by histotype. We also assessed effect modification by hysterectomy. RESULTS: Overall the prevalences of endometriosis and fibroids were 6.4% and 43.2% among Black women and 7.0% and 21.5% among White women, respectively. Endometriosis was associated with an increased risk of endometrioid and clear cell ovarian cancer in Black and White women. Among Black women the association was strongest for endometrioid tumors (OR=7.06; 95% CI=3.86-12.91) compared to White women (OR=2.17; 95% CI=1.36-3.45) with a significant difference by race (phetereogeneity=0.003). When stratified by hysterectomy the association between endometriosis and ovarian cancer risk in White women was stronger in those who did not report a hysterectomy. However, in Black women, the elevated risk of ovarian cancer among women with endometriosis was present among those with and without hysterectomy. Fibroids were associated with a slightly elevated risk of ovarian cancer in Black (OR=1.34; 95% CI=1.11-1.62) and White women (OR=1.22; 95% CI=1.05-1.41). For both groups, the association was present only in those who did not report a hysterectomy. Black women who had a history of fibroids and no hysterectomy had a 53% greater odds of ovarian cancer (95% CI=1.23-1.89) compared to those without fibroids, while there was no association with fibroids in the hysterectomy group (OR=0.92, 95% CI=0.62-1.36) (pinteraction=0.05). A similar pattern was observed among White women, but the interaction was not significant (pinteraction=0.21). CONCLUSION: Both Black and White women with endometriosis had a higher risk of ovarian cancer, and hysterectomy modified this association only among White women. Fibroids were associated with modestly increased risk of ovarian cancer among Black and White women, with hysterectomy modifying the risk in both groups. Further research is needed to understanding how racial differences in diagnoses of these conditions, and differential access to care and treatment options, impact or modify ovarian cancer risk. Citation Format: Holly Harris, Lauren Peres, Courtney Johnson, Kristin Guertin, Alicia Beeghly-Fadiel, Elisa Bandera, Traci Bethea, Charlotte Joslin, Anna Wu, Patricia Moorman, Heather Ochs-Balcom, Jessica Petrick, Veronica Setiawan, Lynn Rosenberg, Joellen Schildkraut, Evan Myers. Racial differences in the association of endometriosis and fibroids with risk of ovarian cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C105.

Risk of ovarian cancer in women who give birth after assisted reproductive technology (ART)-a registry-based Nordic cohort study with follow-up from first pregnancy.

There is concern that assisted reproductive technology (ART) may increase ovarian cancer risk, but previous studies are inconclusive. We compared ovarian cancer risk for women who gave birth after ART vs natural conception. Through linkage of nationwide registry data, we followed 3,303,880 initially nulliparous women in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015) from first pregnancy ≥22 weeks to ovarian cancer, emigration, death or end of follow-up (2014/2015). We estimated hazard ratios (HRs), adjusting for age, parity, maternal birth year and country, and for body mass index and smoking in subsamples. Mean age at first birth was 27.7 years. During a mean follow-up of 14.4 person-years, 2683 participants (0.08%) developed ovarian cancer; 135 after ART and 2548 after natural conception only (incidence rates 11.6 and 5.5 per 100,000 person-years, respectively). The risk was higher for women who ever gave birth after ART (HR 1.70, 95% confidence interval 1.42-2.03) compared to natural conception. Associations were stronger for conventional in vitro fertilisation than for intracytoplasmic sperm injection. Among parous women, ART-conception was associated with a higher risk of ovarian cancer than natural conception. Further studies should decipher whether this is causal or confounded by infertility or other factors.

A random forest-based metabolic risk model to assess the prognosis and metabolism-related drug targets in ovarian cancer

As one of the most common gynecologic malignant tumors, ovarian cancer is usually diagnosed at an advanced and incurable stage because of its early asymptomatic onset. Increasing research into tumor biology has demonstrated that abnormal cellular metabolism precedes tumorigenesis, therefore it has become an area of active research in academia. Cellular metabolism is of great significance in cancer diagnostic and prognostic studies. In this study, we integrated The Cancer Genome Atlas dataset with multiple Gene Expression Omnibus ovarian cancer datasets, identified 17 metabolic pathways with prognostic values using the random forest algorithm, constructed a metabolic risk scoring model based on metabolic pathway enrichment scores, and classified patients with ovarian cancer into two subtypes. Then, we systematically investigated the differences between different subtypes in terms of prognosis, differential gene expression, immune signature enrichment, Hallmark signature enrichment, and somatic mutations. As well, we successfully predicted differences in sensitivity to immunotherapy and chemotherapy drugs in patients with different metabolic risk subtypes. Moreover, we identified 5 drug targets associated with high metabolic risk and low metabolic risk ovarian cancer phenotypes through the weighted correlation network analysis and investigated their roles in the genesis of ovarian cancer. Finally, we developed an XGBoost classifier for predicting metabolic risk types in patients with ovarian cancer, producing a good predictive effect. In light of the above study, the research findings will provide valuable information for prognostic prediction and personalized medical treatment of patients with ovarian cancer.

Identifying women at high risk of ovarian cancer

The International Journal of Integrated Care (IJIC) is an online, open-access, peer-reviewed scientific journal that publishes original articles in the field of integrated care on a continuous basis.IJIC has an Impact Factor of 2.913 (2021 JCR, received in June 2022)The IJIC 20th Anniversary Issue was published in 2021.

A combined clinical and genetic model for predicting risk of ovarian cancer.

Women with a family history of ovarian cancer or a pathogenic or likely pathogenic gene variant are at high risk of the disease, but very few women have these risk factors. We assessed whether a combined polygenic and clinical risk score could predict risk of ovarian cancer in population-based women who would otherwise be considered as being at average risk. We used the UK Biobank to conduct a prospective cohort study assessing the performance of 10-year ovarian cancer risks based on a polygenic risk score, a clinical risk score and a combined risk score. We used Cox regression to assess association, Harrell's C-index to assess discrimination and Poisson regression to assess calibration. The combined risk model performed best and problems with calibration were overcome by recalibrating the model, which then had a hazard ratio per quintile of risk of 1.338 [95% confidence interval (CI), 1.152-1.553], a Harrell's C-index of 0.663 (95% CI, 0.629-0.698) and overall calibration of 1.000 (95% CI, 0.874-1.145). In the refined model with estimates based on the entire dataset, women in the top quintile of 10-year risk were at 1.387 (95% CI, 1.086-1.688) times increased risk, while women in the top quintile of full-lifetime risk were at 1.527 (95% CI, 1.187-1.866) times increased risk compared with the population. Identification of women who are at high risk of ovarian cancer can allow healthcare providers and patients to engage in joint decision-making discussions around the risks and benefits of screening options or risk-reducing surgery.

Clinical calculator redefines prognosis for high-risk early-stage ovarian cancers and potential to guide treatment in the adjuvant setting

ObjectiveTo determine the utility of a clinical calculator to redefine prognosis and need for chemotherapy among patients with early-stage high-risk epithelial ovarian cancer. MethodsData were abstracted for stage I-II, high-risk ovarian cancer from the National Cancer Database from years 2005 to 2015. Based on demographic, pathologic, surgical, and laboratory characteristics, a clinical score was developed using Cox regression. Propensity score weighting was used to adjust for differences between patients who did and did not receive chemotherapy. ResultsOf 8188 patients with early-stage high-risk ovarian cancer, 6915 (84%) did and 1273 (16%) did not receive chemotherapy. A clinical calculator was created utilizing age, stage, histology, grade, tumor size, number of pelvic and paraaortic lymph nodes examined, the presence of malignant ascites, and CA125. The calculator divided patients into low, moderate, and high-risk groups with 5-year OS (overall survival) of 92%, 82%, and 66%, and 10-year OS of 85%, 67%, and 44%, respectively. Chemotherapy improved 5-year OS and 10-year OS in the high-risk group (56% to 73%; p < 0.001, 34% to 48%; p < 0.001). The moderate risk group had improved 5-year OS (80% to 85%; p = 0.01) but not 10-year OS (66% to 66%; p = 0.13). Chemotherapy did not improve 5-year or 10-year OS in low-risk patients (93% to 92%, p = 1.0, 86% to 84%, p = 0.99). ConclusionsThe prognosis among high-risk early-stage ovarian cancer patients is heterogeneous. This calculator may aid in patient-centered counseling regarding potential treatment benefits.

History of Endometriosis Is Independently Associated with an Increased Risk of Ovarian Cancer.

Background: Endometriosis is a complex gynecologic disorder that has been associated with a higher risk of ovarian cancer. The purpose of this work is to determine to what extent a history of endometriosis is a risk factor for ovarian cancer in a Spanish population. Methods: A retrospective case–control study was conducted using de-identified data from the Spanish National Health System’s “Primary Care Clinical Database” and “Hospital Minimum Basic Data Set” for the period 2013–2017. Multiple logistics regression analysis was conducted to determine associations between ovarian cancer and endometriosis controlled by sociodemographic characteristics and comorbidities. Results: Data from 608,980 women were analyzed, with 4505 presenting ovarian cancer. Endometriosis patients were shown to have a 2.66-fold increased risk of ovarian cancer when compared to those who did not have endometriosis by controlling age and other relevant comorbidities. Conclusions: This case–control study based on clinical administrative data has found that a history of endometriosis is independently associated with an increased risk of ovarian cancer. More research is needed to determine if a history of endometriosis affects survival results in ovarian cancer patients.

MiR-3653-3P EXPRESSION IN PERIPHERAL BLOOD OF PATIENTS WITH OVARIAN CARCINOMA

Ovarian cancer is a late-stage cancer with early and frequent recurrence, and there is still no effective treatment.There are no sensitive and specific biomarkers to be used effectively in the early diagnosis and treatment of the disease.Those currently used in the clinic are extremely insufficient for the early diagnosis and treatment follow-up of the disease, in terms of accurately determining the minimal residual disease.Many studies have shown that deregulation or dysfunction of miRNAs in the small non-coding RNA class contributes to cancer development However, it is known that the expressions of a number of miRNAs differ in ovarian cancer. Examining the expression patterns of known miRNAs in cancer research by comparing them between patients and healthy people is extremely important in terms of finding disease-specific biological markers, and determining the roles of these molecules in the pathogenesis of ovarian cancer is also significant.In the thesis study presented, the expression profile of miR-3653-3p was investigated in a control group consisting of 150 high-risk ovarian cancer patients and 100 healthy individuals, and both groups were compared with each other.It was found that the expression level of miR-3653-3p in the peripheral blood of ovarian cancer patients was 9.49 times higher than the control groups and the results were shown to be statistically significant(p = 0.00).In addition to these results, whether miR-3653-3p can be used as a non-invasive biomarker in peripheral blood for ovarian cancer was evaluated by ROC analysis and it was shown that the molecule in question was a statistically significant biomarker.