Meaningful Patient Engagement in Adolescent and Young Adult (AYA) Cancer Research: A Framework for Qualitative Studies.

Over the last two decades, patient engagement in cancer research has evolved significantly, especially in addressing the unique challenges faced by adolescent and young adult (AYA) cancer populations. This paper introduces a framework for meaningful engagement with AYA cancer patient research partners, drawing insights from the "FUTURE" Study, a qualitative study that utilizes focus groups to explore the impact of cancer diagnosis and treatment on the sexual and reproductive health of AYA cancer patients in Canada. The framework's development integrates insights from prior works and addresses challenges with patient engagement in research specific to AYA cancer populations. The framework is guided by overarching principles (safety, flexibility, and sensitivity) and includes considerations that apply across all phases of a research study (collaboration; iteration; communication; and equity, diversity, and inclusion) and tasks that apply to specific phases of a research study (developing, conducting, and translating the study). The proposed framework seeks to increase patient engagement in AYA cancer research beyond a supplementary aspect to an integral component for conducting research with impact on patients.

Outcomes After Surgery at an Interdisciplinary Centre of Expertise for Endometriosis and Pelvic Pain in Canada: A Prospective Cohort Study.

OBJECTIVES: To prospectively evaluate pain-related quality-of-life (Endometriosis Health Profile-30 [EHP-30] pain subscale) after surgery at an interdisciplinary centre of expertise for endometriosis and pelvic pain. METHODS: A prospective cohort study was completed of persons undergoing surgical management for pelvic pain between December 2013 and July 2016 at an interdisciplinary tertiary referral centre for pelvic pain and endometriosis. We compared the change in EHP-30 scores for the following scenarios: (1) type of surgery (conservative surgery vs. hysterectomy), (2) stage of endometriosis (stage I/II vs. III/IV), and (3) age (age <40 vs. age ≥40 years). We used mixed-effects models to evaluate changes in pain during follow-up after surgery. RESULTS: Overall, 595 individuals met our inclusion criteria; the follow-up rate was 65.9% (392/595). In total, 436 (73.3%) underwent conservative surgery, while 159 (26.7%) underwent hysterectomy. Improvements in pain-related quality-of-life were seen for both conservative surgery and hysterectomy but greater improvements were seen with hysterectomy (P < 0.001). For conservative surgery, similar improvements in quality-of-life were observed regardless of endometriosis stage (I/II vs. III/IV) (P = 0.84) or age (<40 or ≥40 years old) (P = 0.87). We also observed similar improvements in quality-of-life regardless of stage (P = 0.24) or age (P = 0.71) after hysterectomy. CONCLUSIONS: At an interdisciplinary centre of expertise, there were significant improvements in quality-of-life after endometriosis surgery. These improvements were seen for both conservative surgery and hysterectomy (although greater improvement with the latter), for early and advanced stage disease, and younger and older patients.

Incidence and risk factors of venous and arterial thromboembolic events among patients with ovarian cancer- data from a large Canadian database.

OBJECTIVES: To determine the incidence of thromboembolic events (TEEs) in ovarian cancer patients and to identify risk factors that are significantly associated with the development of venous thromboembolism (VTE), arterial thromboembolism (ATE), or overall TEEs in this population. METHODS: This is a retrospective cohort study of 4491 patients with epithelial ovarian cancer identified in the British Columbia cancer registry between 1996 and 2017. The presence of TEEs and risk factors were identified in administrative health records from fee-for-service provider visits and hospital data using ICD-9-CM and ICD-10-CM billing codes. Statistical analysis was performed using Chi-squared test and Fischer's exact test. RESULTS: Of 4491 patients with epithelial ovarian cancer included in this study, 1.74% experienced ATE and (9.44%) experienced VTE. There was a significant association found between the occurrence of TEEs and all-cause mortality. Sepsis was significantly associated with both venous and arterial thromboembolism. The top three risk factors for arterial thromboembolism included peripheral vascular disease (PVD), open wound, and aneurysm. CONCLUSIONS: Risk factors predictive of thrombosis in ovarian cancer patients are not consistent between ATE and VTE, thus thrombotic events should not be combined for analysis. Differential thrombosis risk assessment is needed to improve prevention strategies and guide thromboprophylaxis for these patients.

Complications after opportunistic salpingectomy compared with tubal ligation at cesarean section: a retrospective cohort study.

OBJECTIVE: To compare perioperative and postoperative complications in patients who underwent opportunistic salpingectomy (OS) (removal of the fallopian tubes for ovarian cancer risk reduction during another surgery) at the time of cesarean section (C-section) with those in patients who underwent tubal ligation. DESIGN: A population-based, retrospective cohort study. SETTING: British Columbia, Canada. PATIENT(S): A total of 18,184 patients were included in this study, of whom 8,440 and 9,744 underwent OS and tubal ligation, respectively. INTERVENTION(S): Patients who underwent OS during a C-section were compared with those who underwent tubal ligation during a C-section. MAIN OUTCOME MEASURE(S): We examined the perioperative outcomes, including operating room time, length of hospital stay, surgical complications such as infections, anemia, incision complications, injury to a pelvic organ, or operating room return; postoperative complications, including physician visits for a postoperative infection or visits that resulted in ultrasound or laboratory examinations and hospital readmissions in the 6 weeks after discharge; and likelihood to fill a prescription for antibiotics or analgesics. RESULT(S): The OS group had decreased odds of perioperative complications compared with the tubal ligation group (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.61-0.99). Patients who underwent OS did not have increased risks of physician visits for surgical complications, such as infection, or hospital readmissions in the 6 weeks after hospital discharge. In addition, these patients had 18% and 23% increased odds of filling prescriptions for nonsteroidal anti-inflammatory drugs (aOR, 1.18; 95% CI, 1.07-1.28) and opioids (aOR, 1.23%; 95% CI, 1.12-1.35), respectively. CONCLUSION(S): In this population-based, real-world study of OS at C-section, we report decreased perioperative complications and no difference in postoperative complications between patients who underwent OS and those who underwent tubal ligation. Patients who underwent OS had an increased likelihood of filling a prescription for nonsteroidal anti-inflammatory drugs and opioids in the 6 weeks after hospital discharge. This result should be interpreted with caution because we did not have data on over-the-counter medication use and, thus, not all prescription analgesics were captured in our data. Our data suggest that OS after C-section is a safe way to provide effective contraception and ovarian cancer risk reduction.

The Association Between Endometriosis Treatments and Depression and/or Anxiety in a Population-Based Pathologically Confirmed Cohort of People with Endometriosis.

Objective: Endometriosis patients have a high rate of co-occurring anxiety and depression. There is currently no literature investigating how this may affect endometriosis treatment and outcomes. This study examines the prevalence of depression and anxiety in a pathologically confirmed population-based endometriosis cohort and examines how endometriosis treatments and outcomes differ by the presence of co-occurring depression and/or anxiety. Methods: This retrospective cohort study using population-based administrative data sets included pathologically confirmed endometriosis patients identified from the complete pathology records of Vancouver Coastal Health Authority (British Columbia, Canada) between 2000 and 2008. These data were linked with population-based health data for follow-up to 2017. Bivariate analyses assessed differences between patients with depression and/or anxiety and those without. Odds ratios (ORs) were calculated to assess the odds of binary postsurgical outcomes. Results: Our final cohort consisted of 3815 patients. There were 603 patients (15.8%) with depression and/or anxiety. They were more likely to visit a physician for pelvic pain, more likely to take some hormonal medications, and more likely to fill prescription-level analgesics, including opioids both before and after surgery. They also had a significantly higher risk of reoperation for their endometriosis than people without co-occurring depression and/or anxiety (OR 1.32, 95% confidence interval [CI]: 1.07-1.61). Conclusion: Endometriosis patients with co-occurring depression and/or anxiety used more health services for pain, including prescription-level analgesics, and were more likely to have an endometriosis reoperation. We recommend that future study should aim to better understand the direction of this association between depression and/or anxiety and increased health services use.

Opportunistic Salpingectomy Between 2017 and 2020: A Descriptive Analysis.

OBJECTIVES: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during another pelvic surgery for the purpose of ovarian cancer prevention. Herein, we describe the rates of OS at the time of hysterectomy and tubal sterilization between 2017 and 2020. METHODS: This study uses the Canadian Institute of Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories except for Quebec between the fiscal years 2017 and 2020. A descriptive analysis on all people aged 15 years and older who had hysterectomies or tubal sterilizations was conducted to determine the proportion of hysterectomies that included bilateral salpingectomy (OS) and the proportion of tubal sterilizations that were OS compared to tubal ligation. RESULTS: There were 174 006 people included in the study. The proportion of hysterectomies that included OS increased from 31.7% in 2017 to 39.9% by 2020. With respect to tubal sterilizations, rates of OS increased from 26.3% of all tubal sterilizations in 2017 to 42.5% in 2020. British Columbia remained the jurisdiction with the highest rates of OS, but rates increased significantly in many jurisdictions, particularly at the time of tubal sterilization. CONCLUSION: The rates of OS have continued to increase in all Canadian jurisdictions following the official Society of Obstetricians and Gynaecologists of Canada recommendation to consider OS in 2015. Assuming that all tubal ligations could have been OS and 75% of hysterectomies with ovarian conservation could have included OS, our data indicate 76 932 missed opportunities for ovarian cancer prevention.

A framework for assessing interactions for risk stratification models: the example of ovarian cancer.

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.

Reproductive Health Outcomes among Adolescent and Young Adult Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis (SRMA) aimed to synthesize the current literature on the impacts of adolescent and young adult (AYA, ages 15-39 years) cancer on reproductive health outcomes. METHODS: EMBASE and Medline were searched from 1 January 2000 to 26 January 2022 for observational studies that included individuals with AYA cancer and controls which evaluated reproductive health outcomes. We used random effects models and 95% confidence intervals to obtain pooled measures of associations between AYA cancer, cancer treatment, and reproductive health outcomes. RESULTS: The search identified 8625 articles; 21 were included. 62 reproductive outcomes were assessed and classified according to a sex-based framework as fetal/neonatal (n = 26), maternal (n = 11), fetal/neonatal-maternal (n = 23), and maternal-paternal (n = 2). Meta-analyses of crude estimates showed significant associations between AYA cancer and outcomes including preterm birth (pooled odds ratio [pOR] 1.31; 95% CI: 1.22, 1.42), gestational diabetes (pOR 1.43; 95% CI: 1.03, 1.99), and fertility treatment (pOR 2.66; 95% CI 1.71, 4.11). We also found higher odds of preterm birth (pOR 1.65; 95% CI: 1.21, 2.26) and low APGAR score at birth (pOR 2.03; 95% CI: 1.32, 3.13) among AYA cancer patients who received radiation compared to controls. CONCLUSIONS: Our SRMA quantified impacts of AYA cancers and treatments on several reproductive health outcomes.

Long-Term Non-Cancer Risks in People with BRCA Mutations following Risk-Reducing Bilateral Salpingo-Oophorectomy and the Role of Hormone Replacement Therapy: A Review.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35-45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse psychosocial, cardiovascular, bone, and cognitive health consequences. While these health consequences have been thoroughly studied in the general population, little is known about the long-term health outcomes in the BRCA population. Hormone replacement therapy (HRT) until the average age of natural menopause can help mitigate these health risks, yet the initiation of HRT is a complex decision among BRCA carriers due to concern of increasing the already high risk of breast cancer in these people. This review summarizes the current research on long-term non-cancer risks in BRCA carriers following RRBSO-induced premature surgical menopause, and highlights the existing evidence in support of HRT use in this population.

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery.

OBJECTIVE: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. METHODS: This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. RESULTS: Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53). CONCLUSIONS: The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Reoperation and pain-related outcomes after hysterectomy for endometriosis by oophorectomy status.

BACKGROUND: More research is needed that compares the outcomes between those who underwent a hysterectomy for endometriosis with conservation of one or both ovaries and those who underwent a hysterectomy with bilateral salpingo-oophorectomy. OBJECTIVE: This study aimed to compare the rate and types of reoperations (primary outcome) and use of other pain-related health services (secondary outcomes) among people who underwent a hysterectomy with conservation of both ovaries, those who underwent a hysterectomy with unilateral salpingo-oophorectomy, and those who underwent a hysterectomy with bilateral salpingo-oophorectomy. STUDY DESIGN: This was a population-based, retrospective cohort study of 4489 patients aged 19 to 50 years in British Columbia, Canada, who underwent a hysterectomy for endometriosis between 2001 and 2016. Index surgeries were classified as hysterectomy alone (conservation of both ovaries), hysterectomy with unilateral salpingo-oophorectomy, or hysterectomy with bilateral salpingo-oophorectomy. Reoperation rate was the primary outcome. Secondary outcomes (measured at 3-12 months and 1-5 years after hysterectomy) included physician visits for endometriosis and pelvic pain, prescriptions filled for opioids, and use of hormonal suppression medications and hormone replacement therapy. RESULTS: Reoperation rates were low across all groups, with 89.5% of all patients remaining reoperation free by the end of follow-up (median of 10 years; interquartile range, 6.1-14.3 years). Patients who underwent a hysterectomy alone were more likely to undergo at least 1 reoperation when compared with those who underwent a hysterectomy with bilateral salpingo-oophorectomy (13% vs 5%; P<.0001), most commonly an oophorectomy or adhesiolysis. When oophorectomy as reoperation was removed in a sensitivity analysis, this difference was partially attenuated (6% of hysterectomy alone group vs 3% of hysterectomy with bilateral salpingo-oophorectomy group undergoing at least 1 reoperation). All groups were very similar in terms of rates of physician visits for endometriosis or pelvic pain and the number of days of opioid prescriptions filled. Furthermore, the rate of hormonal suppression medication use was similar among the groups, whereas the rate of prescriptions filled for hormone replacement therapy after hysterectomy with bilateral salpingo-oophorectomy was 60.6% of patients who filled at least 1 prescription at 3 to 12 months after index surgery. CONCLUSION: Patients who underwent a hysterectomy with bilateral salpingo-oophorectomy had a lower reoperation rate than those who underwent a hysterectomy with conservation of one or both ovaries. However, there was little difference between the groups for the secondary outcomes measured, including physician visits for endometriosis and pelvic pain, opioid use, and use of hormonal suppression medications, suggesting that persistent pelvic pain after hysterectomy for endometriosis may not differ substantively based on ovarian conservation status. One limitation was the inability to stratify patients by stage of endometriosis or to determine the impact of endometriosis stage or the presence of adnexal disease or deep endometriosis on the outcomes. Moreover, hormone replacement therapy prescriptions was not filled by about 40% of patients after hysterectomy with bilateral salpingo-oophorectomy, which may have significant health consequences for these individuals undergoing premature surgical menopause. Therefore, strong consideration should be given to ovarian conservation at the time of hysterectomy for endometriosis.

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention.

Individuals with proven hereditary cancer syndrome (HCS) such as BRCA1 and BRCA2 have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk. In response to this unmet opportunity for prevention, the British Columbia Gynecologic Cancer Initiative convened a research summit "Gynecologic Cancer Prevention: Thinking Big, Thinking Differently" in Vancouver, Canada on 26 November 2021. The aim of the conference was to explore how hereditary cancer prevention via population-based genetic testing could decrease morbidity and mortality from gynecologic cancer. The summit invited local, national, and international experts to (1) discuss how genetic testing could be more broadly implemented in a Canadian system, (2) identify key research priorities in this topic and (3) outline the core essential elements required for such a program to be successful. This report summarizes the findings from this research summit, describes the current state of hereditary genetic programs in Canada, and outlines incremental steps that can be taken to improve prevention for high-risk Canadians now while developing an organized population-based hereditary cancer strategy.

Bone health after RRBSO among BRCA1/2 mutation carriers: a population-based study.

OBJECTIVE: Examine the risks of fractures and osteoporosis after risk-reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA1/2 mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 to 2017, we compared risks of osteoporosis and fractures among women with BRCA1/2 mutations who underwent RRBSO before the age of 50 (n=329) with two age-matched groups without known mutations: 1) women who underwent bilateral oophorectomy (BO) (n=3,290); 2) women with intact ovaries who had hysterectomy or salpingectomy (n=3,290). Secondary outcomes were: having dual-energy X-ray absorptiometry (DEXA) scan, and bisphosphonates use. RESULTS: The mean age at RRBSO was 42.4 years (range, 26-49) and the median follow-up for women with BRCA1/2 mutations was 6.9 years (range, 1.1-19.9). There was no increased hazard of fractures for women with BRCA1/2 mutations (adjusted hazard ratio [aHR]=0.80; 95% confidence interval [CI]=0.56-1.14 compared to women who had BO; aHR=1.02; 95% CI=0.65-1.61 compared to women with intact ovaries). Among women who had DEXA-scan, those with BRCA1/2 mutations had higher risk of osteoporosis (aHR=1.60; 95% CI=1.00-2.54 compared to women who had BO; aHR=2.49; 95% CI=1.44-4.28 compared to women with intact ovaries). Women with BRCA1/2 mutations were more likely to get DEXA-scan than either control groups, but only 46% of them were screened. Of the women with BRCA1/2 mutations diagnosed with osteoporosis, 36% received bisphosphonates. CONCLUSION: Women with BRCA1/2 mutations had higher risk of osteoporosis after RRBSO, but were not at increased risk of fractures during our follow-up. Low rates of DEXA-scan and bisphosphonates use indicate we can improve prevention of bone loss.

Opportunistic salpingectomy between 2011 and 2016: a descriptive analysis.

BACKGROUND: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during hysterectomy for benign indications or instead of tubal ligation, for the purpose of preventing ovarian cancer. We determined rates of OS at the time of hysterectomy and tubal sterilization and examined how they changed over the study period. METHODS: Using data from the Canadian Institute for Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories (except Quebec) between the fiscal years 2011 and 2016, we conducted a descriptive analysis of all patients aged 15 years or older who underwent hysterectomy or tubal sterilization. We excluded those with diagnostic codes for any gynecologic cancer and those who underwent unilateral salpingectomy. We examined the proportion who had OS during their hysterectomy and compared the proportion of tubal sterilizations that were OS with the proportion that were tubal ligations. RESULTS: A total of 318 528 participants were included in the study (mean age 42.5 yr). The proportion of hysterectomies that included OS increased from 15.4% in 2011 to 35.5% by 2016. With respect to tubal sterilization, the rate of OS increased from 6.5% of all tubal sterilizations in 2011 to 22.0% in 2016. There was considerable variation across jurisdictions in 2016, with British Columbia having the highest rates (53.2% of all hysterectomies and 74.0% of tubal sterilizations involved OS). INTERPRETATION: The rates of OS increased between 2011 and 2016, but there was considerable variation across the included jurisdictions. Our study indicates room for rates of OS to increase across many of the included jurisdictions.

Outcomes From Opportunistic Salpingectomy for Ovarian Cancer Prevention.

Importance: Opportunistic salpingectomy (OS), which is the removal of fallopian tubes during hysterectomy or instead of tubal ligation without removal of ovaries, is recommended to prevent ovarian cancer, particularly serous ovarian cancer. However, the effectiveness of OS is still undetermined. Objective: To examine observed vs expected rates of ovarian cancer among individuals who have undergone OS. Design, Setting, and Participants: This is a population-based, retrospective cohort study of all individuals in British Columbia, Canada, who underwent OS or a control surgery (hysterectomy alone or tubal ligation) between 2008 and 2017, with follow-up until December 31, 2017. Those with any gynecological cancer diagnosed before or within 6 months of their procedure were excluded. Data analysis was performed from April to August 2021. Exposures: Removal of both fallopian tubes at the time of hysterectomy or instead of tubal ligation while leaving ovaries intact. Main Outcomes and Measures: An ovarian cancer diagnosis listed in the British Columbia Cancer Registry. Age-specific rates of epithelial and serous ovarian cancer in the control group were combined with the specific follow-up time in the OS group to calculate expected numbers (and 95% CIs) of ovarian cancers in the OS group. These were compared with observed numbers. Age-adjusted expected and observed numbers of breast and colorectal cancers were also examined in the OS group. Results: There were 25 889 individuals who underwent OS (mean [SD] age, 40.2 [7.1] years; median [IQR] follow-up, 3.2 [1.6-5.1] years) and 32 080 who underwent hysterectomy alone or tubal ligation (mean [SD] age, 38.2 [7.9] years; median [IQR] follow-up, 7.3 [4.6-8.7] years). There were no serous ovarian cancers in the OS group and 5 or fewer epithelial ovarian cancers. The age-adjusted expected number was 5.27 (95% CI, 1.78-19.29) serous cancers and 8.68 (95% CI, 3.36-26.58) epithelial ovarian cancers. Age-adjusted expected vs observed numbers of breast cancers (22.1 expected vs 23 observed) and colorectal cancers (9.35 expected vs 8 observed) were not significantly different. Conclusions and Relevance: In this cohort study, the OS group had significantly fewer serous and epithelial ovarian cancers than were expected according to the rate at which they arose in the control group. These findings suggest that OS is associated with reduced ovarian cancer risk.

Reproductive Factors Do Not Influence Survival with Ovarian Cancer.

BACKGROUND: Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small sample sizes. METHODS: Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype. RESULTS: During the mean follow-up of 6.34 years (SD = 4.80), 6,418 patients passed away (57.4%). There was no evidence of associations between the reproductive factors and survival among patients with ovarian cancer overall or by histotype. CONCLUSIONS: This study found no association between reproductive factors and survival after an ovarian cancer diagnosis. IMPACT: Reproductive factors are well-established risk factors for ovarian cancer, but they are not associated with survival after a diagnosis of ovarian cancer.

High Prediagnosis Inflammation-Related Risk Score Associated with Decreased Ovarian Cancer Survival.

BACKGROUND: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. METHODS: This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use; aspirin use; other nonsteroidal anti-inflammatory drug use; body mass index; environmental tobacco smoke exposure; history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis; menopausal hormone therapy use; physical inactivity; smoking status; and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data. RESULTS: There was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09; 95% confidence interval (CI), 1.03-1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11-1.54). CONCLUSIONS: A higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival. IMPACT: Given that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.

Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association.

OBJECTIVE: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. METHODS: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). CONCLUSIONS: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

Risk of cardiovascular disease among women carrying BRCA mutations after risk-reducing bilateral salpingo-oophorectomy: A population-based study.

OBJECTIVE: Examine the risk of cardiovascular disease (CVD) following risk reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 and 2017, we compared the risk of CVD among women with known BRCA mutations who underwent RRBSO before the age of 50 (n = 360) with two groups of age-matched women without known BRCA mutations: 1) women who underwent bilateral oophorectomy (BO) for benign conditions (n = 3600); and, 2) women with intact ovaries who had hysterectomy or salpingectomy (n = 3600). Our primary outcome was CVD (a composite (any of) myocardial infarction, heart failure, and/or cerebrovascular disease). Secondary outcomes included a diagnostic code for predisposing conditions (hypertension, dyslipidemia, and/or diabetes mellitus), and use of cardioprotective medications (statins and/or beta-blockers). RESULTS: We report no significant increased risk for CVD between women with BRCA mutations and women who underwent BO (aHR = 1.08, 95%CI: 0.72-1.62), but women with BRCA mutations were less likely to be diagnosed with predisposing conditions (aHR = 0.69, 95%CI: 0.55-0.85). Compared to women without BRCA mutations with intact ovaries who underwent hysterectomy or salpingectomy, women with BRCA mutations had significantly increased risk for CVD (aHR = 1.82, 95%CI: 1.18-2.79) and were less likely to be diagnosed with predisposing conditions (aHR = 0.78, 95%CI: 0.62-0.97) and to fill cardioprotective medications (aHR = 0.88, 95%CI: 0.64-1.22). CONCLUSION: Our results suggest an opportunity for improved prevention of CVD in women with BRCA mutations after prophylactic oophorectomy. Despite the observed lower prevalence of predisposing conditions for CVD and lesser use of cardioprotective medications, this population did not have a lower rate of CVD.