Ovarian Cancer Risk Reduction Research Articles

Salpingectomy for the Risk Reduction of Ovarian Cancer: Is It Time for a Salpingectomy-alone Approach?

To summarize published evidence supporting current strategies for the prevention of epithelial ovarian cancer in women with a genetic, elevated risk for the development of this disease, as well as the emerging data on the novel salpingectomy with delayed oophorectomy (SDO) strategy. Furthermore, we will explore whether salpingectomy alone is a viable risk-reducing strategy for these women. We will also discuss current national guidelines for risk-reducing surgery based on patients' individual genetic predisposition. MEDLINE, PubMed, EMBASE, and the Cochrane Database, with a focus on randomized controlled trials and large prospective, observational studies. The key search terms for our review included Medical Subject Headings: "salpingectomy," "ovarian cancer," and "risk-reducing surgery." The fallopian tube is now well established as the site of origin for most ovarian cancers, particularly high-grade serous carcinomas. This finding has led to the development of new preventive surgical techniques, such as SDO, which may be associated with fewer side effects. However, until the results of ongoing trials are reported and the impact of SDO on ovarian cancer risk reduction is established, it should not be recommended outside of clinical trials, and bilateral salpingo-oophorectomy remains the treatment of choice for risk-reducing surgery, especially in women with a genetic, high risk for ovarian cancer. The decision to undergo risk-reducing surgery among women with an elevated risk for ovarian cancer should be made after comprehensive consultation and individually based on genetic predisposition, childbearing status, and personal preference.

Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies.

Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

Gynecologic Considerations for the Urologic Surgeon

While gynecologic malignancy is uncommon in women with conditions such as pelvic organ prolapse and bladder cancer, urologists should be acquainted with the relevant gynecologic literature as it pertains to their surgical care of female patients. While taking the patient history, urologists should be aware of prior cervical cancer screening and ask about vaginal bleeding, which can be a sign of uterine cancer. Urologic surgeons should also discuss the role of concomitant prophylactic oophorectomy and/or salpingectomy for ovarian cancer risk reduction at the time of pelvic surgery. An understanding of basic tests, such as a transvaginal sonogram, can help urologists provide comprehensive care.

V13-12 ADNEXAL MANAGEMENT AT THE TIME OF ELECTIVE PELVIC SURGERY IN WOMEN

You have accessJournal of UrologyFemale Pelvic Surgery (V13)1 Apr 2020V13-12 ADNEXAL MANAGEMENT AT THE TIME OF ELECTIVE PELVIC SURGERY IN WOMEN Adam Miller*, David Yang, and Brian Linder Adam Miller*Adam Miller* More articles by this author , David YangDavid Yang More articles by this author , and Brian LinderBrian Linder More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000970.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ovarian cancer has the highest mortality rate of all gynecologic cancers and is the fifth leading cause of cancer mortality in women with a lifetime risk of 1.4%. Despite advances in medicine, there has only been marginal improvement in survival over the past 50 years, mainly due to limited screening. It is known that many ovarian cancers are derived from the fallopian tube and not directly from the ovary. As such, opportunistic salpingectomy with or without oophorectomy has been proposed as a way to decrease ovarian cancer risk in patients undergoing routine pelvic surgery for other indications. The objective of our video is to discuss the role, feasibility, and surgical technique of opportunistic salpingectomy with or without oophorectomy for ovarian cancer risk reduction at the time of open, laparoscopic, or robotic pelvic surgery for another indication. METHODS: We present opportunistic salpingectomy and salpingo-oophorectomy in three patients. The first two cases highlight examples of this technique performed during robotic pelvic surgery and the third case is an example performed during open pelvic surgery. RESULTS: In our video, salpingectomy and salpingo-oophorectomy are performed with minimal added operative time or blood loss. No complications occurred due to the additional procedure. CONCLUSIONS: Salpingectomy and salpingo-oophorectomy for ovarian cancer risk reduction is a safe, feasible option for patients undergoing pelvic surgery. Surgeons familiar with operating in this location should consider opportunistic salpingectomy or salpingo-oophorectomy in females who are no longer interested in fertility preservation and who are undergoing routine pelvic surgery for another indication. Source of Funding: N/A © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1214-e1214 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adam Miller* More articles by this author David Yang More articles by this author Brian Linder More articles by this author Expand All Advertisement PDF downloadLoading ...

Prophylactic salpingectomy for the prevention of ovarian cancer: Who should we target?

Ovarian cancer is the most fatal gynecologic malignancy (50% 5-year survival) due to a typically advanced stage at diagnosis and a high rate of recurrence. Chemoprevention options are limited, and few interventions have been shown to reduce cancer risk or mortality. Emerging data support the model that fallopian tubes are the site of origin for a proportion of high-grade serous cancers. This implies that a subset of cancers may be prevented by removing the fallopian tubes while leaving the ovaries intact. Accordingly, there has been shift in clinical practice for average risk women; some now recommend removal of both the fallopian tubes only instead of tubal ligation for sterilization or at the time of benign gynecologic surgery. This has been termed opportunistic salpingectomy and represents a means of decreasing the burden of ovarian cancer by preventing cancers that arise in the fallopian tubes. There have been no detailed, prospective reports that have estimated ovarian cancer risk reduction with opportunistic salpingectomy, neither among women at baseline population risk nor among women at a high risk of developing the disease. The situation is complicated for women with a BRCA mutation-bilateral salpingo-oophorectomy is a proven means of risk reduction and salpingectomy alone is not the standard of care. Based on the existing data, salpingectomy alone should only be reserved for women with a lifetime risk of ovarian cancer of less than 5%.

Systematic review of acceptability, cardiovascular, neurological, bone health and HRT outcomes following risk reducing surgery in BRCA carriers.

Primary surgical prevention in the form of risk-reducing salpingo-oophorectomy (RRSO) is the most effective option and the gold standard for ovarian cancer (OC) risk-reduction, particularly given the absence of an effective national OC screening programme. However, premenopausal RRSO leads to premature surgical menopause with detrimental long-term health sequelae particularly in women who do not/are unable to take hormone replacement therapy (HRT). HRT uptake in women undergoing pre-menopausal oophorectomy appears low and is dependent on informed counselling, the safety of HRT and efficacy in mitigating the health sequelae of premature menopause. Acceptance of a central role for the fallopian tube in OC etiopathogenesis, coupled with the detrimental consequences of premature menopause, has led to the attractive proposal of early-salpingectomy with delayed oophorectomy as an alternative OC surgical prevention strategy in premenopausal women who have completed childbearing but decline or wish to delay RRSO. The successful implementation of risk reducing surgery for OC prevention depends on the acceptability of surgery to both, recipients (e.g. BRCA1/BRCA2 carriers) and intervention deliverers (healthcare professionals/researchers). Acceptability is also informed by an understanding of health outcomes following risk reducing surgery and the safety of HRT. It is therefore vital to understand the effects of surgery on important health outcomes such as cardiovascular health, neurological function and bone health. We present a comprehensive review of acceptability, the selected health outcomes mentioned above and HRT safety following risk reducing surgery.

Breast and ovarian cancer risk reduction options for women with pathogenic variables in the brca1 and brca2 genes

Introduction: Most breast and ovarian cancers in women are sporadic. However, five to ten percent of these individuals may have an inherited predisposition to cancer (Famorca-Tram, 2015). Women with pathogenic variants in BRCA1 are at risk of breast cancer of up to 72% and of ovarian cancer of up to 44%. Pathogenic variants of the BRCA2 gene increase the risk of breast cancer by up to 69% and of ovarian cancer by up to 25%. Risk reduction measures include: risk-reducing mastectomy, salpingo-oophorectomy, and chemoprevention. For women who do not choose any of these measures, follow-up with periodic examinations is necessary. In this work, the risk reduction measures adopted by 52 women with pathogenic variants in BRCA1 or BRCA2 in a tertiary hospital in São Paulo, Brazil, are analyzed. In addition, it was analyzed what factors could influence the risk-reducing measure adopted. Materials and methods: cross-sectional study with a sample of 52 women with pathogenic variants identified in the BRCA1 and BRCA2 genes seen at a tertiary hospital. Results: 80.8% opted for surgical management as a risk-reducing measure, with 46.2% of women having had prophylactic mastectomy, 11.5% having had bilateral salpingo-oophorectomy, and 23.1% having undergone both surgical procedures. Non-surgical management occurred in 19.2% of the cases, with 8% (3 cases) undergoing chemoprophylaxis with tamoxifen and 15.4% undergoing surveillance. Conclusion: Most patients opted for surgical intervention, with risk-reducing mastectomy being the most frequent one, followed by salpingo-oophorectomy. When testing was not requested by the geneticist, there was a greater tendency toward the surgical option.

Completeness of salpingectomy intended for ovarian cancer risk reduction

BackgroundProphylactic salpingectomy has been heavily promoted based on the theory that serous tubal intraepithelial carcinoma is a precursor lesion for serous ovarian carcinoma. However, the validity of prophylactic salpingectomy has yet to be proven through adequate research. The purpose of this study is to evaluate the completeness of salpingectomy intended for ovarian cancer risk reduction. Materials and methodsWomen without a history of ovarian cancer who were undergoing salpingoophorectomy at a single institution in Honolulu, Hawaii were enrolled in this study. Salpingectomy was performed prior to oophorectomy. A blinded pathologist then examined the ovaries for the presence of residual salpingeal tissue. Data collected included type of surgery (minimally invasive or laparotomy) and level of surgeon (attending or resident). Data were analyzed using Fisher's exact test. ResultsA total of 107 ovaries were examined. Following salpingectomy, 5.6% (n = 6/107) of ovaries had residual salpingeal tissue present and 94.4% (n = 101/107) of ovaries were absent of salpingeal tissue. Of the ovaries with residual salpingeal tissue, there was no difference in level of surgeon (attending n = 3/107, resident n = 3/107, p = 1.0) or type of surgery (minimally invasive n = 5/107, laparotomy n = 1/107, p = 0.42). DiscussionThis is the largest blinded study ever conducted to examine ovaries for residual salpingeal tissue after salpingectomy. In addition, this is the only study to compare learner versus attending outcomes in this setting. This study found that over 94% of salpingectomies resulted in complete removal of salpingeal tissue. Of the ovaries with residual salpingeal tissue, there wasn't a difference among surgeon level and surgery type, but the study was not powered to detect this. This study supports the continued clinical practice of prophylactic salpingectomy for ovarian cancer risk reduction.

Opportunistic Salpingectomy at the Time of Urogynecologic Surgery: Why, in Whom, and How?

This review aims to (1) describe evidence supporting the fallopian tube as a site of high-grade serous carcinoma, (2) review literature regarding salpingectomy in high- and average-risk women, and (3) discuss feasibility and safety of salpingectomy in urogynecologic surgery. PubMed and university library resources were used to retrieve relevant English-language publications via keyword search, including "ovarian cancer," "salpingectomy," "risk," "safety," "hysterectomy," "trends," "technique," and "urogynecology." Each publication was reviewed in detail and references incorporated, where relevant. Evidence supports the fimbriated portion of the fallopian tube as a site of high-grade serous carcinoma in both hereditary and sporadic cases. Routine opportunistic salpingectomy in average-risk women may reduce ovarian cancer risk by 42% to 65% and prevent future surgery for benign tubal disease. Opportunistic salpingectomy is cost-effective for sterilization and cost-saving during hysterectomy. For genetically predisposed women, salpingo-oophorectomy remains the recommended strategy for ovarian cancer risk reduction. Despite being feasible, safe, and cost-effective, concomitant salpingectomy is least commonly performed during vaginal hysterectomy compared with other hysterectomy routes. Salpingectomy rates during vaginal hysterectomy are influenced by geographic factors, surgeon experience, and adhesive disease. Opportunistic salpingectomy holds promise as a risk-reducing intervention for ovarian cancer. The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncology recommend that physicians counsel average-risk women regarding opportunistic salpingectomy when planning pelvic surgery. Randomized controlled trials are needed to evaluate long-term implications of salpingectomy. Urogynecologic surgeons should discuss salpingectomy as part of surgical informed consent. Vaginal salpingectomy should be incorporated into residency and fellowship training programs.

Breastfeeding: Investing in the Future.

Breastfeeding: Investing in the Future.

The Association Between Hysterectomy and Ovarian Cancer Risk: A Population-Based Record-Linkage Study.

Recent studies have called into question the long-held belief that hysterectomy without oophorectomy protects against ovarian cancer. This population-based longitudinal record-linkage study aimed to explore this relationship, overall and by age at hysterectomy, time period, surgery type, and indication for hysterectomy. We followed the female adult Western Australian population (837 942 women) across a 27-year period using linked electoral, hospital, births, deaths, and cancer records. Surgery dates were determined from hospital records, and ovarian cancer diagnoses (n = 1640) were ascertained from cancer registry records. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer incidence. Hysterectomy without oophorectomy (n = 78 594) was not associated with risk of invasive ovarian cancer overall (HR = 0.98, 95% CI = 0.85 to 1.11) or with the most common serous subtype (HR = 1.05, 95% CI = 0.89 to 1.23). Estimates did not vary statistically significantly by age at procedure, time period, or surgical approach. However, among women with endometriosis (5.8%) or with fibroids (5.7%), hysterectomy was associated with substantially decreased ovarian cancer risk overall (HR = 0.17, 95% CI = 0.12 to 0.24, and HR = 0.27, 95% CI = 0.20 to 0.36, respectively) and across all subtypes. Our results suggest that for most women, having a hysterectomy with ovarian conservation is not likely to substantially alter their risk of developing ovarian cancer. However, our results, if confirmed, suggest that ovarian cancer risk reduction could be considered as a possible benefit of hysterectomy when making decisions about surgical management of endometriosis or fibroids.

Factors influencing decision-making around opportunistic salpingectomy: a nationwide survey.

ObjectiveTo explore current practice and influencing factors on adoption of the opportunistic salpingectomy (OS), particularly regarding the decision making, to eventually enhance the development and implementation of clear guidelines.MethodsThis nationwide cross-sectional survey study was conducted in all hospitals in the Netherlands. An anonymous online survey was sent to gynecologists with special interest in gynecological oncology, gynecological endoscopy or urogynecology and all Dutch gynecology trainees. The survey mainly focused on current practice regarding OS and identification of influencing factors on the level of innovation, organization, healthcare professional and individual patient.ResultsThe response rate was 348 out of 597 gynecologists (58.3%) and 142 out of 340 trainees (41.8%). Current practice of discussing and performing the OS varied widely, with ovarian cancer (OC) risk reduction as most important supportive factor on innovation level. Supportive factors on the level of organization and healthcare provider were; working in a non-training hospital, knowledge of current literature and extensive work experience (in years and annual number of hysterectomies). On individual patient level, a vaginal approach of hysterectomy, negative family history for OC and the presence of firm adhesions were suppressive factors for the OS.ConclusionIn this study we evaluated the current practice regarding the opportunistic salpingectomy in the Netherlands and identified influencing factors on different levels to raise awareness and attribute to development of a targeted implementation strategy, on both national and international level.

The cost-effectiveness of opportunistic salpingectomy versus standard tubal ligation at the time of cesarean delivery for ovarian cancer risk reduction

ObjectivesOpportunistic salpingectomy is a cost-effective strategy recommended for ovarian cancer (OvCa) risk reduction at the time of gynecologic surgery in women who have completed childbearing. We aimed to evaluate the cost-effectiveness of opportunistic salpingectomy compared to standard tubal ligation (TL) during cesarean delivery. Study designA cost-effectiveness analysis using decision modeling to compare opportunistic salpingectomy to TL at the time of cesarean using probabilities of procedure completion derived from a trial. Probability and cost inputs were derived from local data and the literature. The primary outcome was the incremental cost-effectiveness ratio (ICER) in 2017 U.S. dollars per quality-adjusted life year (QALY) at a cost-effectiveness threshold of $100,000/QALY. One- and two-way sensitivity analyses were performed for all variables. A probabilistic sensitivity analysis determined the proportion of simulations in which each strategy would be cost-effective. ResultsOpportunistic salpingectomy was cost-effective compared to TL with an ICER of $26,616 per QALY. In 10,000 women desiring sterilization with cesarean, opportunistic salpingectomy would result in 17 fewer OvCa diagnoses, 13 fewer OvCa deaths, and 25 fewer unintended pregnancies compared to TL – with an associated cost increase of $4.7 million. The model was sensitive only to OvCa risk reduction from salpingectomy and TL. Opportunistic salpingectomy was not cost-effective if its cost was >$3163.74 more than TL, if the risk-reduction of salpingectomy was <41%, or if the risk-reduction of TL was >46%. In probabilistic sensitivity analysis opportunistic salpingectomy was cost effective in 75% of simulations. ConclusionsIn women undergoing cesarean with sterilization, opportunistic salpingectomy is likely cost-effective and may be cost-saving in comparison to TL for OvCa risk reduction.

Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study

ObjectivesTo investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer.DesignProspective, nationwide cohort study.SettingDenmark,...

Cost-effectiveness of opportunistic salpingectomy vs tubal ligation at the time of cesarean delivery

Removal of the fallopian tubes at the time of hysterectomy or interval sterilization has become routine practice to prevent ovarian cancer. While emerging as a strategy, uptake of this procedure at the time of cesarean delivery for pregnant women seeking permanent sterilization has not been widely adopted due to perceptions of increased morbidity and operative difficulty with a lack of available data in this setting. We sought to conduct a cost-effectiveness analysis comparing strategies for long-term sterilization and ovarian cancer risk reduction at the time of cesarean delivery, including bilateral tubal ligation, opportunistic salpingectomy, and long-acting reversible contraception. A decision-analytic and cost-effectiveness model was constructed for pregnant women undergoing cesarean delivery who desired permanent sterilization in the US population, comparing 3 strategies: (1) bilateral tubal ligation, (2) bilateral opportunistic salpingectomy, and (3) postpartum long-acting reversible contraception. This theoretic cohort consisted of 110,000 pregnant women desiring permanent sterilization at the time of cesarean delivery and ovarian cancer prevention at an average of 35 years who were monitored for an additional 40 years based on an average US female life expectancy of 75 years. The primaryoutcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured as quality-adjusted life years. Secondary outcomes included: the number of ovarian cancer cases and deaths, procedure-related complications, and unintended and ectopic pregnancies. The 1-, 2-, and 3-way and Monte Carlo probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set at $100,000. Both bilateral tubal ligation and bilateral opportunistic salpingectomy with cesarean delivery have favorable cost-effectiveness ratios. In the base case analysis, salpingectomy was more cost-effective with an incremental cost-effectiveness ratio of $23,189 per quality-adjusted life year compared to tubal ligation. Long-acting reversible contraception after cesarean was not cost-effective (ie, dominated). Although salpingectomy and tubal ligation were both cost-effective over a wide range of cost and risk estimates, the incremental cost-effectiveness ratio analysis was highly sensitive to the uncertainty around the estimates of salpingectomy cancer risk reduction, risk of perioperative complications, and cost. Monte Carlo probabilistic sensitivity analysis estimated that tubal ligation had a 49% chance of being the preferred strategy over salpingectomy. If the true salpingectomy risk of perioperative complications is >2% higher than tubal ligation or if the cancer risk reduction of salpingectomy is <52%, then tubal ligation is the preferred, more cost-effective strategy. Bilateral tubal ligation and bilateral opportunistic salpingectomy with cesarean delivery are both cost-effective strategies for permanent sterilization and ovarian cancer risk reduction. Although salpingectomy and tubal ligation are both reasonable strategies for cesarean patients seeking permanent sterilization and cancer risk reduction, threshold analyses indicate that the risks and benefits of salpingectomy with cesarean delivery need to be better defined before a preferred strategy can be determined.

Abstract 4942: Serologic markers of infectious agents and ovarian cancer: Markers of prior Chlamydia trachomatis infection associated with increased ovarian cancer risk in two independent populations

Abstract Background: Pelvic inflammatory disease (PID) has been associated with ovarian cancer and Chlamydia trachomatis (chlamydia) is the leading cause of PID in the developed world. Primary infection with chlamydia is often asymptomatic and may persist for several months/years, thus ascertainment of PID in epidemiologic studies is challenging due to pervasive misclassification and under-reporting. To improve our understanding of the role of chlamydia and other infectious agents in developing ovarian cancer, we evaluated serologic markers of infection with incident ovarian cancer using a staged approach in two independent populations. Methods: Studies included: 1) a case-control study conducted in Poland of 278 ovarian cancer cases diagnosed from 2000 to 2003 and age- and study site-matched controls (n=556) and 2) a nested case-control study from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial including 160 women who eventually developed ovarian cancer and 159 matched controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between serologic marker titers and ovarian cancer risk using logistic regression adjusted for matching factors and potential confounders. We evaluated laboratory cutpoints indicative of prior chlamydia infection and tested more stringent marker thresholds, identified in Poland and applied in PLCO, that could be relevant for a PID-like infection. Results: In the Polish study, positivity for the chlamydia plasmid-encoded Pgp3 protein was associated with increased ovarian cancer risk [OR (95% CI): 1.63 (1.20-2.22)]; when a positive result was redefined at a higher titer, ovarian cancer risk increased [cutpoint 2: 2.00 (1.38-2.89); cutpoint 3 (max OR): 2.19 (1.29-3.73)]. All other chlamydia markers measured were associated with increased risk at the more stringent positivity threshold in Poland. In the prospective PLCO study, Pgp3 was associated with elevated risk at the laboratory cutpoint [1.43 (0.78-2.63)]; using higher thresholds, Pgp3 was associated with increased ovarian cancer risk [cutpoint 2: 2.25 (1.07-4.71); cutpoint 3: 2.53 (0.63-10.08)]. In both studies, markers of other infections (i.e., Mycoplasma genitalium, herpes simplex virus-2, human papillomavirus, herpes simplex virus-1, polyomavirus, hepatitis B, hepatitis C, Epstein Barr virus, cytomegalovirus) measured were not associated with risk. Conclusions: In two independent populations, the gold standard serologic marker of prior/current chlamydia infection (Pgp3) was associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. Although these findings need to be replicated, they suggest potential ovarian cancer risk reduction through targeted treatment of chlamydia infections. Citation Format: Britton Trabert, Tim Waterboer, Sally B. Coburn, Louise A. Brinton, Mark E. Sherman, Jolanta Lissowska, Beata Peplonska, Patricia Hartge, Michael Pawlita, Nicolas Wentzensen. Serologic markers of infectious agents and ovarian cancer: Markers of prior Chlamydia trachomatis infection associated with increased ovarian cancer risk in two independent populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4942.

Risk reduction of endometrial and ovarian cancer after bisphosphonates use: A meta-analysis

ObjectiveRecent epidemiological studies have investigated the associations between the use of bisphosphonates and the development of endometrial cancer and ovarian cancer; these studies have shown controversial results. Hence, this meta-analysis was conducted to evaluate the changes in the risks of developing endometrial and ovarian cancers after using bisphosphonates based on current evidence. MethodsA comprehensive search was performed in the MEDLINE, EMBASE, and Web of Science databases through January 2017. The summary relative risk (RR) estimates for the effects of the use of bisphosphonates on the risks of developing endometrial and ovarian cancers were calculated using a random-effects model. ResultsSeven studies were included with a total of 6471 endometrial cancer cases (7 studies with 213,920 participants) and 6783 ovarian cancer cases (4 studies with 105,507 participants). This meta-analysis suggested that any use of bisphosphonates was associated with a significant 27% reduction in the risk of endometrial cancer (RR = 0.73, 95% CI: 0.58–0.93, P = 0.012), but the reduction in the risk of ovarian cancer (RR = 0.81, 95% CI: 0.58–1.14, P = 0.227) was not significant. The protective effects of the use of bisphosphonates against endometrial cancer are mainly found in postmenopausal women (RR = 0.53, 95% CI: 0.34–0.93, P = 0.012) or in those who have taken bisphosphonates for longer than 1 year (RR = 0.57, 95% CI: 0.35–0.93, P = 0.024). ConclusionThis meta-analysis suggests that the use of bisphosphonates is associated with a reduction in the risk of endometrial cancer but not ovarian cancer.

Analgesic Use and Ovarian Cancer Risk: An Analysis in the Ovarian Cancer Cohort Consortium.

Aspirin use is associated with reduced risk of several cancers. A pooled analysis of 12 case-control studies showed a 10% decrease in ovarian cancer risk with regular aspirin use, which was stronger for daily and low-dose users. To prospectively investigate associations of analgesic use with ovarian cancer, we analyzed data from 13 studies in the Ovarian Cancer Cohort Consortium (OC3). The current study included 758 829 women who at study enrollment self-reported analgesic use, among whom 3514 developed ovarian cancer. Using Cox regression, we assessed associations between frequent medication use and risk of ovarian cancer. Dose and duration were also evaluated. All statistical tests were two-sided. Women who used aspirin almost daily (≥6 days/wk) vs infrequent/nonuse experienced a 10% reduction in ovarian cancer risk (rate ratio [RR] = 0.90, 95% confidence interval [CI] = 0.82 to 1.00, P = .05). Frequent use (≥4 days/wk) of aspirin (RR = 0.95, 95% CI = 0.88 to 1.03), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; RR = 1.00, 95% CI = 0.90 to 1.11), or acetaminophen (RR = 1.05, 95% CI = 0.88 to 1.24) was not associated with risk. Daily acetaminophen use (RR = 1.28, 95% CI = 1.00 to 1.65, P = .05) was associated with elevated ovarian cancer risk. Risk estimates for frequent, long-term (10+ years) use of aspirin (RR = 1.15, 95% CI = 0.98 to 1.34) or nonaspirin NSAIDs (RR = 1.19, 95% CI = 0.84 to 1.68) were modestly elevated, although not statistically significantly so. This large, prospective analysis suggests that women who use aspirin daily have a slightly lower risk of developing ovarian cancer (∼10% lower than infrequent/nonuse)-similar to the risk reduction observed in case-control analyses. The observed potential elevated risks for 10+ years of frequent aspirin and NSAID use require further study but could be due to confounding by medical indications for use or variation in drug dosing.

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations

ObjectiveRisk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. MethodsIn this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. ResultsOf the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P < 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses. ConclusionsIn this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

Breastfeeding is associated with the risk of ovarian cancer in the UK Women's Cohort Study

Studies have found that longer breastfeeding duration is associated with the risk of having ovarian cancer and other hormonal related cancers(1). However, the evidence is still inconsistent with a limited number of prospective studies providing evidence(2). Therefore, this analysis aimed to explore the association between breastfeeding duration and the risks of ovarian cancer in a large prospective cohort of middle-aged women, the UK Women’s Cohort Study (UKWCS). The UKWCS participants were recruited in 1995–1998 at the age of 35–69 years(3). Cancer incidence was obtained from the Office of National Statistics (ONS). A baseline questionnaire was used to estimate breastfeeding duration, ranging from >0 months to >6 months. Patients with prevalent cancers were excluded. The relationship between breast feeding duration and incidence of ovarian cancer was tested using survival analysis adjusting for age, children, socio-economic class, menopausal status, smoking status, body mass index, energy intake and age at menarche. The total number of incident ovarian cancer cases was 224 over 16 years follow up. Mean age at recruitment was 54 years. Breastfeeding duration for each child shows that ever breastfeeding was associated with 6 % risk reduction of ovarian cancer, after adjustment for confounders (HR: 0·94; 95 % CI: 0·90 to 0·99). Further analysis on breastfeeding duration per child shows that the risk reduces by 43 % among those who breastfed for more than 6 months per child (HR: 0·57; 95 % CI: 0·35 to 0·95). Additional analysis was done on cumulative breastfeeding duration across all children, with ovarian cancer risk, which shows a 2 % risk reduction for every 1 month of breastfeeding (HR: 0·98; 95 % CI: 0·97 to 1·00). In conclusion, ever breastfeeding per child was associated with 6 % risk reduction of ovarian cancer in a fully adjusted model and those who were breastfeeding for more than 6-month benefit more with a high-risk reduction of ovarian cancer by 43 %. This finding supports the World Health Organisation (WHO) recommendation for women to breastfeed for at least 6 months for each child. Future studies are warranted to determine if the duration of breastfeeding per child provides more meaningful data than cumulative breastfeeding duration. The average duration of breastfeeding per child might have more public health applicability than total duration and is a better reflection of lactation amenorrhea(1). 1. Luan NN, Wu QJ, Gong TT et al. (2013) Breastfeeding and ovarian cancer risk: a meta-analysis of epidemiologic studies.AmJ Clin Nutr 98, 1020–31. 2. Feng LP, Chen HL & Shen MY (2014) Breastfeeding and the risk of ovarian cancer: a meta-analysis. J Midwifery Womens Health 59, 428–37. 3. Cade JE, Burley VJ, Alwan NA et al. (2017) Cohort Profile: The UK Women’s Cohort Study (UKWCS). Int J Epidemiol 46, e11.