Tamar A Gootzen

Impact of breast cancer history on decision-making for ovarian cancer risk-reducing surgery in the TUBA-WISP-II study

Female BRCA1/2 pathogenic variant carriers have an increased risk of breast and ovarian cancer. In the TUBA-WISP II study, women chose between standard risk-reducing salpingo-oophorectomy and risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer. At inclusion, a substantial proportion of the enrolled women had a history of breast cancer, which could affect decision-making. This study aimed to describe decision-making regarding the type and timing of risk-reducing surgery between women with and without a history of breast cancer. Premenopausal BRCA1/2 pathogenic variant carriers completed Web-based questionnaires on their personal histories and preferred risk-reducing strategy. Differences in the type and timing of the first risk-reducing surgery between women with and without a history of breast cancer were assessed. A multivariate analysis was performed to examine personal, environmental, and breast cancer-related characteristics associated with the choice of risk-reducing salpingo-oophorectomy among women with a history of breast cancer. This study included 1676 women, among whom 222 (13.2%) had a history of breast cancer. Of note, 77.0% of women with a history of breast cancer chose risk-reducing salpingectomy with delayed oophorectomy compared with 78.0% of women without a history of breast cancer (P=.73). Individuals with breast cancer before their BRCA1/2 diagnosis had their first surgery at a median of 2 years later than those who were diagnosed simultaneously or had their BRCA1/2 diagnosis first. Women diagnosed with breast cancer within the guideline age range for completing risk-reducing salpingo-oophorectomy (35-40 years for BRCA1 and 40-45 years for BRCA2) more often chose risk-reducing salpingo-oophorectomy than those before the guideline age range (odds ratio, 6.2 [95% confidence interval, 1.9-19.9]). A history of breast cancer was not associated with a preference for a specific risk-reducing strategy. Women diagnosed with breast cancer within the guideline age range more often chose risk-reducing salpingo-oophorectomy than those diagnosed with breast cancer before the guideline age range.

Pathogenesis of peritoneal high‐grade serous carcinoma after risk‐reducing surgery: a systematic review

AbstractGermline BRCA1/2 pathogenic variant carriers have an increased risk for high‐grade serous carcinoma (HGSC) and are therefore advised to have risk‐reducing salpingo‐oophorectomy around the age of 40. However, a risk of 0.9% to develop peritoneal HGSC remains in these women, which increases to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected. The pathophysiological mechanism that leads to the development of peritoneal HGSC after salpingectomy or salpingo‐oophorectomy is still largely unknown. In this systematic review, we aim to provide insights into the pathogenic pathways of peritoneal HGSC after salpingectomy or salpingo‐oophorectomy. Therefore, we performed a systematic search for studies investigating pathophysiological mechanisms related to peritoneal HGSC in PubMed and EMBASE. A total of 49 articles were included in this study. Most evidence was found on mechanisms following a tubal origin, such as clonality between STIC and peritoneal HGSC as well as molecular similarities between fallopian tube (FT) epithelium and peritoneal HGSC. Additionally, FT epithelium was shown to adhere to the ovary and could therefore stay present after isolated salpingectomy. There might be a role for the endometrium, as it was observed that serous endometrial intraepithelial carcinoma (SEIC) has a clonal relationship with extra‐uterine HGSC. The role of the ovary seems limited, although some mouse models show a role for follicular fluid in the dissemination of malignant cells on the peritoneum. In conclusion, different mechanisms might be responsible for peritoneal HGSC development after bilateral salpingectomy or salpingo‐oophorectomy. Most available evidence supports the dissemination of precursor cells originating in the FT. Also, a possible role for the endometrium was found. An ovarian origin seems less likely; however, execution of oophorectomy does not seem obsolete in clinical practice as follicular fluid might promote dissemination and residual tubal tissue can be present on the ovary after salpingectomy.

Opportunistic Salpingectomy in Non‐Gynecologic Surgeries: Barriers and Facilitators From a Healthcare Provider Perspective

ABSTRACT Objective This study identifies barriers and facilitators for implementing opportunistic salpingectomy (OS) during non‐gynecological abdominal surgeries from a healthcare provider perspective. Methods From October 2023 to July 2024, a mixed‐method study was conducted. The qualitative phase involved semi‐structured focus group interviews and individual interviews with specialists in surgery (gynecologists, general surgeons, urologists, and residents) and policymakers to identify barriers and facilitators for implementing OS during non‐gynecological surgery. The quantitative phase consisted of a cross‐sectional web‐based survey assessing the importance of these barriers and facilitators. The study utilized the standardized implementation frameworks to categorize the factors into six domains: innovation, patient, healthcare professional, social setting, organization, and economic and financial context. Results In the qualitative phase, 38 healthcare professionals and policymakers identified 38 barriers and 28 facilitators. Barriers were found in all domains and mainly included increased workload, unclear invoicing, and variations in eligible surgeries. Facilitators included the poor prognosis of ovarian cancer, simplicity of OS, and availability of counseling materials. The quantitative survey revealed that 75% of gynecologists, 60% of surgeons, and 61% of urologists supported offering OS during non‐gynecological abdominal surgeries. Barriers identified included the ambiguity regarding which patients are eligible for OS, the perceived complication risks of OS, the increased workload as a result of adding OS, and the unclarity around invoicing an OS. Facilitators included the poor prognosis of ovarian cancer, the availability of uniform counseling materials, education on counseling and technical performance of OS, involvement of a gynecologist during the counseling, and clear agreements between the departments within hospitals. Conclusions Key barriers to OS implementation in non‐gynecological surgeries include unclear invoicing and increased workload, while significant facilitators are the availability of counseling materials and education on counseling and technical performance of OS. Addressing these barriers and leveraging facilitators could enhance OS adoption, potentially reducing ovarian cancer incidence.

Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy

AbstractEpithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms. Women with an increased inherited risk for EOC are advised to undergo a risk-reducing salpingo-oophorectomy (RRSO), which decreases their EOC risk by 96% when performed within guideline ages. However, it also induces premature menopause, which has harmful consequences. There is compelling evidence that the majority of EOCs originate in the fallopian tube. Therefore, a risk-reducing salpingectomy with delayed oophorectomy (RRS with DO) has gained interest as an alternative strategy. Previous studies have shown that this alternative strategy has a positive effect on menopause-related quality of life and sexual health when compared to the standard RRSO. It is hypothesized that the alternative strategy is non-inferior to the standard RRSO with respect to oncological safety (EOC incidence). Three prospective studies are currently including patients to compare the safety and/or quality of life of the two distinct strategies. In this article we discuss the background, opportunities, and challenges of the current and alternative strategy.