Early Salpingectomy (Tubectomy) With Delayed Oophorectomy in BRCA1/2 Gene Mutation Carriers

Development of cardiovascular risk factors in women with a BRCA1/2 pathogenic variant within five years after tubo-ovarian cancer risk reduction in the TUBA study

The effects of risk-reducing salpingo-oophorectomy on the development of cardiovascular risk factors in women with BRCA1/2 pathogenic variants are unknown. We compared the development of cardiovascular risk factors 5 years post-surgery between participants who had risk-reducing salpingo-oophorectomy with and without hormonal replacement therapy and participants who had risk-reducing salpingectomy. Eligible participants with a BRCA1/2 pathogenic variant from the TUBA study were longitudinally followed and categorized into three groups: (1) salpingectomy without subsequent oophorectomy within 5 years, (2) salpingo-oophorectomy with hormonal replacement therapy (use ≥3 years), (3) salpingo-oophorectomy without hormonal replacement therapy (use <3 years). Development of cardiovascular risk factors between baseline and 5 years after salpingo-oophorectomy or salpingectomy. Of the 400 participants, 258 (64.5%) had salpingectomy, 93 (23.3%) had salpingo-oophorectomy and used hormonal replacement therapy ≥3 years, and 49 (12.2%) used it for <3 years. At 5-year follow-up, the cardiovascular risk factor hypercholesterolemia (increased LDLc) was observed more often after salpingo-oophorectomy with (18.8%, p ≤0.001) and without (17.1%, p = 0.03) hormonal replacement therapy compared with the salpingectomy group (5.7%). Larger proportions of participants after salpingo-oophorectomy with (47.1%) and without (50.0%) hormonal replacement therapy experienced an increase in the number of risk factors present compared with participants after salpingectomy (24.5%; p = 0.009, p = 0.02, respectively). Overall, only a small proportion of the study population developed cardiovascular risk factors within five years after salpingo-oophorectomy. However, participants developed the risk factor hypercholesterolemia more after salpingo-oophorectomy (irrespective of use of hormonal replacement therapy) compared with after salpingectomy. NCT02321228.

Cancer worry among BRCA1/2 pathogenic variant carriers choosing surgery to prevent tubal/ovarian cancer: course over time and associated factors

Abstract Objective High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers undergoing surgery to prevent ovarian cancer, and identified factors associated with high cancer worry. Methods Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose either novel risk-reducing salpingectomy with delayed oophorectomy or standard risk-reducing salpingo-oophorectomy. The Cancer Worry Scale was obtained before and 3 and 12 months after surgery. Cancer worry patterns were analysed using latent class growth analysis and associated factors were identified with regression analysis. Results Of all 577 BRCA1/2-PV carriers, 320 (57%) had high (≥ 14) cancer worry pre-surgery, and 54% had lower worry 12 months post-surgery than pre-surgery. Based on patterns over time, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56%), persistently high cancer worry (6%), and fluctuating, mostly declining, cancer worry (37%). Factors associated with persistently high cancer concerns were age below 35 (BRCA1) or 40 (BRCA2), unemployment, previous breast cancer, lower education and a more recent BRCA1/2-PV diagnosis. Conclusions Some degree of cancer worry is considered normal, and most BRCA1/2-PV carriers have declining cancer worry after gynaecological risk-reducing surgery. However, a subset of these BRCA1/2-PV carriers has persisting major cancer concerns up to 1 year after surgery. They should be identified and potentially offered additional support. Clinical trial registration The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number: NCT02321228.

Association of Salpingectomy With Delayed Oophorectomy Versus Salpingo-oophorectomy With Quality of Life in BRCA1/2 Pathogenic Variant Carriers

Most women with a BRCA1/2 pathogenic variant undergo premature menopause with potential short- and long-term morbidity due to the current method of ovarian carcinoma prevention: risk-reducing salpingo-oophorectomy (RRSO). Because the fallopian tubes play a key role in ovarian cancer pathogenesis, salpingectomy with delayed oophorectomy may be a novel risk-reducing strategy with benefits of delaying menopause. To compare menopause-related quality of life after risk-reducing salpingectomy (RRS) with delayed oophorectomy with RRSO in carriers of the BRCA1/2 pathogenic variant. A multicenter nonrandomized controlled preference trial (TUBA study), with patient recruitment between January 16, 2015, and November 7, 2019, and follow-up at 3 and 12 months after surgery was conducted in all Dutch university hospitals and a few large general hospitals. In the Netherlands, RRSO is predominantly performed in these hospitals. Patients at the clinical genetics or gynecology department between the ages of 25 and 40 years (BRCA1) or 25 to 45 years (BRCA2) who were premenopausal, had completed childbearing, and were undergoing no current treatment for cancer were eligible. Risk-reducing salpingo-oophorectomy at currently recommended age or RRS after completed childbearing with delayed oophorectomy. After RRSO was performed, hormone replacement therapy was recommended for women without contraindications. Menopause-related quality of life as assessed by the Greene Climacteric Scale, with a higher scale sum (range, 0-63) representing more climacteric symptoms. Secondary outcomes were health-related quality of life, sexual functioning and distress, cancer worry, decisional regret, and surgical outcomes. A total of 577 women (mean [SD] age, 37.2 [3.5] years) were enrolled: 297 (51.5%) were pathogenic BRCA1 variant carriers and 280 (48.5%) were BRCA2 pathogenic variant carriers. At the time of analysis, 394 patients had undergone RRS and 154 had undergone RRSO. Without hormone replacement therapy, the adjusted mean increase from the baseline score on the Greene Climacteric Scale was 6.7 (95% CI, 5.0-8.4; P < .001) points higher during 1 year after RRSO than after RRS. After RRSO with hormone replacement therapy, the difference was 3.6 points (95% CI, 2.3-4.8; P < .001) compared with RRS. Results of this nonrandomized controlled trial suggest that patients have better menopause-related quality of life after RRS than after RRSO, regardless of hormone replacement therapy. An international follow-up study is currently evaluating the oncologic safety of this therapy. ClinicalTrials.gov Identifier: NCT02321228.

Majke van Bommel