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

Abstract

IMPORTANCEMost 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.OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTSA 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.INTERVENTIONS 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. MAIN OUTCOMES AND MEASURESMenopause-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.RESULTS 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.CONCLUSIONS AND RELEVANCE 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.

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2

“…This demonstrated a better quality of life after risk-reducing salpingectomy irrespective of HRT. 71 Within the UK, the PROTECTOR study is evaluating the option of risk-reducing early salpingectomy with delayed oophorectomy in patients at high risk of OC. BRCA1, BRCA2, PALB2, BRIP1, RAD51C and RAD51D carriers are eligible for this study.…”

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk‐reducing surgery for hereditary breast and ovarian cancer

“…The results of the TUBA study, a non‐randomized multicenter clinical trial investigating RRSO and PSDO, has recently been published as well. The menopause‐related quality of life, which was the primary outcome of this study, was better in patients who have undergone risk‐reducing salpingectomy instead of RRSO 19 . However, oncologic safety of PSDO remains unclear 19 .…”

“…The menopause-related quality of life, which was the primary outcome of this study, was better in patients who have undergone risk-reducing salpingectomy instead of RRSO. 19 However, oncologic safety of PSDO remains unclear. 19 Currently, Japanese Guideline and NCCN guideline do not recommend PSDO in premenopausal women with gBRCA1/2 mutations because of the lack of evidence in oncologic safety after PSDO.…”

“…19 However, oncologic safety of PSDO remains unclear. 19 Currently, Japanese Guideline and NCCN guideline do not recommend PSDO in premenopausal women with gBRCA1/2 mutations because of the lack of evidence in oncologic safety after PSDO. 6,20 Discussion on Issues Surrounding RRSO in Japan Based on the above differences, issues surrounding RRSO in Japan shall be discussed.…”

The origins of ovarian cancer

“…The study that came out of those focus groups, known as the TUBA trial, enrolled 577 people with risk-gene mutations and offered them the choice of having their ovaries and fallopian tubes removed at once, or having a sequence of two operations: the first to remove the fallopian tubes and the second, by the age of 40-50, to take out the ovaries 10 .…”