Research Themes Womens cancers Introduction risk reducing salpingectomy for prevention of ovarian cancer
Epithelial ovarian cancer is the most lethal malignancy of the female genital tract. Women with germline mutations in one of the two BRCA genes are at increased risk of developing ovarian cancer. Cumulative ovarian cancer risks are approx. 39–40 % and 11–18 % for BRCA1 and BRCA2, respectively. In contrast to breast cancer surveillance, screening for ovarian cancer has not been effective. Therefore, the only intervention to reduce ovarian cancer risk has been a risk reducing salpingo-oophorectomy (RRSO), which decreases ovarian cancer incidence by about 80–96 %. Main adverse effects of RRSO are related to premature surgical menopause, including short-term effects like vasomotor symptoms (i.e. hot flushes), sleep disturbances, vaginal dryness, and sexual symptoms. Long-term effects include osteoporosis, increased risk of cardiovascular disease, cognitive impairment, and increased depressive and anxiety symptoms. Based on recent scientific insights, nowadays the Fallopian tube is considered the most important site of origin of pelvic high-grade serous carcinoma. It is suggested that benign tubal epithelium can transform into serous tubal intraepithelial carcinoma (STIC) or invasive tubal carcinoma. The (pre)malignant cells can exfoliate from the tubal epithelial lining and migrate to the ovary and abdominal cavity. This theory is based on several findings. First, no clear precursor of ovarian cancer has been found in the ovary itself. Second, our group, amongst others, has demonstrated the presence of STIC lesions in the tubes of BRCA1 and BRCA2 mutation carriers. Earlier studies showed the presence of STIC in 36–60 % of sporadic pelvic serous carcinomas which harbored identical mutation in the TP53 gene to the cells of concurrent pelvic serous carcinomas in 92 %. Third, pelvic serous carcinoma cells resemble tubal lining epithelium more than ovarian surface epithelium. The growing evidence of the role of the Fallopian tube in the origin of serous ovarian carcinoma together with the disadvantages of premature surgical menopause caused by RRSO, underlie the need for an alternative risk-reducing strategy. Our group (de Hullu and Hermens) have developed the first national study in which RRSO is compared to RRS as a risk-reducing intervention (Health Expect 2018). The main advantage of delaying subsequent RRO beyond the currently recommended age will be postponement of premature menopause and its effect on non-cancer-related morbidity and (menopause-related) quality of life (QoL).