11/8/2022 0 Comments Bso death proof downloadThe noncancer implications of BSO in postmenopausal women are less clear. Although effective, the overall public health impact of prophylactic BSO in high-risk women is relatively minor as only 7% to 10% of ovarian cancer occurs in mutation carriers. Prophylactic BSO is recommended at ages 35 to 40 years and once child bearing is complete for all women with hereditary breast and/or ovarian cancer syndrome. BSO has also been associated with a reduction in breast cancer risk, especially when performed in premenopausal women with BRCA2 mutations ( 40, 41). The residual risk of ovarian cancer is attributed to the failure to identify occult cancers at the time of the surgery, or the subsequent development of primary peritoneal cancer. A recent report from an observational cohort of roughly 5,800 mutation carriers confirms a similar reduction in ovarian cancer risk and importantly a 77% reduction in all-cause mortality to age 70 years ( 11). A meta-analysis that included 10 studies demonstrates that prophylactic removal of the fallopian tube and ovaries reduces future risk of ovarian cancer in high-risk women by >80% ( 25). The benefits of prophylactic BSO for women at increased genetic risk are clear. Evidence for Prophylactic Salpingo-Oophorectomy In these mice, HGSC metastasizes to the ovary and peritoneum much like the pattern seen in humans ( 38). The mutations resulted in HGSC and STIC arising from the fallopian tube as observed in the human disease. In this model, fallopian tube secretory cells were targeted for mutation of TP53, PTEN, and BRCA1 or BRCA2 using cell type–specific PAX8-driven Cre expression. Another new mouse model was recently reported that shows de novo HGSC arising from the fallopian tube. The transformed human FTSEC generated tumors in mice that resembled HGSC, an important proof-of-concept study confirming the potential for transformed fallopian tube cells to initiate tumorigenesis. Levanon and colleagues ( 37) reported a mouse model using human fallopian tube secretory epithelial cells (FTSEC) transformed using multiple oncogenes and transplanted by intraperitoneal injection into mice. New models have now been developed to focus on fallopian tube epithelium and better reflect the human disease, again adding credence to the fallopian tube site of origin. Preclinical ovarian cancer studies have historically relied on cultured ovarian surface epithelium, transgenic mouse models targeting the ovarian surface epithelium, or xenograft mouse models, all of which generally did not reflect the behavior of ovarian cancer in humans. STICs are characterized by increased nuclear size, hyperchromasia, nucleolar prominence, mitotic activity, and loss of cell polarity ( 28, 34). In addition to these findings in women with a genetic predisposition to ovarian cancer, subsequent studies found similar STICs and early invasive tubal carcinomas in 50% to 60% of women with sporadic ovarian cancer ( 28, 30, 32, 33). Lending support to the proposal that STICs are the precursor lesion to HGSC is the finding of identical TP53 mutations in STICs and both concomitant ovarian and/or peritoneal cancers ( 30, 31). These STIC precursor lesions closely resemble traditional HGSCs, and are not found in the corresponding ovaries of the prophylactic specimens. This view has recently been challenged by the identification of serous tubal intraepithelial carcinomas (STIC) and occult invasive serous carcinomas in 10% to 15% of the fallopian tubes examined from women with BRCA1/2 mutations who undergo BSO for prophylaxis ( 28, 29). Historically, it was assumed that ovarian tumorigenesis initiated in the ovarian surface epithelium (OSE) or from cortical inclusion cysts that contain OSE. There has been a remarkable paradigm shift in the understanding of the origin of HGSC. In this review, we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high-grade serous cancers (HGSC). Although this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it affects quality of life, and the premature cessation of ovarian function may have long-term health hazards. Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk reduction in women at hereditary risk of ovarian cancer.
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