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Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk-reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493-506. © 2017 American Cancer Society.

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer. Research over the past decade has strongly suggested that "ovarian" HGSC arises in the epithelium of the distal fallopian tube, with serous tubal intraepithelial carcinomas (STICs) being detected in 5-10% of BRCA1/2 mutation carriers undergoing risk-reducing surgery and up to 60% of unselected women with pelvic HGSC. The natural history, clinical significance, and prevalence of STICs in the general population (ie, women without cancer and not at an increased genetic risk) are incompletely understood, but anecdotal evidence suggests that these lesions have the ability to shed cells with metastatic potential into the peritoneal cavity very early on. Removal of the fallopian tube (salpingectomy) in both the average and high-risk populations could therefore prevent HGSC, by eliminating the site of initiation and interrupting spread of potentially cancerous cells to the ovarian/peritoneal surfaces. Salpingectomy may also reduce the incidence of the 2 next most common subtypes, endometrioid and clear cell carcinoma, by blocking the passageway linking the lower genital tract to the peritoneal cavity that enables ascension of endometrium and factors that induce local inflammation. The implementation of salpingectomy therefore promises to significantly impact ovarian cancer incidence and outcomes.

Twenty percent of women with endometrial cancer will die from it, predominantly from systemic spread. Chemotherapy is, therefore, needed both for “high risk” women at diagnosis (stages III and IV–all histologies; stage II Clear Cell or grade 3; Papillary Serous or MMMT, irrespective of stage) and for relapsers, unless grade 1, when hormones are a preferable initial option. The most active single agents are: the anthracyclines, taxanes and platins; response rates 17–37, 21–67 and 13–14%, respectively. Combinations have proven to be superior in terms of relapse but not survival. Taxane-/platin-containing regimens are the phase III proven best combinations.

A variable flow fan aircraft propulsion system offers the potential for achieving a low specific thrust with high flow and low jet velocity requirement as specified for takeoff, side-line noise, initial climb, and a high specific thrust requirement for climb and acceleration to supersonic cruise. These requirements are conflicting. To achieve this, the operating envelope of a variable flow fan has to be expanded over existing turbofan engines. The variable flow fan concept (i.e., the Variable Fan Exit or “VFX”) can efficiently operate beyond the usual fan (or compressor) stall operating line using novel methods of designing and scheduling the fan geometry as a function of flight Mach Number, fan pressure ratio and corrected speed. Fan geometry is altered by using variable inlet guide vanes (IGV’s), variable stators, and variable outlet guide vanes (OGV’s).

Maximal surgical debulking plus platin-based chemotherapy is the standard of care. Most oncologists would use carboplatin plus paclitaxel. However, other equally valid options would include carboplatin plus docetaxel, single-agent carboplatin, or a combined intraperitoneal/ intravenous platin–paclitaxel regimen (for the subset with stage III disease and less than 1cm disease left after primary debulking). Failed strategies include adding a third cytotoxic, autologous bone marrow transplant, immune modulation using anti-CA 125 antibody or interferon, intraperitoneal radiolabeled antibody, modulating multidrug resistance with a cyclosporine analogue, and, finally, matrix metalloproteinase inhibition. The jury is still out with regard to maintenance paclitaxel. Dose-dense therapy, as with breast cancer, appears to have promise.