Ovarian Cancers Evolving Paradigms in Research and Care (2016) / Chapter Skim
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3 Prevention and Early Detection
3 Prevention and Early Detection
Pages 97-146
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From page 97... ...
In particular, this chapter identifies a number of gaps in knowledge related to identifying those women who are at highest risk for developing ovarian carcinomas, and it describes several challenges to developing screening tests for high-risk women, their families, and the general population. The chapter also explains how gaps in knowledge about the basic biology of ovarian carcinomas (as discussed in Chapter 2)
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From page 98... ...
cycles SOURCE: Adapted from Permuth-Wey et al., 2014. cancer risk factors can also vary by histologic subtype, and thus a given risk factor may increase risk for one subtype while decreasing risk for another.
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From page 99... ...
. Germline mutations in these genes are present in approximately 10 to 15 percent of all women diagnosed with invasive ovarian carcinomas and in approximately 15 to 23 percent of women diagnosed with HGSC (Alsop et al., 2012; Pal et al., 2005; Risch et al., 2006; Zhang et al., 2011)
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From page 100... ...
. ASCO further stated that providers with expertise in cancer risk assessment need to be involved in ordering and interpreting multigene panels when genes of uncertain clinical utility are included and that patients must give informed consent and be provided with pretest counseling prior to any genetic testing.
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From page 101... ...
. Studies using consortia have identified as many as 17 low-penetrance SNP alleles associated with ovarian cancer risk (Bojesen et al., 2013; Bolton et al., 2010; Goode et al., 2010; Kuchenbaecker et al., 2015; Permuth-Wey et al., 2013; Pharoah et al., 2013; Song et al., 2009)
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From page 102... ...
Preventive Services Task Force (USPSTF) , all of the organizations recommend that all women diagnosed with ovarian carcinoma receive referral for genetic counseling and testing regardless of their family history.
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From page 103... ...
b Family history includes first- or second-degree relatives, and third-degree relatives in some recommendations. NOTE: ACMG = American College of Medical Genetics and Genomics; ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network; NSGC = National 103 Society of Genetic Counselors; SGO = Society of Gynecologic Oncology; USPSTF = U.S.
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From page 104... ...
For some of these factors, there is not yet a robust evidence base for their association with ovarian cancer risk, particularly by tumor subtype. Oral Contraception and Parity Among the most well-established risk factors for ovarian cancer are the use of oral contraceptives (OCs)
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From page 105... ...
FIGURE 3-1 Cascade genetic screening of BRCA mutation for HBOC syndrome. NOTE: HBOC = hereditary breast and ovarian cancer.
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From page 106... ...
While the results have been somewhat inconsistent, several larger studies with long follow-up have found little or no association of clomiphene citrate (an ovulatory stimulant) or exogenous gonadotropins with ovarian cancer risk, although one study did find suggestive evidence of an increased risk for nulliparous women using clomiphene citrate (Jensen et al., 2009; Trabert et al., 2013)
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From page 107... ...
. One small study of endogenous hormones that included estrogen and progesterone found that neither of these hormones had a significant association with ovarian cancer risk, although a more recent study found that high estradiol levels during pregnancy were associated with an increased risk of endometrioid tumors (Helzlsouer et al., 1995; Schock et al., 2014b)
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From page 108... ...
. Behavioral and Inflammatory Risk Factors In general, lifestyle factors such as diet, physical activity, adiposity, and smoking have not been strongly associated with ovarian cancer risk.
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From page 109... ...
. While height is consistently associated with an increased risk of ovarian cancer, associations of ovarian cancer risk with various measures of adiposity have been inconsistent, possibly because of differences due to menopausal status (Aune et al., 2015)
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From page 110... ...
. One analysis reported a 9 percent lower ovarian cancer risk with regular aspirin use, with stronger results among daily users (Trabert et al., 2014)
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From page 111... ...
In some studies, serologic evidence of chlamydia infection, a common cause of PID, has been associated with an increased ovarian cancer risk, particularly for cancer arising in the fallopian tube (Idahl et al., 2011; Ness et al., 2003, 2008)
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From page 112... ...
The inability to demonstrate clear associations for certain risk factors may be due in part to the limited power of individual studies to assess associations by tumor type. The complex associations that these factors have with ovarian cancer risk are driven in part by the differing etiologies for the diverse ovarian cancer subtypes.
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From page 113... ...
BSO, also known as risk-reducing salpingo-oophorectomy (RRSO) , is the surgical removal of the fallopian tubes and ovaries, which dramatically reduces the risk of ovarian cancer in women at average risk and high risk due to inherited genetic susceptibility (see Table 3-5)
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From page 114... ...
For example, BSOR may be most effective in preventing the ovarian carcinoma subtypes postulated to arise in the fallopian tubes. Furthermore, BSOR can prevent retrograde menstrua
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From page 115... ...
was associated with a 35 percent reduction in ovarian cancer risk (Falconer et al., 2015)
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From page 116... ...
But there are also some risks associated with OC use, including a slightly increased breast cancer risk and a two- to threefold higher risk of venous thromboembolism and ischemic stroke (Bassuk and Manson, 2015; Havrilesky et al., 2013)
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From page 117... ...
. The following sections discuss how these and other biomarkers have affected our understanding of ovarian cancer risk and describe these biomarkers' utility in screening and early detection.
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From page 118... ...
. The biology behind CA-125's apparent association with ovarian cancer risk and prognosis is currently unclear.
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From page 119... ...
. Subsequent research confirmed this expression pattern in ovarian carcinomas, and additional work in cell and animal models suggested a role for HE-4 in mediating resistance to chemotherapy and promoting tumor growth (Moore et al., 2014; Welsh et al., 2001)
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From page 120... ...
Overall, TVU has not yet shown value as a primary screening tool for ovarian cancer, but it may be useful with specific populations (e.g., women at high risk) or in conjunction with biomarkers for ovarian cancer screening (van Nagell et al., 2007)
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From page 121... ...
. Only a few studies have examined the usefulness of this technique for ovarian cancer screening, and early results indicate there is a high likelihood of missing borderline and low-grade tumors when using 18F-FDG-PET/CT (Castellucci et al., 2007; Risum et al., 2007; Yamamoto et al., 2008)
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From page 122... ...
Once researchers have a better understanding of the cell of origin for each of the ovarian carcinoma subtypes, they may then have more success with the use of imaging technologies to find these ovarian carcinomas at earlier stages. SCREENING FOR OVARIAN CANCER Screening -- checking for disease when there are no symptoms (NCI, 2015)
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From page 123... ...
. Ovarian Cancer Screening Trials Early detection screening trials evaluate the effectiveness of screening strategies in reducing the morbidity and mortality from a disease.
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From page 124... ...
NOTE: CA-125 = cancer antigen 125; IOC/FT = invasive cancer or fallopian tube; MMS = multimodal screening; OC/FT = ovarian cancer or fallopian tube cancer; PLCO = prostate, lung, colorectal, and ovarian cancer screening; RCT = randomized controlled trial; ROCA = risk of ovarian cancer algorithm; TVU = transvaginal ultrasound; UKCTOCS = United Kingdom Collaborative Trial of Ovarian Cancer Screening; USS = ultrasound scanning. SOURCE: Adapted from Menon et al., 2014.
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From page 125... ...
. United Kingdom Collaborative Trial of Ovarian Cancer Screening The UKCTOCS is the largest randomized controlled ovarian cancer screening trial to date, with 200,000 women enrolled and each assigned to one of three arms in order to compare two screening strategies (Sharma et al., 2012)
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From page 126... ...
• While several risk factors for ovarian cancer have been identified, their associations with specific histologic subtypes require further clarification. • Not all women who carry germline genetic mutations in cancer predisposition genes have an apparent family history.
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From page 127... ...
• New mutations identified in recent sequencing studies need fur ther risk quantification before they can be integrated into clinical practice. • The current understanding of risk factors has limited utility in ac curately predicting risk at the individual level; thus, there is a clear need for improved and validated risk prediction models that can be used to screen the general population of women.
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From page 128... ...
2009. Reproduc tive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: Results from the International BRCA1/2 Carrier Cohort Study.
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From page 129... ...
2014. Non-steroidal anti-inflammatory drugs and cancer risk in women: Results from the Women's Health Initiative.
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2015. Salpingectomy as a means to reduce ovarian cancer risk.
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2015. Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment.
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2006c. Alcohol intake and ovarian cancer risk: A pooled analysis of 10 cohort studies.
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From page 133... ...
1989. The clinical correlates of serum CA125 in 169 patients with epithelial ovarian carcinoma.
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2015. Mod erate-to-vigorous physical activity and leisure-time sitting in relation to ovarian cancer risk in a large prospective U.S.
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collaborative trial of ovarian cancer screening ( KCTOCS) : A randomised controlled trial.
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2005. Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies.
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2013. Reproductive characteristics in relation to ovarian cancer risk by histologic pathways.
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2012. Non-steroidal anti-inflammatory drug use and ovarian cancer risk: Findings from the NIH-AARP Diet and Health Study and systematic review.
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2006. Recreational physical activity and sedentary behavior in relation to ovarian cancer risk in a large cohort of U.S.
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2011. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers.
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2008. Flavonoids and ovarian cancer risk: A case-control study in Italy.
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2002. Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk.
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2010. Cancer genetics: Risks and mechanisms of cancer in women with inherited susceptibility to epithelial ovarian cancer.
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2007. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk.
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2004. Sedentary behaviours and epithelial ovarian cancer risk.
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From page 146... ...
Gynecologic Oncology 121(2)
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