Description of the Evidence
Incidence and Mortality
In 2019, it is estimated that 22,530 new cases of ovarian cancer will be diagnosed and 13,980 deaths due to ovarian cancer will occur.[1] Incidence and mortality rates are higher among whites than among blacks, but statistically significant decreases in incidence and mortality rates have been observed among both whites and blacks.[2] In 2014, the overall incidence rate for ovarian carcinoma among women aged 65 years and older was 41.9 cases per 100,000 women-years.[3] Given that the Surveillance, Epidemiology, and End Results Program does not adjust for oophorectomy or salpingectomy, racial differences in the prevalence of women who had undergone these procedures could bias racial rate comparisons. A statistically significant decrease in delayed adjusted incidence of 0.9% among whites from 1987 to 2012 and 0.2% among blacks from 1992 to 2012 was observed. A statistically significant decrease in mortality rates of 2.0% per year among whites from 2002 to 2012 and 1.3% per year among blacks from 1992 to 2012 was observed. The population lifetime risk of ovarian cancer is 1.3%; the population lifetime risk of dying from ovarian cancer is 0.97%.[2]
Histology and Pathogenesis of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Ovarian carcinoma is a biologically and clinically heterogeneous class of tumors that includes several major subtypes: serous, mucinous, endometrioid, and clear cell. Classification of ovarian carcinomas into type I and type II tumors has been proposed. In this system, type I tumors include the following:[4]
- Endometriosis-related subtypes, such as endometrioid, clear cell, and seromucinous.
- Low-grade serous.
- Mucinous and malignant Brenner tumors.
Among type I tumors, endometrioid and clear cell carcinomas are numerically predominant and most important clinically. In general, type I ovarian carcinomas present at a lower stage than type II tumors and portend a better prognosis.
Type II tumors are comprised mainly of high-grade serous carcinomas, the most common and lethal of all ovarian carcinoma subtypes. These cancers usually present with symptomatic bulky stage III or IV disease and ascites. Many, but possibly not all, high-grade serous carcinomas appear to arise from malignant in situ lesions in the epithelium of the fallopian tube fimbria, which spread to the ovaries secondarily, but continue to be referred to as ovarian carcinomas. Evidence for a tubal origin is based mainly on examination of risk-reducing salpingo-oophorectomy specimens, performed among BRCA1/BRCA2 mutation carriers, in which incidental low-volume disease enables recognition of serous tubal intraepithelial carcinoma (STIC). However, not all women with high-grade serous carcinomas have identifiable STIC and few studies of the fallopian tubes among women who are not carriers of BRCA1/BRCA2 mutations have been performed, suggesting that pathogenesis of these tumors is not fully known. Serous carcinomas can be further divided on the basis of molecular characteristics.[5]
The heterogeneity in the etiology and pathogenesis of different ovarian cancer subtypes and variability in the classification of tumors over time and between studies pose challenges for interpretation of etiologic data. Ovarian cancer is a rare cancer, thus sample size and power of studies to detect moderate associations by cancer subtype is limited. However, clearer subtyping of cancers may assist in improving our understanding of the etiology of ovarian malignancies in future studies.
Factors With Adequate Evidence of an Increased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Family history and inherited susceptibility to ovarian, fallopian tube, and primary peritoneal cancer
Some women are at an increased risk because of an inherited mutation, with the magnitude of that risk dependent on the affected gene and specific mutation. Underlying ovarian cancer risk can be assessed through accurate pedigrees and/or genetic markers of risk. Because of uncertainties about cancer risks associated with certain specific gene mutations, genetic information may be difficult to interpret outside of families with a high incidence of ovarian cancer.
This summary does not address multiple genetic syndromes or women who are at high risk because of inherited genetic factors. (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers and Genetics of Colorectal Cancer for specific information related to ovarian cancer risk associated with multiple genetic syndromes and ovarian cancer in BRCA1/BRCA2 mutation carriers.)
Hormone replacement therapy/hormone therapy
A meta-analysis of 52 studies (17 prospective and 35 retrospective) including 21,488 ovarian cancers found increased risks with current or recent hormone replacement use in prospective studies (relative risk [RR], 1.37; 95% confidence interval [CI], 1.29–1.46), with similar results for retrospective designs. Significant relationships were found for serous and endometrioid subtypes.[6] Recent use was strongly related to risk even among women who had used hormone replacement for less than 5 years (RR, 1.41; 95% CI, 1.32–1.50). Risk declined among women who had discontinued use, with greater effects for longer periods of cessation. Risks did not differ by preparation types (estrogen only vs. combined estrogen/progestin). Risks also did not differ by age at use.[7,8]
Obesity and height
Ovarian cancer risk increases with increasing height and weight (body mass index [BMI]).[9] The Collaborative Group on Epidemiological Studies of Ovarian Cancer compiled individual data, both published and unpublished, from 47 epidemiological studies including 12,157 women with ovarian cancer and 81,311 controls. RR increased significantly with increasing height (1.07 per 5 cm height) and with increasing BMI (1.10 per 5 kg/m2). These findings were unaffected by other factors known to be associated with ovarian cancer risk, with the exception that ever-users of hormone therapy had no increased risk with increasing BMI. Given that height, weight, and BMI are thought to be strongly correlated, separating out the individual effects can be difficult. Ovarian cancer mortality has also been shown to be increased in obese women.[10,11]
Factors With Adequate Evidence of a Decreased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Oral contraceptives
A collaborative analysis was performed of individual data from 23,257 women with ovarian cancer and 87,303 women without ovarian cancer from 45 studies in 21 countries.[12] The studies included 13 prospective studies, 19 population-based case-control studies, and 12 hospital-based case-control studies. Oral contraceptive use was associated with a dose-response effect by duration of use, without observed changes in risk reduction by decade of use from the 1960s to 1980s, over which time the amount of estrogen in oral contraceptives was approximately halved. No risk reduction was observed for women who used oral contraceptives for less than 1 year. The risk reduction associated with use from 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 years or more was 0.78 (99% CI, 0.73–0.893), 0.64 (99% CI, 0.59–0.69), 0.56 (99% CI, 0.50–0.62), and 0.42 (99% CI, 0.36–0.49), respectively. The observed risk reduction persisted after cessation of oral contraceptive therapy but attenuated over time since last use. The proportional reduction in risk per 5 years of use was 29% (95% CI, 23%–34%) for women who had discontinued use within the last 10 years; the reduction in risk was 15% (95% CI, 9%–21%) for women who discontinued use 20 to 29 years ago.
A meta-analysis, in which the primary analysis was restricted to 24 case-control and cohort studies published since 2000 to reflect more recent types of oral contraceptive preparations, also observed a dose-response by duration of use.[13] The risk reduction among women using oral contraceptives for more than 1 year but less than 5 years was 0.77 (95% CI, 0.66–0.89), and for women using oral contraceptives for more than 10 years, the risk reduction was 0.43 (95% CI, 0.37–0.51). The authors estimated that 185 women needed to be treated for 5 years to prevent one case of ovarian cancer. Based on an estimated lifetime risk of 1.38% and prevalence of ever-use of oral contraceptives of 83%, the authors estimated a lifetime reduction of ovarian cancer attributable to oral contraceptives of 0.54%.
(Refer to the PDQ summary on Genetics of Breast and Gynecologic Cancers for specific information related to ovarian cancer risk among BRCA1/BRCA2 mutation carriers.)
Depot-medroxyprogesterone acetate
Limited information is available on the use of injectable progestational contraceptives (depot-medroxyprogesterone acetate [DMPA]) and the risk of ovarian cancer; studies are confounded by the use of other contraceptive methods, particularly oral contraceptives. A hospital-based study conducted in Mexico and Thailand, with 224 cases and 1,781 controls (the World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives), did not observe an association between DMPA and ovarian cancer (RR, 1.07; 95% CI, 0.6–1.8).[14] However, only 22 of the cases had ever used DMPA and nine of these had used it for 6 months or less.
A subsequent multicenter study conducted in 12 hospitals in Thailand, including 330 cases and 982 matched controls, observed a statistically significant decreased risk of ovarian cancer associated with DMPA use, controlling for oral contraceptive use and other associated factors (odds ratio [OR], 0.52; 95% CI, 0.33–0.88). A dose-response association was observed but the sample size was limited in longer-term use categories.[15]
Tubal ligation
A meta-analysis of 16 case-control studies, three retrospective studies, and two prospective cohort studies observed a decreased risk of ovarian cancer associated with tubal ligation (RR, 0.66; 95% CI, 0.60–0.73).[16] The reduced risk was observed up to 14 years after tubal ligation. A population-based case-control study of 902 cases and 1,802 controls published subsequent to the meta-analysis observed an adjusted OR of 0.62 (95% CI, 0.51–0.75) associated with a history of a tubal ligation.[17] The association was adjusted for oral contraceptive use, which was also associated with a lower risk of ovarian cancer (OR, 0.62; 95% CI, 0.47–0.85) and other risk factors.[17]
Another pooling project with primary data from 13 population-based case-control studies examined the association between tubal ligation and ovarian cancer risk and included 7,942 epithelial ovarian cancers, and 13,904 controls.[18] Overall, tubal ligation was associated with a 29% reduction in risk (OR, 0.71; 95% CI, 0.66–0.77). The observed risk reduction varied by subtype of invasive cancers and was 52% (OR, 0.48; 95% CI, 0.40–49) for endometrioid cancer; 48% (OR, 0.52; 95% CI, 0.40–0.67) for clear cell cancer; 32% (OR, 0.68; 95% CI, 0.52–89) for mucinous cancer; and 19% (OR, 0.81; 95% CI, 0.74–0,89) for serous cancer.
A pooled analysis from 21 prospective cohort studies examined 14 hormonal, reproductive, and lifestyle factors by histologic subtype among 5,584 invasive ovarian cancers within a total sample of 1.3 million women. Overall, tubal ligation was associated with an 18% reduction in risk (OR, 0.82; 95% CI, 0.73–0.93). The observed risk reduction varied by subtype of invasive cancer and was 40% (OR, 0.60; 95% CI, 0.41–88) for endometrioid cancer; 65% (OR, 0.35; 95% CI, 0.18–0.69) for clear cell cancer; and 9% (OR, 0.91; 95% CI, 0.79–1.06) for serous cancer. There was a nonsignificant increase in risk of 1% (OR, 1.01; 95% CI, 0.60–1.71) for mucinous cancer.[19]
Breastfeeding
A meta-analysis [20] that included five prospective studies and 30 case-control studies examined the association between breastfeeding and the risk of ovarian cancer. Any breastfeeding was associated with a decreased risk of ovarian cancer (RR, 0.76; 95% CI, 0.69–0.83). The risk of ovarian cancer decreased 8% for every 5-month increase in duration of breastfeeding (95% CI, 0.90–0.95). Another meta-analysis that included five prospective studies and 35 case-control studies found that any breastfeeding was associated with a decreased risk of ovarian cancer (RR, 0.70; 95% CI, 0.64–0.76). These results are consistent with a previous meta-analysis and further support the prior finding of a suggested association between increased duration of breastfeeding and greater levels of protection.[21] Another meta-analysis of 19 studies, including four cohort and 15 case-control studies found an overall decreased risk of ovarian cancer with an OR of 0.66 (95% CI, 0.57–0.76) and an association with duration (2% decrease per month). The benefit of breastfeeding was greatest for the first 8 to 10 months.[22]
Risk-reducing salpingo-oophorectomy
Risk-reducing surgery is an option considered by women who are at high risk of ovarian cancer, such as those with an inherited susceptibility to cancer. (Refer to the Oral contraceptives section in the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information on this as a risk-reducing intervention.) Among women in the general population, opportunistic salpingectomy, oophorectomy, or salpingo-oophorectomy have been considered as possible interventions at the time of surgery for other benign indications. Salpingectomy has also been discussed as a preferred means of sterilization.[23,24]
Harms
Risks associated with benign oophorectomy (with or without salpingectomy or hysterectomy) have been analyzed in six published studies. Studies of three cohorts found that oophorectomy performed before menopause (age 45 or 50 years) was associated with increased overall mortality, likely related to cardiovascular disease. This finding was noted particularly among individuals not using hormone replacement. In the Women’s Health Initiative, bilateral salpingo-oophorectomy was not associated with increased mortality. In the National Health and Nutrition Examination Survey (NHANES III), oophorectomy overall was not related to mortality, but mortality was increased among obese women younger than 40 years who did not use hormone replacement. The California Teachers Study did not find a mortality risk with oophorectomy, but only 3% of women did not use hormone replacement. Overall, data suggest that oophorectomy among younger women likely increases overall mortality and that this risk may be attenuated with hormone replacement.[25-30]
Salpingectomy
Data relating salpingectomy to risk of ovarian/tubal cancer are limited, but consistent. A meta-analysis of three studies found an OR of 0.51 (95% CI, 0.35–0.71) for risk of these cancers among women who had undergone salpingectomy, compared with women who had intact fallopian tubes.[31] These studies included a Swedish record linkage study conducted from 1973 to 2009 with a mean follow-up of 23 years, which found the following hazard ratios (HRs) for risk of ovarian cancer compared with women who had not undergone surgery:
- For hysterectomy, the HR was 0.79 (95% CI, 0.70–0.88).
- For hysterectomy with bilateral salpingo-oophorectomy, the HR was 0.06 (95% CI, 0.03–0.12).
- For salpingectomy, the HR was 0.65 (95% CI, 0.52–0.81).
- For sterilization procedures, the HR was 0.72 (95% CI, 0.64–0.81).
Protection for bilateral salpingectomy was approximately twice that for unilateral salpingectomy.[32] This report included limited covariate data but results were similar to other smaller studies included in the meta-analysis.
.png)
No hay comentarios:
Publicar un comentario