Oral Contraceptives and the Risk of Hereditary Ovarian Cancer

Narod, Steven A.; Risch, Harvey A.; Moslehi, Roxana; Dørum, Anne; Neuhausen, Susan L.; Olsson, Håkan; Provencher, Diane; Radice, Paolo; Evans, Gareth; Bishop, Sue Marquis; Brunet, Jean‐Sébastien; Ponder, Bruce A.J.; Klijn, Jan G.M.

doi:10.1056/nejm199808133390702

Cited by 562 publications

(194 citation statements)

References 10 publications

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“…1,13 Furthermore, an inverse relation between OC use and ovarian cancer risk was present in women with and without a family history of breast or ovarian cancer. 25,26 With regard to time-related factors, the present analysis shows that OCs convey protection for a long time after stopping use (at least 20 years). An apparent leveling off of this effect after 20 years since last use was no more evident after taking into account duration of use.…”

Section: Discussionmentioning

confidence: 69%

Long‐term effects of oral contraceptives on ovarian cancer risk

Bosetti

Negri

Trichopoulos³

et al. 2002

Intl Journal of Cancer

103

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Epidemiologic studies conducted since the late 1970s have reported a protective effect of oral contraceptives (OCs) from ovarian cancer and a stronger reduction of risk for longer duration of use. 1-3 An indication of a favorable impact of OC on ovarian carcinogenesis comes also from descriptive epidemiology. In several developed countries, young women have shown substantial decreases in incidence of and mortality from ovarian cancer, and the downward trends are greater in countries where OCs are widely used. 4 -7 However, there remain open issues on the relation between OC use and ovarian cancer, including a better quantification of timerelated factors, notably time since last use, age at first use and time since first use. Some of the studies that have considered time since last OC use have reported that the favorable effect of OCs on ovarian cancer risk persists for at least 15 years after stopping use. 2,8 -11 A few studies, however, have assessed the risk with longer time since last use. 12-16 A cohort analysis of ovarian cancer incidence and mortality rates in U.S. women over the period 1970 -1995 7 indicated that the relative decrease in incidence is greater before age 50. There is, therefore, a suggestion that the protection declines with time since last use, but the data are inconclusive. 2 In addition, few studies have simultaneously addressed all time factors, so the possibility of residual confounding in some of these studies cannot be excluded.To clarify the time relation between OC use and ovarian cancer risk, we conducted a collaborative reanalysis of European casecontrol studies of epithelial ovarian cancer. MATERIAL AND METHODSIn the present analysis, data from 6 case-control studies conducted in the United Kingdom, Greece and Italy were combined, i.e., all studies on OC and ovarian cancer published from Europe. The study design and methods have already been described. 12 Briefly, the first was a hospital-based investigation conducted in London and Oxford, UK, between 1978 and 1983. 17 Cases were 235 women under 65 years of age with epithelial ovarian cancer; controls were 451 women of comparable age, hospitalized for gastrointestinal diseases (23%), bone or joint diseases including fractures (22%) and a large number of other diagnostic categories, each including Ͻ10% of the total number of controls.The second study included 150 patients with malignant epithelial tumors of the ovary, admitted during 1980 and 1981 to 10 large hospitals of the Greater Athens area, Greece, 18 and 250 controls of similar age, hospitalized in the same time period in Athens hospitals for orthopedic conditions (among which 62% were traumas).The third study included 189 cases of epithelial ovarian cancer admitted to 2 major hospitals in Athens between 1989 and 1991. 19 Controls were 200 women, resident in the Greater Athens area, visitors of patients hospitalized in the same ward as cases in the same time period. Both cases and controls were below 75 years of age.The fourth study was a hospital-based investigatio...

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Section: Discussionmentioning

confidence: 69%

Long‐term effects of oral contraceptives on ovarian cancer risk

Bosetti

Negri

Trichopoulos³

et al. 2002

Intl Journal of Cancer

103

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“…To our knowledge, there are no other data available concerning other nonsurgical strategies to reduce gynecologic cancer risks in this population, such as oral contraceptives (OCPs) or progestin intrauterine devices. OCPs decrease endometrial and ovarian cancer risks in the general population by approximately 50%, [34][35][36][37][38][39][40][41][42][43] and progestin intrauterine devices may reverse hyperplasia and early endometrial cancer. 44,45 Because Lynch syndrome-associated gynecologic cancers appear to be similar to sporadic cases, 4,46 these chemoprevention strategies may be beneficial with less adverse effect on quality of life than prophylactic surgery.…”

Section: Discussionmentioning

confidence: 99%

Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

Kwon

Sun

Peterson

et al. 2008

Cancer

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BACKGROUND. Women with Lynch syndrome (hereditary nonpolyposis colorectal cancer) have an increased lifetime risk for endometrial and ovarian cancer. Screening and prophylactic surgery have been recommended as prevention strategies. In this study, the authors estimated the net health benefits and cost‐effectiveness of these strategies in a Markov decision‐analytic model. METHODS. Five strategies were compared for a hypothetical cohort of women with Lynch syndrome: 1) no prevention (‘reference’); 2) prophylactic surgery (hysterectomy and bilateral salpingo‐oophorectomy) at age 30 years; 3) prophylactic surgery at age 40 years; 4) annual screening with endometrial biopsy, transvaginal ultrasound, and CA 125 from age 30 years; and 5) annual screening from age 30 years until prophylactic surgery at age 40 years (combined strategy). Net health benefit was measured in quality‐adjusted life years (QALYs), and the primary outcome measured was the incremental cost‐effectiveness ratio (ICER). Baseline and transition probabilities were obtained from published literature, and costs were from the U.S. Department of Health and Human Services and Agency for Health Care Quality and Research. Sensitivity analyses were performed for uncertainty around various parameters. RESULTS. The combined strategy provided the highest net health benefit (18.98 QALYs) but had an ICER of $194,650 per QALY relative to the next best strategy (prophylactic surgery at age 40 years). Prophylactic surgery at age 30 years and annual screening were dominated by alternate strategies. CONCLUSIONS. Annual screening followed by prophylactic surgery at age 40 years was the most effective gynecologic cancer prevention strategy, but the incremental benefit over prophylactic surgery alone was attained at substantial cost. The ICER would become favorable by improving the effectiveness and reducing the costs of screening in this population. Cancer 2008. © 2008 American Cancer Society.

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“…It is important to establish whether or not oral contraceptives are hazardous to the breast, because their use has been proposed as a preventive measure against ovarian cancer (in a recent study of 232 ovarian cancer cases and 232 controls, oral contraceptive use was associated with a 56% reduction in the risk of ovarian cancer (OR ¼ 0.44; P ¼ 0.002) Narod et al, 1998). There appears to be a small increase in breast cancer risk associated with pill use among BRCA1 mutation carriers (Narod et al, 2002).…”

Section: Oral Contraceptivesmentioning

confidence: 99%

Modifiers of risk of hereditary breast cancer

Narod

2006

Oncogene

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Mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of breast and ovarian cancer. The risk varies from individual to individual, and it appears that the risk has increased in recent generations. These observations imply that non-genetic factors may modify the inherited risk. To date, the factors that appear most strongly to modify the risk include reproductive histories and exogenous hormones. Oral contraceptives are associated with a profound reduction in the risk of ovarian cancer, and with little or no increase in the risk of breast cancer. Other modifying factors include age of menarche, parity, breastfeeding and oophorectomy. The effect of parity is different in BRCA1 and BRCA2 carriers. Multiparity appears to be protective in BRCA1 carriers, but is associated with an increase in risk in BRCA2 carriers. Oophorectomy has been associated with reductions in both the risk of breast and ovarian cancer. Knowledge of these risk factors will be useful for managing risk and for developing prevention strategies.

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Oral Contraceptives and the Risk of Hereditary Ovarian Cancer

Abstract: Oral-contraceptive use may reduce the risk of ovarian cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene.

Cited by 562 publications

References 10 publications

Long‐term effects of oral contraceptives on ovarian cancer risk

Long‐term effects of oral contraceptives on ovarian cancer risk

Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

Modifiers of risk of hereditary breast cancer

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