Chemoprevention for Women with Increased Risk

In a similar fashion to studies in the general population, case-control investigations are used to determine the effect of oral contraceptive pills on women with an increased risk of ovarian cancer. Case-control studies face the same limitations with this group of subjects as those encountered in the general population. In addition, these investigations may be hampered by methods used to identify the subjects at risk for ovarian cancer. Some studies use family history, whereas others use formal genetic testing.

A case-control study performed by Narod and associates15 compared oral contraceptive use in 207 women with pathogenic mutations in BRCA1 (n = 179) or BRCA2 (n = 28) with 161 of their sisters. Any past use of oral contraceptive pills was associated with and adjusted odds ratio for ovarian cancer of 0.5 (95% CI, 0.3-0.8). The protective effect remained significant for carriers of the BRCA1 mutation but not the BRCA2 mutation. Given the small number in the BRCA2 mutation group, the investigation was probably not sufficiently powered to detect this difference.

Modan and colleagues16 conducted a population-based case-control investigation that first evaluated an Israeli population of 840 women with ovarian cancer and 751 controls for the presence of BRCA founder gene mutations. Mutations were identified in 29% (244 of 840) of patients with ovarian cancer and only 1.7% (13 of 751) of controls. Parity and oral contraceptive use reduced the risk of ovarian cancer in noncarriers. In BRCA mutation carriers, parity continued to provide a protective effect with each birth resulting in a risk reduction of 12% (95% CI, 2.3-21%. In contrast, oral contraceptive use in BRCA mutation carriers was associated with a nonsignificant reduction of 0.2% per year (95% CI, 4.9-5.0%). In another case-control investigation, Whittemore and associates17 identified 451 BRCA1 or BRCA2 mutation carriers of whom 147 women had ovarian cancer and 304 subjects did not. Using self-reported histories, they compared oral contraceptive pill use in the subjects. Ovarian cancer risk decreased by 5% (95% CI, 1.0-9.0) with each year of oral contraceptive pill use.

Although most investigations do not have access to BRCA mutation status, several have used a family history of ovarian cancer as a surrogate. Walker and associates18

Table 4-3. Ovarian Cancer Risk Reduction: Oral Contraceptives

in Women with an Increased Risk

Investigation

Population Odds Ratio

95% CI

Narod et al15 BRCA mutation 0.5 0.3-0.8

Modan et al16 BRCA mutation 1.07 (>5 years) 0.63-1.83

Whittemore et al17 BRCA mutation 0.62 (>6 years) 0.35-1.09

Walker et al18 Family history 0.07 (>4 years) 0.01-0.44

Bosetti et al14 Family history 0.50 0.26-0.95

Narod et al15 BRCA mutation 0.5 0.3-0.8

Modan et al16 BRCA mutation 1.07 (>5 years) 0.63-1.83

Whittemore et al17 BRCA mutation 0.62 (>6 years) 0.35-1.09

Walker et al18 Family history 0.07 (>4 years) 0.01-0.44

Bosetti et al14 Family history 0.50 0.26-0.95

interviewed 767 patients with epithelial ovarian cancer and 1367 control subjects to obtain personal and family data. Among those with a first-degree relative with ovarian cancer (33 case patients and 24 controls), risk of ovarian malignancy decreased with increasing duration of oral contraceptive use (P = .01). In fact with oral contraceptive use longer than 48 months, the protective effect was greater in subjects with a family history of ovarian cancer than in those without such a history. Bosetti and colleagues14 reanalyzed data from six European case-control studies. They identified 2768 women with epithelial ovarian cancer and 6274 control subjects. A significant reduction in risk of ovarian cancer was noted in ever users of birth control pills compared with never users (odds ratio 0.66; 95% CI, 0.56-0.79). The protective benefit remained for women with a family history of ovarian cancer.

Although the benefit was less extensive than in the general population, the majority of investigations support the use of oral contraceptives for the prevention of ovarian cancer in women with an increased risk of this malignancy. No studies have reported a deleterious effect in this population. Given the data, the recommendation of oral contraceptive pills for the prevention of ovarian cancer in high-risk patients is appropriate (Table 4-3).

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