use prior to FFTP, an RR of 1.7 (CI = 1.1-3.8) for four to seven years of use before FFTP, and an RR of 2.1 (CI = 0.8-4.7) for use of eight or more years before FFTP. Different interviewers were used for cases versus controls, however, and the response rates were rather low in this study, raising concerns about the findings.
A number of analyses found no suggestion of increased breast cancer risk for oral contraceptive use before FFTP (Paul et al., 1986; Jick et al., 1989; Romieu et al., 1989; WHO, 1990). Overall consideration of oral contraceptive use before FFTP in the complete Cancer and Steroid Hormone study data revealed no suggestion of excess breast cancer risk in the study's first report on the entire data set (Stadel et al., 1985). However, in a recent analysis of a “high-risk” subgroup of the CASH study subjects—nulliparous women with an early age of menarche diagnosed with breast cancer before age 45— an excess risk of breast cancer was seen in relation to increasing duration of oral contraceptive use (Stadel et al., 1988). The risk for oral contraceptive use of 8 to 11 years was 2.7, and the risk for use of 12 or more years was 11.8. A recent letter by Peto (1989) presented a crude reanalysis of the published CASH data that challenged an earlier conclusion of the study of no excess risk for use before FFTP.
Eight studies, which are summarized in Table A-4, have reported on use before age 25. Three studies (Stadel et al., 1985; Miller et al., 1986; McPherson et al., 1987) have shown no indication of a relationship with breast cancer risk, whereas four (Pike et al., 1983; Meirik et al., 1986; Olsson et al., 1989; WHO, 1990) suggest a positive relationship and one (Paul et al., 1986) suggests a protective effect. Pike and coworkers' 1983 study, in an expansion of the 1981 investigation, observed a significant dose-response pattern of increased risk for increased duration of use before age 25. For such use exceeding five years' duration, there was a 4.9-fold excess risk. In the data from Meirik and colleagues (1986), among Swedish and Norwegian women, there was no elevation in risk for use of less than eight years' duration prior to age 25, but there was an increased risk of 2.7 (CI = 0.7-11.0) for use of eight years or more before age 25. The Olsson team's 1989 study, also among Swedish women, reported a suggestive dose-response pattern for increasing duration of oral contraceptive use prior to age 25, with a 1.6-fold excess risk for use of less than three years before age 25, a twofold excess risk for use of three to five years, and a 5.3-fold excess risk for use exceeding five years.
A major challenge in interpreting many of the studies of use at a young age lies in separating the effects related to use early in life from effects associated with longer durations of exposure. More attention needs to be given to this issue in future analyses, particularly in populations in which the majority of the women were born recently.