Combined Oral Contraceptives

Almost all studies of combined oral contraceptives and breast cancer have published results on the risk of breast cancer associated with ever use of such contraceptives. Overall it appears that women who have used combined oral contraceptives are at a very slightly increased risk of breast cancer [relative risk (RR) = 1.07, 95% confidence interval (CI) 1.03-1.10], although estimates from individual studies are by no means consistent (Fig. 6.1). This is perhaps not surprising since ever use is a very crude measure of exposure and is likely to represent quite different patterns of use in different studies.

When breast cancer risk is examined in relation to various aspects of oral contraceptive use, it is clear that recency of use is the aspect most closely associated with breast cancer risk. Figure 6.2 shows the pattern of breast cancer risk in users of combined oral contraceptives compared to never-users according to time since last use. It illustrates the fact that while women are taking combined oral contraceptives they experience a small increase in the risk of breast cancer (RR = 1.24, 95% CI 1.16-1.32) but that once they cease use this excess risk declines gradually so that by about 10 years after ceasing use they are no longer at any excess risk. Once recency of use is taken into account, no other aspect of combined oral contraceptive use appears to materially alter a woman's risk of breast cancer. In particular, the magnitude of the excess RR of breast cancer among current and recent users of combined oral contraceptives is not affected by a woman's total duration of use. The slight increase in breast cancer risk associated with current or recent use of combined oral contraceptives has been found consistently across

Figure 6.1 Relative risk (RR) of breast cancer in ever-users of combined oral contraceptives compared with never-users. Each relative risk estimate and its 99% confidence interval (CI) is plotted as a black square and a line. The area of each square is proportional to the amount of statistical information available for that particular estimate. Amer Canc Soc, American Cancer Society; Canadian NBSS, Canadian National Breast Screening Study; CASH, Cancer and Steroid Hormones; FPA, Family Planning Association; RCGP, Royal College of General Practitioners; SE, standard error; WISH, Women's Interview Study of Health; WHO, World Health Organisation. (Adapted from the Collaborative Group on Hormonal Factors in Breast Cancer.3)

Study

Relative risk of breast c in ever-users vs never-i RR and 99% CI

Prospective studies

RCGP Oxford/FPA Nurses Health Canadian NBSS Amer Canc Soc Netherlands Cohort Other

All prospective studies

Case-control studies with population controls

Brinlon 1.07 (0.075)

Berstein/Pike 1.01(0.218)

UK National 1.21(0.197)

Bain/Siskind 0.88(0.167)

Ewertz 0.95(0.109)

Meirik/Lund 1.23(0.171)

Long Island 1.27(0.150)

Clarke 0.92(0.139)

Yu/Yuan/Wang 1.16(0.163)

Paul/Skegg 1.07(0.124)

Daling 1.00(0.194)

Rookus/van Leeuven 1.06 (0.163)

Yang/Gallagher 0.76(0.118)

Primic-Zakelj 1.05(0.135)

Other 1.10(0.081) All case-control studies with „ ,„ population controls • I ■ I

Case-control studies with hospital controls

Ravnihar 1.57(0.164)

WHO (developing) 1.17(0.081)

Clavel 1.22(0.166)

LaVecchia 1.38(0.122)

Franceschi 1.27(0.111)

Other 1.10(0.104) All case-control studies with 1 17 /n „ .

All studies 1.07(0.017)

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