Oral Contraceptives and Breast Cancer (1991) / Chapter Skim
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Appendix A: Oral Contraceptives and Breast Cancer: A Review of the Epidemiological Evidence with an Emphasis on Younger Women
Appendix A: Oral Contraceptives and Breast Cancer: A Review of the Epidemiological Evidence with an Emphasis on Younger Women
Pages 73-101
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From page 75... ...
Breast cancer incidence in Western countries is relatively high and apparently is increasing. That breast cancer appears to be influenced by other hormonally mediated factors leads to the hypothesis that the high rate of exposure to oral contraceptives among American women may also be associated with this increase.
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From page 76... ...
There are four major types of oral contraceptives. Combination pills, which contain fixed amounts of estrogen and progestin and act by suppressing ovulation, were the first oral contraceptive approved in the United States (in the early 1960s)
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From page 77... ...
They have never had a significant share of the market. Phasic oral contraceptives, combination pills that contain estrogen along with a progestin dose that varies in amount throughout the month, were introduced in 1983 and have since become increasingly popular.
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From page 78... ...
Cancer risk is thought to be a function of the number of cells at risk, which varies with age. It is possible to posit that any carcinogenic risk of oral contraceptives may be strongly mediated by age of exposure or by the timing of exposure in relation to other events that are thought to affect epithelial proliferation or differentiation (e.g., menarche, first full-term pregnancy)
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From page 79... ...
Overall, there is no evidence of increased risk of breast cancer in women who meet the criterion of "ever" using oral contraceptives. The finding of no association between "ever" use of oral contraceptives and breast cancer risk has been quite consistent throughout the past 20 years of research.
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From page 80... ...
dWHO = World Health Organization; CASH = Cancer and Steroid Hormone Study.
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From page 81... ...
The largest case-control study of breast cancer conducted to date, the CASH study, showed no evidence of an association of breast cancer risk and long-term use of oral contraceptives among women aged 20 to 54 (CASH, 1986~. Yet despite its size (the study comprised more that 4,700 cases and a similar number of controls in eight geographic regions of the United States)
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From page 82... ...
82 APPENDIX A TABLE A-2 Summary of Risk Estimates for Lifetime Duration of Oral Contraceptive Use Duration Diagnosis of Use Relative Confidence Author/Year Age Dates (years) Riska Interval Vessey et al., 1983 16-50 1968-80 <1 0.9 0.7-1.1 >1-4 1.0 0.8-1.3 >4-8 1.2 0.8-1.6 >8 1.0 0.7-1.5 Hennekens et al., 1984 30-55 1960-76 <1 1.1 0.9-1.4 1-2 1.1 0.9-1.5 3-4 0.7 0.5-1.1 5-9 1.1 0.8-1.4 10+ 0.7 0.4-1.3 Rosenberg et al., 1984 20-59 1976-81 <1 0.9 0.7-1.1 1-4 0.9 0.8-1.2 5-9 1.3 1.0-1.7 10+ 0.8 0.5-1.3 CASH,b 1986 20-54 1980-82 6-9 1.Oc 10-14 1.1 15+ 0.6 Ellery et al., 1986 25-64 1980-82 2.1-6 0.7 0.3-1.5 6+ 1.0 0.5-2.0 La Vecchia et al., 1986 <60 1982-85 <2 1.0 0.7-1.4 >2 1.1 0.7-1.6 Lipnick et al., 1986 30-55 1976-80 <1 0.9 0.7-1.3 in 1976 1-2 0.8 0.6-1.1 3-4 1.0 0.7-1.4 5-9 1.2 0.8-1.5 10+ 1.3 0.9-1.9 Meirik et al., 1986 <45 1984-85 4-7 1.2 0.8-1.9 8-11 1.4 0.8-2.3 12+ 2.2 1.2-4.0 Paul et al., 1986 25-54 1983-85 6-9 0.8C 10+ 1.0 Lee et al., 1987 25-58 1982-84 5-9 1.2 0.6-2.3 10+ 1.0 0.4-2.6 McPherson et al., 1987 16-64 1980-84 Among women <45 4-12 1.2 0.8-1.8 13+ 1.8 0.8-3.9 Among women 45+ 4-12 1.1 0.7-1.6 13+ 0.8 0.4-1.8 Kay and Hannaford, 15-45 1988 (cohort)
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From page 83... ...
served a twofold excess risk for oral contraceptive use of five to nine years' duration and a fourfold excess risk for use of 10 or more years. Questions have been raised about Miller's findings because of concern about the appropriateness of the hospitalized control group and because there appears to be a lower proportion of exposed controls than would be expected from national data.
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From page 84... ...
This excess risk was confined to women between ages 40 and 50. Tumors in current users were reported to be larger and to have more lymph node involvement at the time of diagnosis than were tumors in women not currently using oral contraceptives.
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From page 85... ...
Table A-3 summarizes the findings regarding oral contraceptive use before FFTP. The vast majority of investigations of the relationship between oral contraceptive use prior to FFTP and breast cancer risk have focused on women under age 45.
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From page 86... ...
bConfidence intervals not provided by author. CResults are for nulliparous women aged 20-44 whose menarche occurred before age 13.
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From page 87... ...
A number of analyses found no suggestion of increased breast cancer risk for oral contraceptive use before FFTP (Paul et al., 1986; lick 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~.
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From page 88... ...
CWHO = World Health Organization. Duration Since First Use of Oral Contraceptives (Latency)
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From page 89... ...
Use of Oral Contraceptives in High-Risk Subgroups Although many investigators adjust for high-risk factors (e.g., family history of breast cancer, history of benign breast disease) in their analyses, only a subset have examined oral contraceptive use within each of these strata.
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From page 90... ...
In a follow-up study, similar questions arise concerning the possible differential distribution of disease occurrence. Table A-5 itemizes the following characteristics for most of the studies addressed here: diagnosis dates and the ages of women at the time of diagnosis, proportion of cases and controls who participated, sample size, proportion of cases and controls who reported "ever" using oral contraceptives, and whether controls were secured from hospitals.
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From page 91... ...
aControls were recruited from hospitals. bThe study dropped women who had ever used oral contraceptives but whose use was less than 8 years in duration.
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From page 92... ...
may not have had adequate power to evaluate the relationship of oral contraceptives and breast cancer. In addition, sample sizes need to be even larger to examine the interrelationships of other risk factors with oral contraceptive use (Greenland, 1983; Smith and Day, 1984~.
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From page 93... ...
Some of these risk factors, as well as some other factors, may also affect the decision to use oral contraceptives, the age of first and last use, and the lifetime duration of use. These and other factors may modify or be modified by the relationship of oral contraceptives to breast cancer risk.
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From page 94... ...
Thus, it is possible that oral contraceptive users are seen by the health care system more frequently than other women, and may receive more frequent medical surveillance, including breast exams and even mammograms. This hypothesis has led to the suggestion that women with breast cancer who use oral contraceptives are detected and diagnosed earlier than nonusers.
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From page 95... ...
5. Little is known about the relationship between various formulations of the pill and breast cancer risk, largely because no reliable classification system of the effects on the breast of oral contraceptives and their components has been developed.
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From page 96... ...
Studies conducted in the latter half of the 1980s may be the first conducted in women born recently enough to have used oral contraceptives at a young age and for a long enough duration and whose use preceded the diagnosis of disease by a sufficient amount of time to be consistent with a latent period for breast carcinogenesis. Oral contraceptives may have a differential effect on young breast tissue, and this effect may just have become detectable in the more recent studies.
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From page 97... ...
The recent FDA decision to lift the recommended upper age limit for use of oral contraceptives will probably lead to increased use in the over-40 age group. The relationship between oral contraceptives and breast cancer risk also needs to be examined in other subgroups, such as women with a strong family history of breast cancer and women with previous benign breast disease, using data sets with sufficient numbers of subjects.
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From page 98... ...
1978. Oral contraceptives and breast disease.
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From page 99... ...
1986. Oral contraceptives and breast cancer: A prospective cohort study.
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From page 100... ...
1981. Breast cancer and oral contraceptives: Findings in the Oxford-Family Planning Association contraceptive study.
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From page 101... ...
1989. Oral contraceptives and breast cancer: Latest findings in a large cohort study.
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