Oral contraceptives and breast cancer

A population-based case-control study of oral contraceptive use and breast cancer was carried out among young women (less than 43 years of age) at Group Health Cooperative of Puget Sound, Seattle, Washington. Use of oral contraceptives before first pregnancy did not materially differ between cases or controls. The rate ratio estimate of breast cancer incidence in women who had used oral contraceptives before first pregnancy compared to those who had not was 0.9 (95% CI = 0.4, 2.1). There were no meaningful patterns of association between breast cancer and duration of use or formulation of oral contraceptive used before first pregnancy.     

Oral contraceptives and breast cancer: final report of an epidemiological study

During 1968-1980, 1176 women aged 16-50 years with newly diagnosed breast cancer and a like number of matched controls were interviewed at 9 teaching hospitals in London and Oxford and asked about their use of oral contraceptives. The results were reassuring. A few statistically significant differences in oral contraceptive use were found between the breast cancer and control groups, but the data were subdivided in many ways so that some "significant" differences would have been expected through the play of chance alone. Certainly no patterns of risk emerged which would suggest that any of the associations were causal. It must be stressed, however, that the data are still sparse in some important subcategories--for example, only small numbers of both cases and controls had prolonged oral contraceptive use before their first term pregnancy. For this reason, it is important that information on the possible relationship between pill use and breast cancer should continue to be collected. Women who had never used oral contraceptives presented with appreciably more advanced tumours than those who had been using oral contraceptives during the year before detection of cancer, while past users were in an intermediate position. These differences in staging were reflected in the pattern of survival. Possible explanations for these observations include "surveillance bias" among oral contraceptive users leading to earlier diagnosis and a beneficial biological effect of oral contraceptives on tumour growth and spread. Women with breast cancer reported never having used any method of contraception and heavy cigarette smoking (greater than or equal to 15 per day) significantly less often than controls. We could find no obvious explanation for the former observation, but suspect that the latter reflects the unrepresentative smoking habits of our hospital controls rather than a protective effect of smoking against breast cancer.     

Oral contraceptives and breast cancer: results from an expanded case-control study

The relationship between oral contraceptives and breast cancer was evaluated among 2,022 cases and 2,183 controls participating in a multicentre breast cancer screening programme. Ever use of oral contraceptives was not related to breast cancer risk (RR = 1.0, 95% CI 0.9-1.2), and no overall patterns of increasing or decreasing risks were observed according to the duration of use, or time since first or most recent use. Although we had no women with extended periods of oral contraceptive use early in life, no evidence of adverse effects attributable to short-term use before age 25, before first live birth or during the perimenopausal period were observed. Further, oral contraceptives did not interact with other breast cancer risk factors, except among those with a history of two or more breast biopsies (RR = 2.0). Analyses by stage of disease revealed that risk was related to the duration of oral contraceptive use: greater than or equal to 5 years use was associated with reduced risk for in situ cancer (RR = 0.59) and increased risks for invasive cancers (RR = 1.5 and 1.4 respectively for small and large lesions). These data suggest that oral contraceptive effects may vary by stage of disease, but provide no overall evidence of an association between oral contraceptives and breast cancer.     

Oral contraceptives and risk of breast cancer

A national population-based case-control study was conducted in New Zealand to assess the effects of hormonal contraception on breast-cancer risk. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk of breast cancer for women who had ever used oral contraceptives was 1.0 (95% confidence interval 0.82-1.3). There was no increase in risk with duration of use, even among women who had continued to use oral contraceptives for 14 or more years (relative risk = 1.1, 95% confidence interval 0.78-1.7). The risk of breast cancer was not increased by use of oral contraceptives for long periods before the first pregnancy or by starting use at a young age. Parity, age at menarche, family history of breast cancer, or history of benign breast disease did not modify the effect of oral contraceptives on breast-cancer risk. Relative risk estimates were slightly, although not significantly, increased during the first few years after starting oral contraception and in women under 35 years of age at diagnosis.     

Hormone replacement treatment and breast cancer risk: a cooperative Italian study.

The relationship between hormone replacement treatment (HRT) and breast cancer risk was analysed using data from a case-control study conducted between June 1991 and February 1994 in six Italian centres on 2569 patients aged below 75 with histologically confirmed breast cancer and 2588 controls admitted to hospital for a wide spectrum of acute, non-neoplastic, non hormone-related diseases. Ever HRT use was reported by 7.5% of cases and 7.5% of controls, corresponding to a multivariate odds ratio (OR) of 1.2 [95% confidence interval (CI), 0.9-1.5]. The risk increased with increasing duration of use: the ORs were 1.0 for use lasting less than 1 year, 1.3 for 1-4 years and 1.5 for 5 years or more. There was no clear pattern of risk with reference to time since starting use, but the OR was significantly elevated (OR = 2.0, 95% CI 1.3-2.9) for women who had stopped HRT within the last 10 years. No association was observed in those who had stopped HRT more than 10 years ago (OR = 1.0). The increased OR for women who had stopped HRT within the last 10 years was consistent across strata of identified covariates, and was significantly related to duration of use. This study confirms the absence of a strong association between HRT and breast cancer risk, although the risk estimate was above unity for women who had used HRT for 5 years or longer. However, the risk was significantly elevated in the short to medium term after use, particularly for long-term use. This short-term increased risk is consistent with an effect of HRT on one of the later stages of the process of breast carcinogenesis. The flattening of risk with increasing time since stopping, and hence the absence of a long-term cumulative excess in breast cancer risk after stopping HRT exposure, has relevant implications on individual risk assessment and public health.     

Oral contraceptives and breast cancer: latest findings in a large cohort study

During the interval 1968-74, 17,032 women aged 25-39 years were recruited to the Oxford-Family Planning Association contraceptive study, more than half of whom were using oral contraceptives. These women have been followed up over the years and breast cancer has been diagnosed in 189 of them. We have analysed the available data in two ways. First, we have calculated standardised breast cancer incidence rates in non-users and users of oral contraceptives according to total duration of use, interval since first use, interval since last use, duration of use before first term pregnancy and duration of use before age 25. Secondly, we have conducted case-control within cohort analyses to examine the possible effects of different types of pill and to search for evidence of a latent effect of oral contraceptive use before first term pregnancy on breast cancer risk. We have found no evidence of any adverse effect of oral contraceptive use on the risk of breast cancer in this study. There was, however, little exposure to the pill before first term pregnancy among the participants and virtually no such exposure at a very young age (i.e. below 20 years). Accordingly, the results of this study strengthen the evidence that oral contraceptive use by mature women does not increase breast cancer risk, but add little to the uncertainty about the effects of early use.     

Oral contraceptives and risk of familial breast cancer

The risk of breast cancer of oral contraceptive (OC) use in 1423 women from families with hereditary/familial breast cancer recruited through a cancer family clinic was analyzed in a matched case-control study. Ninety-eight women tested positive for a BRCA1 mutation. Hazard ratio for ever use of OCs adjusted for other risk factors was 0.90 (95% confidence interval (CI) 0.68-1.18) in the total data set and 2.00 (0.36-10.9) in BRCA1 mutation carriers. We did not find evidence for interaction between BRCA1 mutation status and OC use on breast cancer risk. Recent users had a statistically significant increase in risk with hazard ratios of 1.99, 2.05, and 1.69 for up to 5, 10, and 15 years since last OC use, while users with more than 15 years since last use had a reduction of risk to 0.69 compared to never users. We conclude that the effects of OC use on breast cancer risk in familial breast cancer may be similar to the effects in the general population. For BRCA1 mutation carriers, the point estimate is a doubling of risk, but CI is wide and no conclusion may be drawn from this study alone.     

Oral contraceptives and breast cancer. Review and meta-analysis

To evaluate the relation between use of oral contraceptives and the incidence of breast cancer, the authors reviewed the epidemiologic literature and used quantitative methods to summarize the data. Study results for any use of oral contraceptives were pooled using a model that accounted for both interstudy and intrastudy variability. The authors also explored interstudy variability and modeled a duration-effect relation between oral contraceptive use and breast cancer. Case-control and follow-up studies were considered separately. Overall, the authors observed no increase in the risk of breast cancer for women who had ever used oral contraceptives, even after a long duration of use. These results were consistent across study design. However, data combined from case-control studies revealed a statistically significant positive trend (P = 0.001) in the risk of premenopausal breast cancer for women exposed to oral contraceptives for longer duration. This risk was predominant among women who used oral contraceptives for at least 4 years before their first term pregnancy (relative risk = 1.72; 95% confidence interval = 1.36 to 2.19). Additional study is required to determine whether this finding in a subgroup of exposed women is confirmed and whether the risk remains increased with advancing age.     

Oral contraceptives,menopausal estrogens,and the risk of breast cancer: A case-control study in greece

In a hospital-based case-control study in Athens, we examined the association between the use of oral contraceptives and menopausal estrogens and the risk of breast cancer. Eight hundred and twenty patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to the cases by age and interviewer. The data were modeled through logistic regression, controlling for demographic and reproductive variables. Odds ratio patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not elevated among ever-users of oral contraceptives, regardless of age at diagnosis of breast cancer, duration of oral contraceptive use or timing of use in relation to first full-term pregnancy. Among peri- and post-menopausal women who ever used menopausal estrogens, with never-users as the baseline, a statistically significant elevated odds ratio was found after adjusting for age at menopause. © 1995 Wiley-Liss, Inc.     

Breast cancer and combined oral contraceptives: An Italian case-control study

The risk of breast cancer in relation to use of oral contraceptives was evaluated using data from a hospital-based case-control study from Northern Italy on 1517 cases below age 60 and 1351 controls admitted for acute diseases unrelated to any of the known or potential risk factors for breast cancer. The multivariate relative risk for ever vs. never users was 1.3 (95% confidence interval = 1.0–1.7). However, the risk was not related to duration of use: indeed the highest risk was observed among short-term users (<2 years), and the point estimate was 0.9 among users for 5 years or more. The elevated risk among short-term users, if not due to residual confounding or selection mechanisms, is probably explainable in terms of recall bias (i.e. more careful report of short or very short use by cases). No definite pattern was observed in relation to latency or recency of use, and the point estimates were 0.8 for women who had ever used the pill before age 25 and 0.8 for those who had ever used the pill before first full-term pregnancy. Thus, the study presents further reassuring information on the oral contraceptive/breast cancer debate. Its major limitation lies in the low prevalence of oral contraceptive users in Italy, with a consequently reduced statistical power, although, with the number of cases involved, it was possible to exclude a relative risk of 1.4 for long-term use or for ever use before first birth.     

Oral contraceptives and breast cancer in northern Italy. Final report from a case-control study.

To assess the relation between oral contraceptive (OC) use and breast cancer, we analysed data from a case-control study conducted in Northern Italy between 1983 and 1991 on 2,309 cases below age 60 and 1,928 controls admitted to hospital for acute diseases unrelated to OC use and to any of the known or potential risk factors for breast cancer. OC use was reported by 16% of cases and 14% of controls. The multivariate relative risk (RR) for ever vs never use of combination OC was 1.2 (95% confidence interval (CI) 1.0-1.4). However, there was no trend in risk with duration. The RR was elevated for very short use, but declined to 0.8 (95% CI = 0.5-1.0) for five or more years'' use. No noteworthy relationship was found for other major measures of OC use, although RR estimates were above unity for women who had stopped use less than 5 years before (RR = 1.5, 95% CI = 1.1-2.0), started use less than 10 years before (RR = 1.3, 95% CI = 1.0-1.9), started when 25 or more years old (RR = 1.4, 95% CI = 1.1-1.7), or after first birth (RR = 1.2, 95% CI = 1.0-1.5). No interaction was observed between OC use and family history of breast cancer, parity and age at first birth. A separate analysis of 373 cases and 456 control below age 40 showed no association with ever use (RR = 0.9, 95% CI = 0.6-1.2).     

Oral contraceptives and breast cancer risk in Taiwan,a country of low incidence of breast cancer and low use of oral contraceptives

One hundred and seventy four (81% of all) pathologically confirmed new incident cases of female breast cancer identified from a medical center in Taipei from February, 1993 to June, 1994 were selected as the case group. Four hundred and fifty three inpatient controls who were without obstetric-gynecological, breast, or malignant diseases were individually matched for each case by age and date of admission. Information was obtained through direct interview and review of medical records. Conditional logistic regression was used to estimate the effects of each risk factor. After adjusting for education level, body mass index, age at menarche and first full-term pregnancy, parity, menopausal status and age at menopause, lifetime lactation, use of lactation inhibition hormones, and family history of breast cancer, breast cancer risk significantly elevated in use of OC before 25 years old and before 1971. In stratified analysis, significantly higher risk were found in OC use before 25 years old and in duration of use less than one year among post-menopausal subjects. Our results support the notion that OC use in early life for younger women and in early calendar years increase breast cancer risk. Int. J. Cancer 77:219–223, 1998.© 1998 Wiley-Liss, Inc.     

Oral contraceptives and breast cancer. A review with some comments on mathematical models.

The relationship between oral contraceptive use and breast cancer is discussed on the basis of information given in review articles, meta-analyses and editorials emphasizing methodological problems related to bias and confounding. Over the last few years a shift in opinion has taken place. Most reviewers now consider that long-term use of oral contraceptives is associated with an increased risk of premenopausal breast cancer and no effect among postmenopausal breast cancer. This result is compatible with an additive effect (in rate measure scale) of oral contraceptive use on breast cancer risk.     

Oral contraceptives and primary liver cancer

The relative risk for developing primary liver cancer in northern Italian users of oral contraceptives, compared to matched controls was calculated based on reported cases in hospitals in the greater Milan area from 1984-1987. The incidence of and mortality from primary liver cancer, as well as the prevalence of oral contraceptive usage, have both been rising to Italy since the late 1950s. 21 cases of liver cancer, in women aged 32-59 (median 50), occurred in the Milan area during the study period. These women, and 145 controls matched for age but admitted to hospitals for a variety of non-neoplastic diseases, were interviewed with a structured questionnaire covering socio-demographics, life style, diet, medical history, and history of use of oral contraceptives and other drugs. 19.0% of the cases had used oral contraceptives compared to 7.6% of controls, a relative risk of 1.8 for up to 5 years' use, and 8.3 for 5 years. History of hepatitis was associated with 14% of cases and 7% of controls. Italians have a higher incidence of liver neoplasms that northern Europeans and Americans, probably because of higher incidence of risk factors, such as hepatitis and alcohol use. The attributable risk for oral contraception, however, is lower in this population.