Menopausal oestrogens and breast cancer risk: an expanded case-control study

A study among 1960 post-menopausal breast cancer cases and 2258 controls identified through a nation-wide screening program enabled evaluation of effects of oestrogen use on breast cancer risk. Ever use was not associated with increased risk (RR = 1.0), but a significant trend was observed with increasing years of use, with users of 20 or more years being at a 50% excess risk. Elevations associated with long-term use were apparent across all menopause subgroups (natural, ovaries retained, ovaries removed). Hormones exerted particularly adverse effects in those initiating use subsequent to a diagnosis of benign breast disease, particularly long-term users (RR = 3.0, 95% CI 1.6-5.5). There was also some indication that effects predominated among the lower stage tumours, an observation similar to that observed for endometrial cancer. These findings support a role for oestrogens in the aetiology of breast cancer, although risk appears to be enhanced only after extended periods of use, and not to the extent observed for other hormonally-sensitive tumours.     

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: 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.     

Combined oral contraceptives containing chlormadinone acetate and breast cancer: results of a case-control study.

The main subject of this hospital-based case-control study was the possible relationship between use of combined oral contraceptives (OCs) containing chlormadinone acetate and breast cancer. Analyses were based on data from 490 cases with newly diagnosed breast cancer and 1,223 controls and were separately performed for combined OCs with and without chlormadinone. For either of the combined OCs, risk was not elevated in ever users, did not increase with duration of use and did not change with time since initial exposure or with time since most recent use. However, the relative risk was increased in current users: RR = 1.72 (0.88, 3.36) for combined OCs with chlormadinone and RR = 1.42 (1.01, 2.00) for combined OCs without chlormadinone, which is, however, explained as a screening effect. These results show that chlormadinone as a constituent of combined OCs does not influence breast cancer risk.     

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: A cooperative Italian study

The relationship between oral contraceptives (OC) and breast-cancer risk was analysed using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centres on 1,991 patients below age 65 with histologically confirmed incident breast cancer and 1,899 controls admitted to hospital for a wide range of acute, non-neoplastic, nonhormone-related diseases. “Ever OC use” was reported by 18% of cases versus 14% of controls, corresponding to a multivariate odds ratio (OR) of 1. 1 (95% confidence interval, CI 0.9 to 1.4). The ORs were 1.3 for use lasting < 1 year, 1. 1 for 1 to 4 years, 0.9 for 5 to 8 years, and 1.2 for over 8 years. With reference to age at first use, there was some indication that the OR was elevated in women who had started use before age 30, but not in those starting at a later age. With reference to time since last OC use, the OR was above unity for women who had stopped for less than 10 years (1.6 for 1 to 4 years; 1.7 for 5 to 9 years), but the OR declined to unity for women who had stopped OC use for 10 years or longer. The OR for women who had stopped OC use for less than 10 years was consistently elevated across strata of selected covariates, and was directly related to the duration of use (OR 1.3 for < 5 years, 1.7, for ≥5 years). In contrast, the OR was 0.6, for use lasting ≥ 5 years in women who had stopped for 10 years or more. The elevated OR for women who had recently stopped OC use, together with the absence of association (or the suggestion of some protection) for those who had stopped for 10 years or more is consistent with the pattern of breast-cancer risk observed after a full-term pregnancy, and provides important reassurance on a public health level on the long-term impact of OCs on breast carcinogenesis. © 1995 Wiley-Liss, Inc.     

Oral contraceptives and cancers of the breast and of the female genital tract. Interim results from a case-control study

We analysed data from a case-control investigation conducted in Milan, Northern Italy, to evaluate the relation between the use of combination oral contraceptives and the risk of cancers of the breast, ovary, endometrium and cervix uteri. For the present analysis, 776 cases of histologically confirmed breast cancer, 406 of epithelial ovarian cancer and 170 of endometrial cancer aged under 60 were compared with a group of 1,282 subjects below age 60 admitted for a spectrum of acute conditions apparently unrelated to oral contraceptive use or to any of the known or potential risk factors for the diseases under study. Likewise, 225 cases of invasive cervical cancer were compared with 225 age-matched inpatient controls, and 202 cases of cervical intra-epithelial neoplasia with 202 outpatient controls identified in the same screening clinics. The age-adjusted relative risk estimates for ever vs. never use of combination oral contraceptives were 1.04 (95% confidence interval (CI) 0.73-1.37) for breast cancer, 0.68 (95% CI = 0.48-0.97) for epithelial ovarian cancer, 0.50 (95% CI = 0.23-1.12) for endometrial cancer, 1.49 (95% CI = 0.88-2.55) for cervical cancer and 0.77 (95% CI = 0.50-1.18) for cervical intra-epithelial neoplasia. The risk of ovarian cancer decreased and that of invasive cervical cancer increased with longer duration of use. Neither duration of oral contraceptive use nor time since first or last use significantly altered a user's risk of other neoplasms considered. Likewise, analysis of sub-groups of age, parity or other potentially important covariates did not show any important interaction, and allowance for them by means of logistic regression did not materially modify any of the results. These data confirm that combination oral contraceptives confer some protection against ovarian and endometrial cancers but may increase the risk of invasive cervical cancer if used for several years, and indicate that the past or current pattern of oral contraceptive use in Italy is unlikely materially to affect the risk of breast cancer.     

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.     

Dietary fiber, beta-carotene and breast cancer: results from a case-control study

To study the association between dietary fiber, beta-carotene and breast cancer, the average daily intake of these dietary components was compared among 133 incident breast cancer cases and 238 population controls. Average daily intake of cereal products, fruit and vegetables was also studied. A statistically significant lower energy-adjusted intake of dietary fiber was observed in cases than in controls (mean +/- SD: 25.4 +/- 6.7 g vs. 27.7 +/- 7.4 g, 95% confidence interval (CI) of the age-adjusted difference = -3.8, -0.8). Intake of beta-carotene was similar for cases and controls. The multivariate adjusted odds ratio (OR) of breast cancer among women in the highest quartile of intake of cereal products, as compared to those in the lowest quartile, was 0.42 (95% CI = 0.19-0.92) and the trend was statistically significant (p = 0.03). The corresponding OR for intake of dietary fiber was 0.55 (95% CI = 0.26-1.17) but the trend was not significant. The OR for the highest quartile of intake of beta-carotene, fruit, vegetables, and all vegetable products combined was less than unity, but there was no significant inverse trend. These results suggest that a high intake of cereal products, especially those rich in fiber, may be inversely related to incidence of 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.     

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.     

Non-Hodgkin's lymphoma and farming: an expanded case-control study

A previously published case-control study of agricultural risk factors involved male cases of non-Hodgkin's lymphoma registered under code 202 of the International Classification of Diseases (ICD). This study has been expanded with the inclusion of cases registered under ICD code 200, and additional controls. The expanded study comprises 100 ICD 200 cases and 83 ICD 202 cases registered during the period 1977-81, together with 338 controls selected from other cancer registrations during the same period. The largest relative risk for specific farming types was for orchard workers (odds ratio = 3.7, 90% confidence limits 1.1-12.1). No elevated risks were observed for exposure to farm animals, nor for potential exposure to phenoxy herbicides (odds ratio = 1.0, 90% confidence limits 0.7-1.5), or chlorophenols (odds ratio = 1.4, 90% confidence limits 0.8-2.3). The previous finding of an excess risk associated with fencing work was weakly supported by the expanded study (odds ratio = 1.4, 90% confidence limits 1.0-2.0). However, the previous finding of an excess risk associated with meat works employment was more strongly supported (odds ratio = 1.8, 90% confidence limits 1.2-2.6). One relevant risk factor is 2,4,6-TCP which is used in the treatment of pelts, but the excess risks do not appear to be confined to pelt department workers. An alternative hypothesis is that meat workers may be exposed to oncogenic viruses.     

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.