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.     

Alcohol and colorectal cancer: a case-control study from northern Italy

The role of alcohol consumption in the etiology of colorectal cancer has been investigated in a case-control study conducted from 1985 to 1990 in the northern part of Italy, on 889 cases of colon cancer, 581 cases of rectal cancer, and 2,475 controls admitted to hospital for acute, non-neoplastic, nodigestive disordes. After allowance for age, education, study center, body mass index, and approximate total energy intake, no significant associations between alcohol intake and the risk of cancer of the colon or rectum were found (odds ratios [OR] for 42 drinks/week cf none =1.0 (95 percent confidence interval [CI]=0.8–1.4) and 0.7 (CI=0.5–1.0) for cancer of the colon and rectum, respectively). A significant increase in the risk of colon cancer with increasing alcohol consumption was, however, observed in females (OR for 28 drinks/week cf none = 1.8 (CI=1.1–3.0)). While the results of the present case-control study do not suggest that alcohol plays a role in the etiology of colon or rectum cancer overall, they provide a hint for a weak association between alcohol consumption and colon cancer among females which, because of the similarities with breast cancer, should be evaluated in the context of the possible relationship between colon cancer, alcohol intake, and female hormones.Drs Barra, Franceschi, and Guarneri, are with the Epidemiology Unit, Aviano Cancer Center Aviano, Italy. Dr Franceschi is also with the European Cancer Prevention Organisation (ECP), Epidemiology and Cancer Working Group, Brussels, Belgium. Drs Negri and La Vecchia are with the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also with the Institute of Social and Preventive Medecine, University of Lausanne, Lausanne, Switzerland. Address correspondence to Dr Barra, Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ., 33081 Aviano (PN) Italy. Support for this project was contributed by the Italian Association for Research on Cancer and the Italian League against Tumors, Milan and the Italian National Research Council (CNR Applied Project Clinical Applications of Oncological Research).     

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.     

Breast cancer and alcohol consumption: a case-control study in northern Italy

From 1983 to 1986, a population-based case-control study of alcohol and breast cancer (250 cases and 499 controls) was conducted in a grape-farming area of northern Italy, where wine consumption is widespread. In the study population, 30% of women were abstainers and 15% reported alcohol intakes of 30 g/day or more. After adjustment for potential confounders, no appreciable association was evident for alcohol consumptions as high as 40 g/day. Women reporting intakes of more than 40 g/day showed approximately a 2-fold increase in the risk of breast cancer (relative risk, 1.9; 95% confidence interval, 1.1-3.3). A 2-fold increase in risk was observed for consumptions of more than 40 g/day of alcohol from wine, the most common alcoholic beverage in this population. These findings suggest that an association between alcohol intake and breast cancer may exist. However, the moderate risk observed seems to be limited to the relatively small group of women consuming daily amounts of alcohol in excess of 40 g, the equivalent of about half a bottle of wine or more.     

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.     

Benign breast disease and breast cancer: a case-control study in a cohort in Italy

Sixty-two cases of invasive breast cancer were identified in a large cohort of women previously treated for biopsy-proven benign breast disease (BBD) at the Breast Unit of CSPO, in Florence, along with a group of 315 controls, strictly matched by age and year of diagnosis. A pathologist reviewed and reclassified all the original BBD slides according to recently proposed criteria (no evidence of epithelial proliferation, epithelial proliferation without or with atypia). Information about potential confounding factors was collected during personal interviews. In comparison to the women with "non-proliferative" BBD, women classified as having "proliferative disease without atypia" showed a weak and non-significant increase in risk (OR 1.3; 95% CI: 0.5-3.5). In contrast, women with "atypical hyperplasia" were at very high risk of developing breast cancer (OR 13.0; 95% CI: 4.1-41.7). When planning mammography screening or other large-scale early-diagnosis programmes for breast cancer in the general female population, follow-up of high-risk subgroups of BBD patients should be considered.     

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.     

A case-control study of diet and gastric cancer in northern Italy

Dietary factors in the aetiology of stomach cancer were investigated using data from a case-control study conducted in Northern Italy on 206 histologically confirmed carcinomas and 474 control subjects in hospital for acute, non-digestive conditions, unrelated to any of the potential risk factors for gastric cancer. Dietary histories concerned the frequency of consumption per week of 29 selected food items (including the major sources of starches, proteins, fats, fibres, vitamins A and C, nitrates and nitrites in the Italian diet) and subjective scores for condiments and salt intake. Pasta and rice (the major sources of starch), polenta (a porridge made of maize) and ham were positively related with gastric cancer risk, whereas green vegetables and fresh fruit as a whole (and specifically citrus fruit) and selected fibre-rich aliments (such as whole-grain bread or pasta) showed protective effects on gastric cancer risk. Allowance for major identified potential distorting factors (chiefly indicators of socio-economic status) reduced the positive association with pasta or rice consumption, but did not appreciably modify any of the other risk estimates. When a single logistic model was fitted including all food items significant in univariate analysis, the 3 items remaining statistically significant were green vegetables (relative risk, RR = 0.27 for upper vs. lower tertile), polenta (RR = 2.32) and ham (RR = 1.60). Indices of beta-carotene and ascorbate intake were negatively and strongly related with gastric cancer risk, but the association with these micronutrients was no longer evident after simultaneous allowance for various food items. An approximately 7-fold difference in risk was found between extreme quintiles of a scale measuring major positive and negative associations.     

Height and cancer risk in a network of case-control studies from northern Italy

The relationship between self-reported height and cancer risk was investigated in an integrated series of case-control studies including 273 cases of cancer of the oesophagus, 474 of the stomach, 558 of the colon, 352 of the rectum, 227 of the liver, 267 of the pancreas, 110 of the larynx, 2,388 of the breast, 545 of the cervix uteri, 563 of the endometrium, 688 of the ovary, 80 of the prostate, 263 of the bladder, 105 of the kidney, 43 Hodgkin's disease, 152 non-Hodgkin's lymphomas, 109 multiple myelomas, and a total of 5,574 controls admitted to hospital for acute, non-neoplastic conditions. No significant positive trend in risk was observed for any of the cancer sites considered, and some suggestion of elevated risks for the upper quintile of height was observed only for prostate (relative risk, RR = 1.4), kidney (RR = 2.7) and colon (RR = 1.2) in males (but not in females). For breast cancer, all the RRs for subsequent quintiles of height were close to unity. Four neoplasms showed significant inverse trends with height: oesophagus (RR = 0.7 for highest vs. lowest quintile), cervix (RR = 0.4), endometrium (RR = 0.7) and ovary (RR = 0.6). For oesophagus and cervix the trends could be explained, at least in part, in terms of social class correlates (multivariate RR 0.8 and 0.5, respectively), while for endometrium they could possibly be related to an inverse correlation between height and body mass (multivariate RR 0.9). Thus, our study did not support the hypothesis that nutrition in childhood and adolescence (which in this population is a determinant of adult height) is directly related to the subsequent risk of cancer at several major cancer sites. A number of inverse associations emerged, which may be either spurious and incidental, or suggest that poorer nutrition early in life may be an unfavourable indicator of the subsequent risk of selected neoplasms.     

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.     

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 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 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.     

Vitamin D intake and breast cancer risk: a case-control study in Italy

Background: Vitamin D has been suggested to play a protectiverole against several cancers, including breast cancer. Patients and methods: We used data from a case–controlstudy conducted in Italy from 1991 to 1994 to study the relationbetween dietary intake of vitamin D and breast cancer risk.Subjects were 2569 women with incident, histologically confirmedbreast cancer and 2588 hospital controls. Odds ratios (ORs)and 95% confidence intervals (CIs) according to deciles of vitaminD intake were estimated by multiple logistic regression models. Results: After allowance for major risk factors for breast cancerand dietary covariates including calcium and energy intake,there was no association with vitamin D up to the seventh decile.Thereafter, the OR declined, so that the overall trend was statisticallysignificantly inverse. The OR for subjects in the three highestdeciles of consumption compared with those in the lowest onescombined was 0.79 (95% CI 0.70–0.90). Intake of vitaminD >3.57 µg or 143 IU appeared to have a protectiveeffect against breast cancer. The inverse association was consistentacross strata of menopausal status. Conclusions: This study adds to the existing evidence that vitaminD intake in inversely associated with breast cancer risk. Key words: breast cancer, case–control study, risk factors, vitamin D Received for publication October 30, 2007. Revision received May 5, 2008. Accepted for publication July 9, 2008.     

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 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.