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 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

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.     

Progestogen-only oral contraceptives and risk of breast cancer in New Zealand

Little is known about the influence of progestogen-only contraceptives on a woman's risk of breast cancer. This issue was examined in a national population-based case-control study in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. Use of progestogen-only pills was reported by 8.7 percent of all control subjects (and by 17.3 percent of those aged 25 to 34 years). The relative risk (RR) of breast cancer in women who had ever used progestogen-only pills was estimated to be 1.1 (95 percent confidence interval [CI]=0.73–1.5). In women aged 25 to 34 years, the RR was 2.3 (CI=1.2–4.3). Women who had started using progestogen-only pills within the last 10 years were at increased risk of breast cancer (RR=1.6, CI=1.0–2.4), whereas those who had first used them earlier were at significantly reduced risk (RR=0.44, CI=0.22–0.90). These findings are similar to results for depot medroxyprogesterone acetate, and a possible analogy with the influence of pregnancy is also suggested.The anthors are with the Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand. Address correspondence to: Dr Skegg, Department of Preventive and Social Medicine, University of Otago Medical School, P. O. Box 913, Dunedin, New Zealand. This research was supported by grants from the Medical Research Council of New Zealand and from the Special Program of Research, Development, and Research Training in Human Reproduction, World Health Organization.     

Use of oral contraceptives, alcohol, and risk for invasive breast cancer.

The aim of our study was to examine how the use of oral contraceptives (OCs) interact with alcohol on breast cancer risk within the large prospective follow-up study, Norwegian Women and Cancer Study. Between 1991 and 1997, women aged 30 to 70 years were drawn at random from the central person register and mailed an invitation. Follow-up information was collected throughout 2001 by linkage to national registries. Only women (n = 86,948) with complete information on alcohol consumption and duration of OC use were included in the present analysis. A total of 1,130 invasive breast cancers were diagnosed during 618,638 person-years of follow-up. Consumption of > or =10.0 g/d alcohol was associated with a breast cancer relative risk (95% confidence interval) of 1.69 (1.32-2.15), consistent with a linear relationship (P for trend < 0.0001). Among alcohol consumers, an excess risk of breast cancer was observed for total duration of OC use only among women who consumed <5 g/d alcohol (P for trend = 0.0009). We observed a negative interaction between duration of OC use and alcohol consumption effects (P for interaction = 0.01). After stratification on menopausal status, the association between high alcohol intake and breast cancer was more prominent among postmenopausal women than among premenopausal women (P for heterogeneity = 0.01). No interaction between alcohol and duration of OC use were significant after stratification on menopausal status. Our findings in conjunction with biological data imply that alcohol and OCs have antagonistic effects on breast cancer risk through a common pathway. Whether the interactive effect differs according to menopausal status remains unclear and needs further investigations.     

Use of oral contraceptives and risk of breast cancer in young women

Many studies have shown that oral contraceptive (OC) use increases a young woman's risk of breast cancer, although some studies suggest that the risk may be limited to recent use. The objective of this study was to determine what particular aspects of OC use could be important for breast cancer development at an early age in the cohort of women who had the opportunity to use OCs all of their reproductive life. The cases were first diagnosed with breast cancer at age 40 or younger between 1983 and 1988, and identified by the Los Angeles County Cancer Surveillance Program. Control subjects were individually matched to participating cases on birth date (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Detailed OC histories were obtained during in-person interviews with subjects. In general the risk estimates were small, and not statistically significant. Compared to no use, having used OCs for 12 years or more was associated with a modest non-significant elevated breast cancer risk with an odds ratio (OR) of 1.4 (95% confidence interval (CI)=0.8–2.4). Long-term (12 years or more) users of high-dose estrogen pills had a non-significant 60% higher breast cancer risk than never users (CI=0.9–3.2). Early use was associated with slightly higher ORs among young women (age 35), and among parous women. Recent use was associated with somewhat higher ORs among parous women and women above age 36. Analyses by stage, body weight, and family history yielded similar results. This study is consistent with a modest effect of early OC use on breast cancer risk in young women.     

Long-term use of oral contraceptives and risk of invasive cervical cancer

To evaluate the relationship between use of oral contraceptives and risk of invasive cervical cancer, a case-control study involving 479 patients and 789 population controls was undertaken in 5 geographic regions of the US. Initially, the relationship was obscured by confounding variables, particularly the interval since last Pap smear. Control for this variable as well as for sexual and sociodemographic factors revealed an RR of 1.5 overall, with long-term users (5 or more years) being at a 2-fold higher risk than non-users. Pill associations prevailed for both adenocarcinomas and squamous-cell tumors, and risks were highest for those using pills containing high estrogen potencies. In addition, there was some evidence that pill associations were most pronounced among women who had never used barrier methods of contraception or who had histories of genital infections, suggesting that oral contraceptives may act as co-carcinogens with transmissible agents. Our findings provide further evidence that long-term use of oral contraceptives may have a carcinogenic effect on cervical epithelium, but emphasize the need for careful evaluation of confounding influences.     

Oral contraceptives and colorectal cancer risk: a meta-analysis

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69-0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72-0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74-0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30-0.71). A better understanding of this potential relation may help informed choice of contraception.     

Risk of breast cancer associated with short-term use of oral contraceptives

Objective To estimate breast cancer risk associated with short-term (<6 months) oral contraceptive use, and explore variation in estimates by use characteristics and medical, menstrual, and reproductive history. Methods We analyzed data from the Women’s Contraceptive and Reproductive Experiences Study. Case subjects were white women and black women, 35–64 years old, diagnosed with invasive breast cancer in July 1994–April 1998. Control subjects identified by random-digit dialing were matched to case subjects by age, race, and study site. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Overall, short-term oral contraceptive use was not associated with breast cancer risk (OR = 1.0; 95% CI = 0.8–1.1). However, significant interaction between short-term use and menopausal status led to an observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI = 1.0–1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6–1.0) associated with short-term use. The association was more pronounced in women with non-contraceptive reasons for use and underlying risk factors for breast cancer. Conclusions These associations may result from underlying characteristics of users or unmeasured factors influencing duration of use and breast cancer risk. The majority of the work on this paper was completed while Dr. Berlin was a Professor of Biostatistics at the University of Pennsylvania. Robert Spirtas is retired.     

Oral contraceptives and breast cancer risk in BRCA1 and BRCA2 mutation carriers

Estrogen and progestin in oral contraceptives may be carcinogenic to the breast, and their use has been associated with a modest increase in the risk of breast cancer in the general female population. Women who carry deleterious mutations in breast cancer susceptibility genes, BRCA1 and BRCA2, have a significantly higher risk of breast and ovarian cancer. The literature on the role of oral contraceptives in carriers is sparse and the results are inconclusive. Findings from some case-control studies and the International BRCA1/2 Carrier Cohort Study suggest that oral contraceptive use may be associated with an increased risk of breast cancer in BRCA1 and BRCA2 carriers. Understanding the potential effects of oral contraceptive use among carriers has important implications for preventive strategies and clinical management. Both the possible protective effect for ovarian cancer risk and the increased potential risk of breast cancer must be considered.     

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 the risk of endometrial cancer

The relationship between the use of combbination oral contraceptives (OCs) and the risk of endometrial cancer was assessed in a case-control study conducted in the Swiss Canton of Vaud between 1 January 1988 and 31 July 1990. Subjects included 122 women aged 75 or less with histologically confirmed endometrial cancer, and 309 control women in hospital for acute conditions unrelated to OC use. Overall, 14 percent of cases and 27 percent of controls had ever used OCs, corresponding to a multivariate relative risk (RR) of 0.5 (95 percent confidence interval [CI]: 0.3. 0.8). The risk of endometrial cancer was found to be related inversely to duration of OC use: RR=1.0 for less than two years of OC use; 0.5 for two to five years; and 0.3 (95 percent CI: 0.1, 0.7) for more than five years. The protection appeared greater within 20 years since last use, and the RR rose to 0.8 after 20 or more years since last use; numbers are too small, however, for reliable inference from these subanalyses. No significant interaction or modifying effect was observed with other major factors related to endometrial cancer, including parity, body mass index, estrogen replacement therapy, and cigarette smoking. While this study provides further evidence for the protective effect of OCs against risk of endometrial cancer, the relationship requires continued evaluation to assess the long-term implications and public health impact of OC use.This work was supported in part by the Swiss National Science Foundation Grant No. 3.866-0.88.     

Hormonal content and potency of oral contraceptives and breast cancer risk among young women

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.     

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.