Findings on potential interactive effects of oral contraceptives (OCs) and hormone replacement therapy (HRT) on breast cancer risk have been inconsistent. We aimed to use population-based cohort data to determine whether former use of OCs affects breast cancer risk among HRT users, taking into account regimens of HRT, duration and currency of use.
Methods
The cohort consisted of 16 928 Icelandic women who visited the Icelandic Cancer Detection Clinic in 1979-2006 and provided information on use of OCs and HRT when they were 48 years or older. By record linkage to the Icelandic Cancer Registry, all breast cancer diagnosed during follow-up was identified. Using Cox regression, hazard ratios (HRs) for breast cancer according to hormone use were estimated, adjusting for menstrual and reproductive risk factors. Also, interaction analyses were carried out.
Results
Breast cancer risk was significantly increased among ever users of combined estrogen and progestin (EP-HRT) preparations (HR=2.61; 95% CI 2.00-3.41) and not among users of estrogen-only regimens (E-only HRT) (HR=1.13; 95% CI 0.85-1.49). Ever users of both OCs and HRT had higher breast cancer risk than users of only one of the two (HR=2.19; 95% CI 1.67-2.87). After restricting the analysis to EP-HRT and focusing on long-term and current use, there was an indication of a negative interaction with ever OC use (p=0.06); HR=2.87; 95% CI 1.79-4.60 for never OC users and HR=2.24; 95% CI 1.51-3.34 for former OC users.
Conclusion
After taking HRT regimen, duration and currency of use into account, the results of our population-based cohort study do not support the notion that former OC use increases breast cancer risk among HRT users, on the contrary there was an indication of a slightly lower risk in former OC users, restricted to current, long-term EP-HRT users.
oral contraceptives hormone replacement therapy breast cancer risk cohort, combined estrogen progestin HRT breast cancer Iceland, former OC use HRT breast cancer interaction, estrogen-only vs combined HRT breast cancer risk, population-based cohort oral contraceptive breast cancer postmenopausal, current long-term EP-HRT breast cancer hazard ratio, hormone replacement therapy duration breast cancer Icelandic women, oral contraceptive ever use breast cancer risk postmenopausal, sequential hormone exposure OC HRT breast malignancy, progestin HRT breast cancer risk population cohort
PMID 24460068 24460068 DOI 10.3109/0284186X.2013.878471 10.3109/0284186X.2013.878471
Cite this article
Þorbjarnardóttir, Þ., Ólafsdóttir, E. J., Valdimarsdottir, U., Olafsson O, & Tryggvadottir, L. (2014). Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older. Acta oncologica (Stockholm, Sweden), 53(6), 752-758. https://doi.org/10.3109/0284186X.2013.878471
Þorbjarnardóttir Þ, Ólafsdóttir EJ, Valdimarsdottir U, Olafsson O, Tryggvadottir L. Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older. Acta Oncol. 2014;53(6):752-758. doi:10.3109/0284186X.2013.878471
Þorbjarnardóttir, Þuríður, et al. "Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older." Acta oncologica (Stockholm, Sweden), vol. 53, no. 6, 2014, pp. 752-758.
The incidence and survival of breast cancer (BC) vary across countries. This study aimed to determine risk factors for BC and estimate the overall survival rate in BC patients of the Golestan Cohort Study (GCS). This case-control study was performed among participants of the GCS. Cases (N = 99) consisted of women who were diagnosed with BC and controls (n = 400) were selected out of women participating in the same cohort and had not developed any cancer during the follow-up period. Controls were frequency matched to case on both place of residency and 5-year categories of age. Considering confounding variables, logistic regression analysis manifested a reverse association between parity and BC (OR [odds ratio] = 0.87, 95% CI: 0.80-0.95, P = 0.001). In addition, we found women who had family history of any cancer (OR = 1.63, 95% CI: 1.02-2.60, P = 0.04) and long term oral contraceptive (OCP) use (≥10 years) (OR = 3.17, 95% CI: 1.27-7.95, P = 0.01) were at higher risk of BC. Of the total patients, 23 (23.2%) were died due to BC after a mean follow-up of 102.4 ± 5.31 months. Using the Kaplan-Meier analysis, the 5-year survival in these patients was 74%. In the Golestan Cohort population, long term OCP use and family history of cancer were risk factors for BC, while parity was a protective factor. The 5-year survival of BC patients in the GCS is still lower relative to Europe and the United States.
Contraception/ComparisonBreast Cancer RiskBRCA1 Mutation CarriersHereditary Breast Cancer
Kotsopoulos J et al., 2014·Breast Cancer Res Treat
It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.
General OB/GYNReproductive Risk FactorsBreast Cancer RiskCancer Epidemiology
Clinical, animal, and epidemiological studies have clearly demonstrated that cancer is a hormonally mediated disease and several factors that influence hormonal status or are markers of change in hormonal status have been shown to be associated with the risk of breast cancer. To identify the association of various reproductive factors with breast cancer. A hospital-based, matched, case-control study. Three hundred and twenty newly diagnosed breast cancer cases and three hundred and twenty normal healthy individuals constituted the study population. The subjects in the control group were matched individually with the cases for their age ± 2 years and socioeconomic status. A pre-tested, semi-structured questionnaire was administered to each individual to collect information on identification data, socio-demographic profile, and reproductive factors. The Chi-square test and unpaired t-test were used. The conditional univariate logistic regression analysis (unadjusted odds ratio and confidence intervals) was used to calculate the significance level of each variable followed by multivariate regression analysis. The cases had a lower mean age at menarche, higher age at marriage, higher mean age at last child birth, lower mean duration of breastfeeding, higher number of abortions, late age at menopause, history of oral contraceptive pills, and a family history of breast cancer as compared to the controls. The results of the present study revealed a strong association of reproductive factors with breast cancer in the Indian population.
Contraception/ComparisonBreast Cancer RiskHormonal Risk FactorsProspective Cohort Studies
Zhu H et al., 2012·Eur J Contracept Reprod Health Care
It has been suggested that taking oral contraceptives (OCs) may increase breast cancer incidence. However, data in this regard are inconsistent. We performed this meta-analysis to estimate the association between OC use and breast cancer risk. Prospective cohort studies on OC use and breast cancer risk were identified by searching databases from the period 1960 to 2012. Results from individual studies were synthetically combined using STATA 11 software. A total of 13 prospective cohort studies were included in our meta-analysis, involving 11,722 cases and 859,894 participants. The combined relative risk (RR) of breast cancer for evercompared with never-OC users was 1.08 (95% confidence interval [CI]: 0.99-1.17). Dose-response analysis based on five eligible studies showed that every ten-years' increment of OC use was associated with a significant 14% (95% CI: 1.05-1.23) rise in breast cancer risk. Little evidence of publication bias was found. This meta-analysis provides evidence of a non-significant increase in breast cancer risk associated with ever OC use, but the risk for long-term OC users is significantly greater. However, the latter finding is based on only a limited number of studies.