Recent oral contraceptive (OC) use has been consistently associated with increased risk of breast cancer, but evidence on specific breast cancer subtypes is sparse.
Methods
We investigated recency and duration of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from the African American Breast Cancer Epidemiology and Risk Consortium. The study included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043 with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors, which do not have receptors for estrogen, progesterone, and human epidermal growth factor 2), and 10,044 controls. Multivariable polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for exposure categories relative to never use, controlling for potential confounding variables.
Results
OC use within the previous 5 years was associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR 1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer. The risk declined after cessation of use but was apparent for ER+ cancer for 15 to 19 years after cessation and for ERbreast cancer for an even longer interval after cessation. Long duration of use was also associated with increased risk of each subtype, particularly ER-.
Conclusions
Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ERbreast cancer, is needed.
oral contraceptives breast cancer subtypes, African American breast cancer epidemiology, hormonal contraception breast cancer risk, triple-negative breast cancer oral contraceptives, AMBER consortium breast cancer, estrogen receptor status contraceptive use, molecular subtype breast cancer risk, racial disparities breast cancer, recency duration oral contraceptive exposure, case-control breast cancer African American women
PMID 25849024 25849024 DOI 10.1186/s13058-015-0535-x 10.1186/s13058-015-0535-x Bethea et al. 2015, Bethea 2015
Cite this article
Bethea, T. N., Rosenberg, L., Hong, C. C., Troester, M. A., Lunetta, K. L., Bandera, E. V., Schedin, P., Kolonel, L. N., Olshan, A. F., Ambrosone, C. B., & Palmer, J. R. (2015). A case-control analysis of oral contraceptive use and breast cancer subtypes in the African American Breast Cancer Epidemiology and Risk Consortium. Breast cancer research : BCR, 17(1), 22. https://doi.org/10.1186/s13058-015-0535-x
Bethea TN, Rosenberg L, Hong CC, Troester MA, Lunetta KL, Bandera EV, et al. A case-control analysis of oral contraceptive use and breast cancer subtypes in the African American Breast Cancer Epidemiology and Risk Consortium. Breast Cancer Res. 2015;17(1):22. doi:10.1186/s13058-015-0535-x
Bethea, T. N., et al. "A case-control analysis of oral contraceptive use and breast cancer subtypes in the African American Breast Cancer Epidemiology and Risk Consortium." Breast cancer research : BCR, vol. 17, no. 1, 2015, pp. 22.
Related articles
gynecology/breast-health/breast-cancer-riskcontraception/oral-contraceptives/cancer-risk
Open Access
Beaber EF et al., 2014·Cancer Epidemiol Biomarkers Prev
Evidence suggests that recent oral contraceptive (OC) use is associated with a small increased breast cancer risk; yet risks associated with contemporary OC preparations and by molecular subtype are not well characterized. We conducted a population-based case-control study of invasive breast cancer among women ages 20 to 44 residing in the Seattle-Puget Sound area from 2004 to 2010 (985 cases and 882 controls). We collected information on contraceptive use and participant characteristics via an in-person interview. Multivariable-adjusted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Lifetime duration of OC use for ≥ 15 years was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.1-2.2). Current OC use (within 1 year of reference date) for ≥ 5 years was associated with an increased risk (OR, 1.6; 95% CI, 1.1-2.5) and there were no statistically significant differences in risk by OC preparation. Risk magnitudes were generally greater among women ages 20 to 39, and for estrogen receptor-negative (ER(-)) and triple-negative breast cancer (current use for ≥ 5 years among ages 20-39: ER(-) OR, 3.5; 95% CI, 1.3-9.0; triple-negative OR, 3.7; 95% CI, 1.2-11.8), although differences between groups were not statistically significant. Long-term use of contemporary OCs and current use for ≥ 5 years was associated with an increased breast cancer risk among women ages 20 to 44. Risk may be greater among younger women and for ER(-) and triple-negative breast cancer, but these findings require confirmation. Continued surveillance and pooled analyses of OC use and breast cancer risk by molecular subtype are needed as OC preparations evolve.
gynecology/breast-health/breast-cancer-riskcontraception/oral-contraceptives/cancer-risk
Open Access
Hunter DJ et al., 2010·Cancer Epidemiol Biomarkers Prev
Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear. We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001. During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted for the excess risk: the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001). Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk. Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change.
Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.
To extend knowledge about the long-term use of hormones in hormone therapy or oral contraception as prognostic factors in breast cancer. The MCC-Spain project is a cohort of 1,685 women with incident breast cancer recruited in Spain. Recruitment was carried out between 2007 and 2010, and the follow-up finished in December 2017. The impact of hormone therapy or oral contraception on breast cancer prognosis was analyzed considering year of birth and menopausal status (1,095 women [65%] were postmenopausal). Hazard ratios (HRs) were estimated using Cox regression models. Death by any cause was considered as the event, and hormone therapy or oral contraception were analyzed as regressors. Oral contraception use for less than 5 years shows an HR of 1.10 (95% CI, 0.75 to 1.62), whereas use for 5 or more years shows an HR of 1.46 (95% CI, 0.95 to 2.25), with a P trend of 0.01, showing a dose-dependent response. Regarding hormone therapy and restricting the analysis to postmenopausal women born between1940 and 1959, where most hormone therapy (consumption) is concentrated, the results did not show any trend. Concerning oral contraception use, our results demonstrate that their use is related to poor prognosis in breast cancer. However, research in this field is limited and controversial, indicating the need for more research in this area. Regarding hormone therapy consumption, our results indicate no association with better prognosis, which contradicts what has previously been published.