A nested case-control study and meta-analysis 4 assessed breast cancer risk associated with current or recent use of different types of hormonal contraceptives. 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 matched controls. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined (OR 1.23, 95% CI 1.14 to 1.32; p < 0.001), oral progestagen-only (OR 1.26, 95% CI 1.16 to 1.37; p < 0.001), injected progestogen (OR 1.25, 95% CI 1.07 to 1.45; p = 0.004), or progestagen-releasing intrauterine devices (LNG-IUS) (OR 1.32, 95% CI 1.17 to 1.49; p < 0.001). The meta-analyses yielded raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral (RR 1.29, 95% CI1.21 to 1.37; p = 0.2), injected (RR 1.18, 95% CI 1.07 to 1.30; p = 0.004), implanted (RR 1.28, 95% CI 1.08 to 1.51; p = 0.06), and IUD (RR 1.21, 95% CI 1.14 to 1.28p = 0.1).
A meta-analysis 5 including 6 observational studies with a total of 261 221 women assessed the risk of breast cancer in LNG-IUS users. Two subgroup analyses were performed for different study designs. The breast cancer risk was not increased neither in cohort studies (RR 0.80, 95% CI 0.57 to 1.11, n=190 475, I²=92%, P=0.18 > 0.05) nor in case‒control studies (OR 1.38, 95% CI 0.98 to 1.94, n=70 746, I²=94%, P=0.06 > 0.05). However, the heterogeneity was high.
A systematic review 6 included 10 studies (6 cohort studies, 3 case-control studies and 1 systematic review/meta-analysis). 6 found a positive association between breast cancer and the use of LNG-IUS. One study only found an increased risk for invasive breast cancer in the subgroup of women aged 40-45 years. In contrast, 3 studies showed no indication of a higher risk.
A systematic review 1 including 54 studies with a total of 53,297 women with breast cancer and 100 239 women without breast cancer, was abstracted in DARE. Prospective studies and case-control studies with at least 100 women with breast cancer were included.
For women currently taking combined oral contraception (COC) and for 10 years after stopping there was a small increase in the relative risk of breast cancer: current users 1.24 (95% CI 1.15 to 1.33), 1 - 4 years after stopping COC 1.16 (95% CI 1.08 to 1.23), 5 - 9 years after stopping 1.07 (95% CI 1.02 to 1.13). More than 10 years after stopping the relative risk was 1.0. The cancers diagnosed in women who had used oral COC were less advanced clinically than those diagnosed in never-users. The relative risk of tumours that had spread beyond the breast compared with localized tumours in ever-users compared with never-users was 0.88 (95% CI 0.81 to 0.95).
Another systematic review 2 estimating association between oral contraceptive use and breast cancer included 44 trials (case-control and cohort sudies). Breast cancer incidence was slightly but significantly increased in users (OR 1.08; 95% CI 1.00 to 1.17: 23 trials, over 450 000 women). Results show a higher risk associated with more recent use of oral contraceptives: 0-5 years since use (OR 1.21; 95% CI 1.04 to 1.41); 5-10 years (OR 1.17; 95% CI 0.98 to 1.38); 10-20 years since use (OR 1.13; 95% % CI 0.97 to 1.31); over 20 years (OR 1.02; 95% CI 0.88 to 1.18). There was no time-dependent relationship as a function of duration of use.
A systematic review and meta-analysis 3 included 42 case-control studies with a total of 110 580 women (30 778 into the breast cancer [BrCa] group and 79 802 into the control group, of which 15 722 and 38 334 were using OC, respectively). The use of OC was associated with a increased risk of BrCa in general, OR = 1.15, 95% CI 1.01 to 1.31, p = 0.0358. Other risk factors found for BrCa, were early menarche, nulliparous, non-breastfeeding, older age at first parity, postmenopause, obesity, smoking, and family history of BrCa.
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