Any type of hormonal contraceptive could increase the risk of developing breast cancer, with progestogen-only hormonal contraceptives, compared with the oestrogen-progestogen only pill, resulting in a 20%-30% higher risk, according to findings from the Clinical Practice Research Datalink (CPRD).
The researchers also concluded that because the underlying risk of breast cancer increases with 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.
The study team had analysed data from 9 488 women who developed invasive breast cancer between the ages of 20 and 49, and 18 171 closely matched women without breast cancer.
Among participants, 44% of those with breast cancer and 39% without it had been prescribed a hormonal contraceptive an average of three years before diagnosis.
Overall, the absolute excess risk of developing breast cancer over a 15-year period in women with five years of use ranged from eight in 100 000 women for use from age 16 to 20, to 265 in 100 000 for use from the ages of 35 to 39.
Previously, reports The Independent, studies found that the combined contraceptive pill – combining oestrogen and progestogen – was linked to a relatively small increase in the risk of developing breast cancer. This increase declines after the patient stops using it.
In 2018, one study identified a 50% increased breast cancer risk among participants who had started taking a combined oral contraceptive pill within the previous 12 months.
However, said Gillian Reeves, professor of statistical epidemiology and director of the Cancer Epidemiology Unit, University of Oxford, there’s little to indicate that women taking contraception need to make any changes.
In fact, the benefits of taking contraceptives beyond preventing pregnancy – including protecting against endometrial cancer and ovarian cancer – might outweigh the negatives of taking the pill.
“The main purpose of doing this research was really to fill a gap in our knowledge,” Reeves said.
“We’ve known for many years that combined oral contraceptives, which women have been using for decades, also have an effect on breast cancer risk, a small increase, which is transient.
“We weren’t absolutely sure what the corresponding effect of these progestogen-only contraceptives would be.
“What we’ve shown is that they’re just the same in terms of breast cancer risk, and seem to have a very similar effect to the other contraceptives and the effect we’ve known about for many years.”
Breast Cancer Now notes that the study, published in PLOS Medicine, did not factor in whether a family history of the disease contributed to risk levels among participants.
“The study didn’t look at what hormonal contraceptives the women may have used in the past or consider how long they may have been on the progestogen-only contraception,” said Dr Kotryna Temcinaite, head of research communications at Breast Cancer Now.
“Further work is needed to help us fully understand the impact of using this type of contraception.”
Breast Cancer UK says 56 000 new cases of breast cancer are recorded in the UK each year. It’s the most common form of cancer, with about one out of every eight women being diagnosed with it during their lifetime.
Study details
Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case–control study and meta-analysis
Danielle Fitzpatrick, Kirstin Pirie, Gillian Reeves, Jane Green, Valerie Beral.
Published in PLOS Medicine on 21 March 2023
Abstract
Background
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.
Methods and findings
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.
Conclusions
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.
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