The current study, reported in the PLOS Medicine journal, explored breast cancer risk linked to the current or past use of hormonal contraception during the reproductive period in women.
Study: Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case–control study and meta-analysis. Image Credit: PATCHARIN SIMALHEK / Shutterstock
Oral contraception is reported to be a highly effective method of birth control and is used globally. However, a recent study looked at the risk of breast cancer associated with the use of Combined oral contraceptives (COCs) and progesterone-only contraception (POC).
COCs containing both estrogen and progesterone are prescribed in most circumstances, rather than the progesterone-only option. Earlier studies have shown that using COCs can be associated with a slight increase in breast cancer risk. However, that risk is alleviated a decade following cessation of use. POP use is rising, but not much is known about this risk due to the low prevalence of use hitherto.
The data used in this study was obtained from the Clinical Practice Research Datalink (CPRD), a UK database acquired from primary care practitioners.
The scientists compared the presence of prescriptions for hormonal contraceptives in approximately 9,500 women under 50 years who developed invasive breast cancer between 1996 and 2017, with over 18,000 controls. All cases and controls had clinical data available for a mean of seven years prior to the diagnosis of cancer.
Over three-quarters of the cases were in women between 40 and 49, with a fifth being in those aged 30-39 years and only 2% in those under 30 years.
The results from this database were amalgamated with those of earlier studies on POC from January 1995 to November 2022. This was done to arrive at a stronger association, if present, given the paucity of data in any single study.
What did the study show?
The researchers found that 44% of breast cancers in this cohort were associated with the use of a hormonal contraceptive. On average, the prescription date was three years before the diagnosis. Additionally, 39% of controls also had a hormonal contraceptive prescription an average of 3 years before cancer diagnosis. In both situations, half the prescriptions were for POC.
There was a rise in breast cancer risk with all types of hormonal contraception, viz., COCs, oral POC, injectable POC, or progesterone-releasing intrauterine devices (PIUDs). The increase with the first three was by about a quarter. In contrast, the risk was 32% with the PIUD.
Risk was raised by the current or recent use of all POC forms, ranging from about 20% higher with injectable POC or PIUDs, to a 30% increase with oral or implanted POC.
The meta-analysis included 12 older studies alongside the current cohort, allowing a 15-year follow-up period to be examined. Consequently, this also showed a higher risk of breast cancer with five years of POC or COC use in high-income countries over the 15-year follow-up.
Compared to the expected rates, there was an excess of breast cancer cases by 8/100,000 in women between the ages of 16 and 20 years, but 61/100,000 between 25 and 29 years. Strikingly, there were 265 excess cases per 100,000 women between 35 and 39 years.
Interestingly, the levonorgestrel-releasing PIUD is associated with a comparable increase in breast cancer risk, despite the much lower serum levels of this hormone following the use of this POC mode compared to other forms.
Unfortunately, there is no data available on the prior use of COCs. As a result, it is impossible to arrive at any conclusions about the association of breast cancer with hormonal contraception over the long term or how the duration of use is related to breast cancer risk.
What are the implications?
POC now makes up half of all hormonal contraception prescriptions in the UK, making it important to understand its risks. The current study shows an increase in the risk of breast cancer with hormonal contraception, irrespective of the presence of estrogen or the mode of use.
Injectable, implantable, or oral forms of progesterone, as well as progestogen-releasing intrauterine devices, are alike linked to a similar level of increased risk.
The risk-benefit ratio concerning breast cancer risk would seem to favor the use of oral contraceptives earlier in life (16-20 years) rather than in the fourth decade when the absolute excess of cases associated with oral contraception rises by a factor of 40 – increasing by 265 cases per 100,000 women.
This amounts to an increase in breast cancer risk from 0.084% to 0.093% with hormonal contraception in the earlier period but from 2% to 2.2% in the years between 35 to 39 years.
A careful appraisal of the risks would appear to be mandatory while considering hormonal contraceptive use during the latter half of the reproductive period, considering their benefits on women's health.