Study finds similar association of progestogen-only and combined hormonal contraceptives with breast cancer risk

There is a relative increase of 20% to 30% in breast cancer risk associated with both combined and progesterone-only contraceptives, whatever the mode of delivery, though with five years of use, the 15-year absolute excess incidence is at most 265 cases per 100,000 users. The results appear in a new study publishing March 21^st in the open access journal PLOS Medicine by Kirstin Pirie of University of Oxford, UK, and colleagues.

Use of combined oral contraceptives, containing both estrogen and progestogen, has previously been associated with a small increase in breast cancer risk but there is limited data about the effect of progestogen-only hormonal contraceptives. However, the use of progestogen-only contraceptives has increased substantially in recent years, with almost as many prescriptions in England for oral progestogen-only contraceptives as for combined oral contraceptives in 2020.

In the new study, researchers analyzed data from a UK primary care database, the Clinical Practice Research Datalink (CPRD), on 9,498 women under the age of 50 with invasive breast cancer diagnosed in 1996-2017, as well as data on 18,171 closely matched controls.

On average, 44% of women with breast cancer and 39% of matched controls had a hormonal contraceptive prescription, with about half the prescriptions being for progestogen-only preparations. With five years use of either oral combined or progestogen-only contraceptives, the associated 15-year absolute excess incidence of breast cancer was estimated at 8 cases per 100,000 hormonal contraceptive users at age 16-20 years and 265 cases per 100,000 users at age 35-39 years. The odds of breast cancer were similarly and significantly raised, regardless of whether the contraceptive used was a combined (estrogen and progestogen) oral preparation (OR=1.23 95%CI 1.14-1.32, p<0.001), a progestogen-only oral preparation (OR= 1.26 95% CI 1.16-1.37, p<0.001), an injected progestogen (OR= 1.25 95% CI 1.07-1.45, p=0.004), or a progestogen releasing intra-uterine device (OR=1.32 95% CI 1.17-1.49, p<0.001). These results were combined with those from previous studies from high income countries, which included women from a wider age range.

Pirie adds, “These findings suggest that current or recent use of all types of progestogen-only contraceptives is associated with a slight increase in breast cancer risk, similar to that associated with use of combined oral 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 will be smaller in women who use it at younger rather than at older ages,” the authors state. “These excess risks must, however, be viewed in the context of the well-established benefits of contraceptive use in women's reproductive years.”

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In your coverage, please use this URL to provide access to the freely available paper in PLOS Medicine: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004188

Citation: Fitzpatrick D, Pirie K, Reeves G, Green J, Beral V (2023) Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case–control study and meta-analysis. PLoS Med 20(3): e1004188. https://doi.org/10.1371/journal.pmed.1004188

Author Countries: United Kingdom, Australia

Funding: Central data collection, checking, analysis, and manuscript preparation (DF, KP, GR, JG, VB) was supported by the core funding of the Cancer Epidemiology Unit by Cancer Research UK (C570/A16491 and A29186) and the Medical Research Council (MR/K02700X/1). DF was funded through the Rhodes Trust. The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript.