Progestin-Only Birth Control Linked to Small Increase in Breast Cancer Risk

Current or recent use of progestin-only contraceptives was associated with a small increase in risk of breast cancer, similar to the risk associated with combined hormonal contraceptives, according to a nested case-control study and meta-analysis from the U.K.

In the nested case-control study of data from the Clinical Practice Research Datalink, women had a comparable increased risk of breast cancer regardless of whether their last hormonal contraceptive prescription was for:

• Oral combined: OR 1.23 (95% CI 1.14-1.32, P<0.001)
• Oral progestin-only: OR 1.26 (95% CI 1.16-1.37, P<0.001)
• Injected progestin: OR 1.25 (95% CI 1.07-1.45, P=0.004)
• Progestin-releasing intrauterine devices (IUDs): OR 1.32 (95% CI 1.17-1.49, P<0.001)

This increased risk declined after oral contraceptive use was discontinued, dropping from 33% when the contraceptives were prescribed within the last year, to 17% when last prescribed 1 to 4 years ago, and to 15% when last prescribed 5 or more years ago, reported Kirstin Pirie, MSc, of the University of Oxford in England, and colleagues in PLOS Medicine.

Pirie’s group also estimated that the absolute excess risk of developing breast cancer over a 15-year period in women with 5 years of oral contraceptive use ranged from eight in 100,000 women for use from ages 16 to 20, to 265 in 100,000 for use from ages 35 to 39.

“Combined and [progestin]-only hormonal contraception can increase the risk of breast cancer, but the risk is small,” said Claire Knight, senior health information manager at Cancer Research UK, in a press release. “Women who are most likely to be using contraception are under the age of 50, where the risk of breast cancer is even lower.”

In the press release, Pirie said, “Given that a person’s underlying risk of developing breast cancer increases with advancing age, the absolute excess risk of breast cancer associated with either type of oral contraceptive will be smaller in women who use it at younger ages. These excess risks must, however, be viewed in the context of the well-established benefits of contraceptive use in women’s reproductive years.” These include a reduction in the risk of ovarian cancer.

Pirie and team noted that previous research showed that the use of combined estrogen and progestin is associated with a small increase in the risk of breast cancer that declines after stopping use. However, the use of progestin-only contraceptives has substantially increased in recent years.

Since few studies have reported on the risks associated with progestin-only contraceptive use, Pirie and colleagues conducted a meta-analysis combining their results with those of 12 previous studies to “bring together the totality of the available evidence.”

The meta-analysis showed significantly increased relative risks (RRs) for current or recent use of progestin-only contraceptives:

• Oral progestin-only: RR 1.29 (95% CI 1.21-1.37, P=0.2)
• Injected progestin: RR 1.18 (95% CI 1.07-1.30, P=0.004)
• Implanted progestin: RR 1.28 (95% CI 1.08-1.51, P=0.06)
• Progestin-releasing IUDs: RR 1.21 (95% CI 1.14-1.28, P=0.1)

For their study, Pirie and colleagues used data on hormonal contraceptive prescriptions recorded in the Clinical Practice Research Datalink, a U.K. primary care database, for 9,498 women under the age of 50 who had invasive breast cancer diagnosed from 1996 to 2017, as well as 18,171 matched controls.

Overall, 44% of women with breast cancer and 39% of matched controls had a hormonal contraceptive prescription an average of 3.1 years before breast cancer diagnosis (or equivalent date for controls), without about half of the prescriptions being progestin-only preparations.

Pirie and team noted that their study was limited by the fact that prescription data were unavailable in the period before the women entered the database. While this made it difficult to assess the long-term effects of hormonal contraceptive use, “it does not unduly affect estimates of the short-term effects of such use, which is the main focus of these investigations,” they wrote.