A new study published Tuesday in PLOS Medicine found that different forms of hormonal birth control containing estrogen, progestin, or a combination of both are associated with a slight increase in breast cancer risk.

Study details and key findings

Until recently, birth control research primarily centered on the combination pill containing both estrogen and progestin since it was the main oral contraceptive available on the market.

Now, there are a variety of progestin-only options available. The authors conducted the study to learn more about the effect modern hormonal birth control offerings have on breast cancer risk, merging their results with those of 12 previous studies to "bring together the totality of the available evidence."

For the study, researchers conducted a meta-analysis and nested case-control study of data on hormonal contraceptive prescriptions from the U.K. Clinical Practice Research Datalink. They analyzed data for 9,498 women under the age of 50 who were diagnosed with invasive breast cancer between 1996 and 2017, and they looked at 18,171 matched controls.

On average, 44% of those with breast cancer and 39% of matched controls were taking a hormonal contraceptive prescription of 3.1 years before they were diagnosed with breast cancer. Roughly half of the prescriptions were progestin-only formulations.

According to study author Kirstin Pirie of the University of Oxford and colleagues, the increased risk started to decline after oral contraceptive use ceased, decreasing from 33% when prescribed in the past year, to 17% when prescribed one to four years prior, and to 15% when prescribed five or more years earlier.

In addition, the study authors estimated that the absolute excess risk of developing breast cancer during a 15-year period in those with five years of oral contraceptive use spanned 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.

Overall, Gillian Reeves, study author and director of the cancer epidemiology unit at the University of Oxford, said they found that women who took any kind of hormonal birth control had a relative increased risk of breast cancer of roughly 20% to 30% while they were on it. "That was a combined oral, progestin only injection, IUD, whatever," Reeves said. That translates to an absolute increase of around half a percent for those under the age of 50.

The authors noted that the study was limited by a lack of available prescription data for the period before subjects entered the database. This made it difficult to evaluate the long-term effects of hormonal contraceptive use, but "it does not unduly affect estimates of the short-term effects of such use, which is the main focus of these investigations," according to the study authors.

Commentary

Ultimately, the researchers' analysis found that most forms of hormonal contraceptives, regardless of their formulation, seem to share a similar, small increase to breast cancer risk. "So, the modern, newer forms of hormonal contraceptives behave pretty much the same as we've been using for decades," Reeves said.

"It's kind of interesting and strange that all of these different hormonal contraceptives with or without estrogen have an increased risk so close to each other," said Carolyn Westhoff, an obstetrician and contraceptives researcher at Columbia University who was not involved the study.

"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. "Women who are most likely to be using contraception are under the age of 50, where the risk of breast cancer is even lower."

"We're talking about a risk that acts on women in their 20s and 30s, when we have a very low background risk. So, 20 to 30% of something that's very small is still very small," Reeves 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," Pirie said. (Chen, STAT+ [subscription required], 3/21; Bassett, MedPage Today, 3/22; Fitzpatrick et al., PLOS Medicine, 3/21)