Pills, patches, implants, and injections — the various forms of hormonal birth control have different formulations and doses of estrogen, progestin, or both. One might think, then, that they may have an unequal influence on breast cancer risk, but a new study in PLOS Medicine on Tuesday suggests that’s not so. The analysis found that most forms of hormonal birth control, regardless of their formulation, seem to confer roughly the same, small increase to breast cancer risk.
“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 did not work on the study.
Hormonal birth control can contain estrogen and progestin or progestin alone and work by preventing the release of eggs from the ovaries, thickening cervical mucus, and thinning the endometrium. These hormones are also important to the formation and growth of the majority of breast cancers, so researchers have studied how hormonal birth control might alter one’s breast cancer risk.
“There was always a concern that oral contraceptives might affect breast cancer risk,” said Gillian Reeves, the director of the cancer epidemiology unit at the University of Oxford and one of the investigators on the study. “But a lot of the studies were done decades ago. There was a big study done in 1996 that showed a transient risk existed, and it declined after women stopped taking it.”
In that paper, a meta-analysis of 54 studies, women had about a 25% increased risk of breast cancer while they were on the pill compared to people who had not taken the pill. That amounts to a rather slight absolute increase of roughly 0.15% for women under the age of 40 and 0.5% for women under the age of 50. That risk diminished the longer women were off the contraceptive, entirely fading away after about 10 years.
The issue is that in the 1990s, the combination pill containing both estrogen and progestin was the main oral contraceptive. Today, progestin-only options like the minipill or the intrauterine device proliferate. “After that 1996 study, we didn’t know much about the effects of other kinds of contraceptives,” Reeves said.
So, Reeves and her colleagues wanted to see if any of the modern hormonal birth control offerings made any difference in breast cancer risk. To do the study, they gathered data from a large primary care database in the United Kingdom called the Clinical Practice Research Datalink and analyzed all breast cancer cases between 1996 and 2017. Then, they matched those cases with women who did not have cancer at a similar age and same general practice clinic and compared their prescription histories for contraceptives.
Reeves found that women who took any kind of hormonal contraceptive also had a relative increased risk of breast cancer of about 20% to 30% while they were on it. “That was a combined oral, progestin only injection, IUD, whatever,” Reeves said. In absolute terms, also as in past studies, that translates to an absolute increase of about half a percent for women under the age of 50. “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 added. “So, the modern, newer forms of hormonal contraceptives behave pretty much the same as we’ve been using for decades.”
The exception may be for people who already have an elevated risk of breast cancer due to certain pathogenic mutations or a family history of breast cancer. For these individuals, a 20% to 30% increase in cancer risk may translate to higher absolute odds of getting breast cancer, although Reeves cautioned that there’s less research done specifically on groups of women with high-risk mutations and hormonal contraceptives.
The study throws into question the assumption that more local applications of progestin like IUDs might be less likely to contribute to breast cancer risk, Westhoff said. That may make the decision to use hormonal contraception a little bit more complicated for people who are concerned about an already elevated breast cancer risk. “It’s going to be surprising to people that the IUD is associated with the same risk. I think some people might be upset with this paper because they thought they would get away from that risk with the IUD,” she said.
The study also raises a bit of a biological puzzle. All of the various hormonal contraceptives are vastly different from one another. “Their dose and biological effects are quite different. That’s what’s fascinating — they’re all so different, but end up with the same relative risk,” Westhoff said. “So, it’s like — why?”
So far, neither this study nor any others have answered that question, leaving Westhoff with some reservations. For one, studies have shown that women who are on contraceptives tend to be diagnosed at earlier stages if they get cancer. “That suggests there may be some bias. Maybe women using hormones are in more routine contact with health professionals and thus are more likely to be diagnosed a little earlier,” Westhoff said. “The incidence curve of breast cancer is so steep that a slightly earlier diagnosis of the same cases could explain the whole odds ratio.”
If that’s true, Westhoff said, then it’s possible that hormonal contraceptives don’t have any impact on breast cancer at all. But even if they do, Westhoff added it’s important to weigh all the pros and cons of hormonal contraceptives. Studies have shown that hormonal contraceptives tend to have a protective effect against ovarian and endometrial cancer, and they’re very successful at their raison d’être: preventing pregnancy.
“The U.S. has the highest rate of maternal mortality out of any developed country, and it’s an outrage,” Westhoff said. “The No. 1 way we can reduce maternal mortality is birth control. The pill is safer than giving birth.”