Reference: JAMA. 2024 Nov 12;332(18):1578-1580
Practice Point: Use of levonorgestrel intrauterine device (LNG-IUD) is associated with a small but slightly higher risk of developing breast cancer compared to nonuse, similar to the breast cancer risk associated with combined oral contraceptive (COC) use or delay of pregnancy until after age 30.
EBM Pearl: Reporting relative risk without the context of baseline or absolute risk can be extremely misleading.
Many clinicians find themselves routinely providing second opinions after Dr. Google these days. The hazard of consuming misinformation gets even higher when public reporting agencies go for shock value, such as recent CNN and ABCNews reports about a study that showed a “40% higher chance of developing breast cancer” among women who used IUDs. While that’s technically mostly true, it doesn’t tell the whole story and obviously can be grossly misinterpreted by many (or most) people.
This cherry-picked headline comes from a large Danish cohort study recently published in JAMA that evaluated incident breast cancer in first-time initiators of LNG-IUDs like Mirena compared to birth-year-matched nonusers. The study took place from 2000-2019 and enrolled patients 15-49 years old (average age 38). The type or stage of breast cancer was not reported, although having breast cancer was an exclusion criterion so one might assume that a majority were early-stage breast cancers. An important difference in this study compared to a very similar previous study was that this one evaluated cumulative risk of breast cancer with time-varying continuous use of the LNG-IUD over the study period.
The study authors reported that during a mean follow-up of 6.8 years, LNG-IUD use was associated with an increased risk of breast cancer compared to nonuse of hormonal contraceptives, with an overall adjusted hazard ratio (HR) of 1.4 (95% CI 1.2-1.5). (This [1.4] is the data point where the news agencies got the “40% higher risk.” More on that in a minute). The risk of breast cancer increased with longer duration of LNG-IUD, with reported HR 1.3 with 0-5 years of use, HR 1.4 with > 5-10 years of use, and HR 1.8 with > 10-15 years of use. The baseline risk of developing breast cancer in nonusers was 1.1%. Therefore, these hazard ratios translate to 14 excess breast cancer diagnoses per 10,000 users with 0-5 years of use, 29 with > 5-10 years of use, and 71 with > 10-15 years of use.
From the perspective of causality, it’s important to remember that this was an observational study and it’s plausible that some unknown variable was at play. For instance, are patients who present for IUD insertion more likely to undergo breast cancer screening and therefore be more likely to be diagnosed with breast cancer?
Getting back to the “40% higher chance of developing breast cancer”- that phrasing suggests relative risk. What were actually reported were hazard ratios. While the two are related, they are not the same. A hazard ratio is a rate of occurrence over a period of time and is often used in survival studies. Relative risk is the probability of an event in exposed vs. nonexposed groups. Perhaps more important, however, is the danger of reporting relative risk without reporting baseline risk, as the singular mention of a relative risk of 40% can be wildly misinterpreted.
By way of comparison, the relative risk of developing breast cancer in people taking COCs has been reported at 1.2, with an excess of 13 events per 100,000 person-years. When it comes to venous thromboembolism, the relative risk in people taking COCs has been reported at 3.5. And—get this—delaying pregnancy until after age 30 is also associated with an increased risk of developing breast cancer, with a relative risk of 1.2 compared to nulliparous persons.
The point is: LNG-IUDs, COCs, and the delay of first pregnancy until after age 30 all carry a comparable risk for developing breast cancer. The risk is low but not wholly insignificant. Let’s not forget, however, that the risk of maternal morbidity and mortality due to pregnancy is higher than any of the risks we have talked about here. How information is presented matters. A lot. Many people make important decisions based on a single piece of information, or misinformation as it were. With all this in mind, clinicians should definitely mention the slightly higher risk of breast cancer when discussing birth control options with patients, but for the love of Pete, please approach it differently than saying there is a “40% increased risk of breast cancer” with IUDs.
For more information, see the topic Intrauterine Device (IUD) in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.