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 percent higher chance of developing breast cancer” among women who used intrauterine devices (IUDs). While that’s technically mostly true, it doesn’t tell the whole story and can be grossly misinterpreted.
These influential headlines come from a large Danish cohort study published in JAMA that evaluated breast cancer incidence in first-time users of LNG-IUDs like Mirena compared to birth-year-matched non IUD users. The study took place from 2000 to 2019 and enrolled patients aged 15-49 years (average age 38). The type or stage of breast cancers developed over the study period was not reported, although already having a breast cancer diagnosis was an exclusion criterion. An important difference in this study compared to a similar previous study was that this one evaluated the cumulative risk of breast cancer with the 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 news agencies got the “40 percent higher risk” that made numerous headlines). Additionally, the risk of breast cancer increased with longer duration of LNG-IUD. The reported HR was 1.3 with under five years of use, 1.4 with five to 10 years of use, and 1.8 with 10-15 years of use. The baseline risk of developing breast cancer in nonusers was 1.1 percent. Therefore, these hazard ratios translate to 14 excess breast cancer diagnoses per 10,000 users with zero to five years of use, 29 with five to 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 percent higher chance of developing breast cancer”- that phrasing suggests relative risk, but what was 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 is the danger of reporting relative risk without reporting baseline risk, as the singular mention of a relative risk of 40 percent can be wildly misinterpreted.
By way of comparison, the relative risk of developing breast cancer in people taking combined oral contraceptives 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 oral contraceptives has been reported to be 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, combined oral contraceptives, and the delay of a 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 mention the slightly higher risk of breast cancer when discussing birth control options with patients, but please approach it differently than saying there is a “40 percent increased risk of breast cancer” with IUDs. Reporting relative risk without the context of baseline or absolute risk can be extremely misleading.
For more information, see the topic Intrauterine Device (IUD) in DynaMedex.
Reference: JAMA. 2024 Nov 12;332(18):1578-1580
