October 16, 2024

expert reaction to breast cancer in users of Levonorgestrel-Releasing Intrauterine Systems

A study published in JAMA looks at the use of Levonorgestrel-Releasing Intrauterine Systems and breast cancer risk. 

Prof Amy Berrington, de Gonzalez, Professor of Clinical Cancer Epidemiology, The Institute of Cancer Research, said:

Does the press release accurately reflect the science?

“Yes

Is this good quality research? are the conclusions backed up by solid data?
“Yes, the study uses high-quality registry data for a large general population. The details on the methods are somewhat limited because it’s only being published as a research letter, but the connection to the previous study in Nejm 2017, which used similar registries and included a more detailed description of the methods, provides additional reassurance.

How does this work fit with the existing evidence?
“The findings are consistent with those of previous studies that show a small increased risk of breast cancer for current users of hormonal contraceptives.

Have the authors accounted for confounders? are there important limitations to be aware of?
“They accounted for key confounders such as number of pregnancies and use of other hormonal contraceptives. They do not find a clear dose-response of increasing risk with increasing duration of use and note that this could be due to the smaller number of women who used this type of IUD for more than 10 years, or because some women had the IUD removed and this was not captured in the registry data. As a dose-response relationship can increase our confidence that the finding isn’t due to unknown confounders, they also acknowledge that unknown confounders can’t be excluded, but the consistency with previous studies of hormonal contraceptives makes this less likely, in my opinion.

What are the implications in the real world? is there any overspeculation?
“I think they are cautious with their interpretation. This is another type of hormonal contraceptive that likely increases breast cancer risk.

Is the excess risk of breast cancer in levonorgestrel-releasing ius users found (14/10,000 females) a worrisome/large figure?
“It is a small risk that should be considered along with the benefits from the contraceptive. The risk is likely even smaller for younger women because their risk of breast cancer is even lower.

How does this figure compare to data on the associated risk of breast cancer from taking daily oral contraceptive?
“The risk is similar in magnitude to other hormonal contraceptives.

What are implications of the findings of this study on females in the UK?
“Women should be aware that most types of hormonal contraceptive are associated with a small increased risk of breast cancer. This study adds another type of hormonal contraceptive to that list. That has to be considered with the many benefits from hormonal contraceptives.”

Dr Channa Jayasena, Reader in Reproductive Endocrinology, Imperial College London, said:

The Levonorgestrel-Releasing Intrauterine Systems (LNG-IUS) is a highly effective form of contraceptive for women. Unlike contraceptive pills, LNG-IUS releases a progesterone-like hormone directly into the womb.  This means that levels of the hormone are much lower than when you take it as a tablet. It is well known that prolonged use of the contraceptive pill slightly increases breast cancer risk. However, we have always assumed that the LNG-IUS would not increase breast cancer risk due to the much lower levels of hormone exposure to the whole body. The results of this study are therefore highly unexpected. A large population of women taking LNG-IUS was compared with a similar sized population of women not taking any contraceptive medication. While the researchers tried to make sure that the two populations of women were matched for things like age, weight and education, other behaviours like smoking have not been measured. So, women not taking contraceptive medication may have been healthier in other ways compared to the LNG-IUS group.

The study found that there were 14 extra cases of breast cancer per 10,000 women in the group using LNG-IUS compared to those not using contraceptive medication. It is difficult to tell how this compares with taking the contraceptive pill which has been studied in different populations. It is unfortunate that this study did not compare breast cancer risk between the LNG-IUS and oral contraceptive pill. But it is important that smoking, alcohol and obesity are much more important risk factors for breast cancer than contraceptive medications.

We always need to be vigilant to new health risks from medical treatments, and this is no exception. My advice for women is that breast cancer risk caused by LNG-IUS is not established but warrants a closer look.”

Dr Mangesh Thorat, Honorary Reader in Wolfson Institute of Population Health, Queen Mary University of London and Consultant Breast Surgeon, Homerton University Hospital, Queen Mary University of London (QMUL), said:

“This new large Danish study adds to the existing literature evaluating the risk of breast cancer in women using hormonal forms of contraception. The study specifically investigated the use of hormonal intrauterine devices, commonly known as hormonal coils, for example – Mirena coil. Similar to the British study (Fitzpatrick and colleagues) published last year, this study shows a small increase in the risk of breast cancer associated with the use of such coils. The existing evidence suggests that the increase in the risk is similar to that with oral contraceptive use. It is worth noting that this association has been known for at least a few years and a broad consensus exists among the medical fraternity that the overall benefits of hormonal contraception outweigh the harms like such small increase in the risk of developing breast cancer. Furthermore, as the baseline risk of breast cancer is lower in younger individuals, any increase in the risk associated with the use of hormonal coil is also smaller. The risk increases with increasing age and it is reasonable for women near 40 years of age to have a discussion with their healthcare practitioner regarding non-hormonal modes of contraception.”

‘Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems’ by Mørch et al. was published in JAMA at 16:00 UK time on Wednesday 16^th October 2024. 

DOI: 10.1001/jama.2024.18575

Declared interests

Dr Channa Jayasena: “No Conflicts to Declare”

Dr Mangesh Thorat: “No Conflicts to Declare”

For all other experts, no reply to our request for DOIs was received.