Published: 13-04-2016 10:02 | Updated: 13-04-2016 12:39

Potential effects of fertility treatments on breast density and cancer risk

Infertility and hormonal fertility treatments may influence the amount of dense tissue in the breast, a risk factor for breast cancer, according to a study at Karolinska Institutet published in the open access journal Breast Cancer Research.

The researchers selected 43313 women aged between 40 and 69 years, who had mammograms as part of the KARMA project between 2010 and 2013. Out of 8963 women who reported fertility problems, 1576 had undergone controlled ovarian stimulation (COS), 1,429 had had hormonal stimulation without COS and 5,948 had received no fertility treatment.

Denser breasts

The researchers found that women with a history of infertility had denser breasts than other women. The association was more pronounced in women who had undergone COS, the hormone treatment required for in vitro fertilization. While this may indicate a potential adverse effect of COS on breast density, the researchers point out that the effect may be due to the underlying infertility that motivates the use of a specific treatment, rather than to the treatment itself.

Frida Lundberg, doctoral student at the Department of Medical Epidemiology and Biostatistics, and lead author of the study, said:

– The results from our study indicate that infertile women, especially those who undergo COS, might represent a group with an increased breast cancer risk. While we believe it is important to continue monitoring these women, the observed difference in breast tissue volume is relatively small and has only been linked to a modest increase in breast cancer risk in previous studies.

Breast tissue is composed of two types of tissue: dense, fibroglandular and non-dense, fatty tissue. Women with extremely dense breasts have a four to six fold higher risk of developing breast cancer than women with non-dense breasts, previous research has found.

Self-reported information

In this study, women with a history of infertility were found to have higher absolute dense volume – that is more dense, fibroglandular breast tissue – than non-infertile women. Among infertile women, those who had undergone COS had higher absolute dense volume than those who had not received any hormone treatment.

To assess associations between infertility, hormonal fertility treatments and mammographic density, the researchers first compared mammographic density levels between fertile and infertile women. They then compared infertile women who had never received hormonal fertility treatment to those who had.

As this study relied on self-reported information and it was not possible to capture specific diagnoses from the existing KARMA data, there may be a risk of misclassification of fertility and infertility. For example, women reporting a history of infertility may include some fertile women who had an infertile partner.

The researchers caution that due to the cross-sectional design of the study, which assessed history of infertility and breast density at the same time, no causal links between hormonal fertility treatment, infertility and breast density could be established. Whether differences in breast density may affect potential breast cancer risk remains unknown. Given the observed, moderate association between infertility, hormonal treatments and breast density, continued monitoring of women undergoing COS is warranted, according to the researchers.

Principal investigator has been Anastasia Nyman Iliadou, Associate professor at the vid Department of Medical Epidemiology and Biostatistics. The study has been funded by the EU-FP7 Health Programme, the Swedish Research Council, and Märit and Hans Rausings initiative against breast cancer. This news article is an edited version of a press release from BioMed Central.


Association of infertility and fertility treatment with mammographic density in a large screening-based cohort of women: a cross-sectional study
Frida E. Lundberg, Anna L. V. Johansson, Kenny Rodriguez-Wallberg, Judith S. Brand, Kamila Czene, Per Hall and Anastasia N. Iliadou
Breast Cancer Research 2016 DOI: 10.1186/s13058-016-0693-5 Online 13 April 2016.