Abstract

BackgroundOvarian stimulation drugs, in particular hormonal agents used for controlled ovarian stimulation (COS) required to perform in vitro fertilization, increase estrogen and progesterone levels and have therefore been suspected to influence breast cancer risk. This study aims to investigate whether infertility and hormonal fertility treatment influences mammographic density, a strong hormone-responsive risk factor for breast cancer.MethodsCross-sectional study including 43,313 women recruited to the Karolinska Mammography Project between 2010 and 2013. Among women who reported having had infertility, 1576 had gone through COS, 1429 had had hormonal stimulation without COS and 5958 had not received any hormonal fertility treatment. Percent and absolute mammographic densities were obtained using the volumetric method Volparaā„¢. Associations with mammographic density were assessed using multivariable generalized linear models, estimating mean differences (MD) with 95 % confidence intervals (CI).ResultsAfter multivariable adjustment, women with a history of infertility had 1.53 cm3 higher absolute dense volume compared to non-infertile women (95 % CI: 0.70 to 2.35). Among infertile women, only those who had gone through COS treatment had a higher absolute dense volume than those who had not received any hormone treatment (adjusted MD 3.22, 95 % CI: 1.10 to 5.33). No clear associations were observed between infertility, fertility treatment and percent volumetric density.ConclusionsOverall, women reporting infertility had more dense tissue in the breast. The higher absolute dense volume in women treated with COS may indicate a treatment effect, although part of the association might also be due to the underlying infertility. Continued monitoring of cancer risk in infertile women, especially those who undergo COS, is warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0693-5) contains supplementary material, which is available to authorized users.

Highlights

  • Ovarian stimulation drugs, in particular hormonal agents used for controlled ovarian stimulation (COS) required to perform in vitro fertilization, increase estrogen and progesterone levels and have been suspected to influence breast cancer risk

  • We aim to investigate the associations between infertility, hormonal fertility treatments and mammographic density in a large screening-based cohort of Swedish women

  • Infertile women with no hormone treatment, as well as those who had hormonal treatment without COS, had higher absolute dense and non-dense volume compared to non-infertile women, while percent dense volume was similar in these three groups

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Summary

Introduction

In particular hormonal agents used for controlled ovarian stimulation (COS) required to perform in vitro fertilization, increase estrogen and progesterone levels and have been suspected to influence breast cancer risk. This study aims to investigate whether infertility and hormonal fertility treatment influences mammographic density, a strong hormone-responsive risk factor for breast cancer. For treatments involving in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), high doses of gonadotropins are required to stimulate multiple follicle recruitment (controlled ovarian stimulation, COS). Since all these treatments increase estrogen and progesterone levels, they have been suspected to influence breast cancer risk [3, 4]. Many studies suffer from methodological limitations, including limited control for confounding factors, lack of an appropriate reference group, and short follow-up with small numbers of breast cancer cases among women using hormonal fertility treatment [5]

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