Breast Density Higher in Infertile Women

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The medicines used to treat women’s infertility problems affect hormone levels. Hormones can play an important role in how breast cancer develops and grows. Still, several studies have found that fertility treatments don’t appear to increase breast cancer risk based on the type of fertility treatments they received.

Looking at the issue from another angle, a Swedish study has found that women with a history of infertility had denser breasts than women who didn’t have fertility problems, and infertile women who had a specific type of fertility treatment, controlled ovarian stimulation, had denser breasts than women who hadn’t received the treatment.

The study was published in the April 13, 2016 issue of the journal Breast Cancer Research. Read “Association of infertility and fertility treatment with mammographic density in a large screening-based cohort of women: a cross-sectional study.”

Dense breasts have less fatty tissue and more non-fatty tissue compared to breasts that aren't dense. Dense breasts have more gland tissue that makes and drains milk and supportive tissue (also called stroma) that surrounds the gland. One way to measure breast density is the thickness of tissue on a mammogram.

The Breast Imaging Reporting and Database Systems, or BI-RADS, which reports the findings of mammograms, also includes an assessment of breast density. BI-RADS classifies breast density into four groups:

  • Mostly fatty: The breasts are made up of mostly fat and contain little fibrous and glandular tissue.
  • Scattered density: The breasts have quite a bit of fat, but there are a few areas of fibrous and glandular tissue.
  • Consistent density: The breasts have many areas of fibrous and glandular tissue that are evenly distributed through the breasts.
  • Extremely dense: The breasts have a lot of fibrous and glandular tissue.

Still, no one method of measuring breast density has been agreed upon by doctors. Breast density is not based on how your breasts feel during your self-exam or your doctor's physical exam.

Research has shown that dense breasts:

  • can be 6 times more likely to develop cancer
  • can make it harder for mammograms to detect breast cancer; breast cancers (which look white like breast gland tissue) are easier to see on a mammogram when they're surrounded by fatty tissue (which looks dark)

To do the study, the researchers looked at information from 43,313 women who were part of the KArolinska MAmmography project, a study looking at predicting the risk of breast cancer.

The women were ages 44 to 69 and had a full-field digital mammogram when the study started. The women had regular screening mammograms every 18 to 24 months during the study. None of the women had a history of breast cancer or breast surgery. All the women filled out a web-based questionnaire that asked about:

  • age
  • education
  • height and weight
  • reproductive health/history of infertility
  • lifestyle factors, including smoking and alcohol use
  • medicines taken
  • other diseases or conditions
  • family history of breast cancer

Women who had ever tried to become pregnant for 1 year or more without success were classified as infertile (8,963 women). The researchers then noted which type, if any, of fertility treatments the women received:

  • hormonal treatment to stimulate ovulation
  • artificial insemination
  • in vitro fertilization (IVF): eggs extracted from the uterus after hormonal egg stimulation are fertilized in a test tube, grow briefly into tiny embryos, and then are frozen before being implanted back in the uterus
  • intracytoplasmic sperm injection (ICSI): ICSI is slightly different from IVF in that a single sperm is selected to be injected directly into an egg, instead of fertilization taking place in a test tube or petri dish
  • IVF with a donor egg
  • surgery
  • other

The researchers divided the women into three groups based on the type of fertility treatment they had had:

  • controlled ovarian stimulation (a high dose of a gonadotropin, a family of hormones) for IVF or ICSI (1,576 women)
  • hormonal treatment with Clomid (chemical name: clomiphene citrate) or a low dose of a gonadotropin for egg stimulation that wasn’t for IVF or ICSI (1,429 women)
  • no hormonal treatment (5,948 women)

The researchers first compared breast density levels between fertile and infertile women. Women with a history of infertility had 1.53 cm3 (0.09 cubic inches) higher volume of dense breast tissue than women who didn’t have a history of infertility.

Then the researchers compared breast density levels between infertile women who had controlled ovarian stimulation and infertile women who had not received hormonal treatment. Women who had been treated with controlled ovarian stimulation had 3.22 cm3 (0.2 cubic inches) higher volume of dense breast tissue than women who didn’t have hormonal treatment.

There was no difference in the volume of dense breast tissue between infertile women who received hormonal treatment that wasn’t controlled ovarian stimulation and infertile women who didn’t receive any hormonal treatment.

"The results from our study indicate that infertile women, especially those who undergo controlled ovarian stimulation, might represent a group with an increased breast cancer risk," said Dr. Frida Lundberg, of the Department of Medical Epidemiology and Biostatistics at the Karolinska Instituet and lead author of the study. "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."

While the results seem to suggest that controlled ovarian stimulation may be associated with a higher risk of breast cancer, other experts didn’t think the connection was strong enough.

"We've known for a long time that breast density is a risk factor for breast cancer, but none of the risk-assessment models we have can currently take breast density into account," said Julie Nangia, M.D., of the Baylor College of Medicine, in an interview.

"Studies that have looked at infertility treatments and whether short courses of hormone treatment increase the risk for breast cancer have really not been conclusive and have shown mixed results to date," she continued. "Even in this study, if you look at some of the finer points, I wonder whether some of what they are seeing is age related and associated with never having children.

"At this point, I wouldn't tell a woman that having these [fertility] treatments would put you at increased risk for breast cancer, because we just don't know," Dr. Nangia added.

If you’re considering fertility treatments or have used them in the past, this study emphasizes the importance of regular monitoring and breast cancer screening for you. It’s not clear if there is any association between fertility treatments and increased breast cancer risk. Still, there is no harm in being vigilant, especially if you’ve been told that you have dense breasts or have a family history of breast cancer.

If you’re having fertility issues, you may want to visit the RESOLVE website. RESOLVE is an organization that provides education and support to people with fertility problems and has local chapters throughout the United States. For more information, visit www.resolve.org.



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