Having high levels of anti-Müllerian hormone (AMH)—a hormone that indicates the size of a woman’s ovarian reserve—before menopause is associated with an increased risk of breast cancer, research suggests.

 

In a major study, leading scientists from the NYU School of Medicine analyzed blood samples from participants of ten cohort studies—including the Breast Cancer Now Generations Study at The Institute of Cancer Research, London—to examine the association of AMH levels with breast cancer risk.

The team examined blood samples from 5,957 premenopausal women from across the USA, the UK, Sweden, and Italy, and found that those in the quartile with the highest levels of AMH in their blood were 60% more likely to develop breast cancer—both before and after menopause—when compared to those in the lowest quartile.

AMH is produced in the ovaries, and blood levels of the hormone are commonly incorporated into fertility tests. High levels of the hormone indicate a larger ovarian reserve—the capacity of the ovaries to produce viable egg cells.

AMH is a marker of time to menopause, with levels peaking between the ages of 20-25, before declining and becoming undetectable after menopause.

Those with higher AMH levels for their age tend to reach menopause later in life, which is itself known to be a risk factor for breast cancer—but the study found that AMH levels predict breast cancer risk even for cases of breast cancer that occur before menopause.

Increase in breast cancer risk

The analysis, published in the International Journal of Cancer, was led by Anne Zeleniuch-Jacquotte, Professor in the Departments of Population Health and Environmental Medicine at NYU School of Medicine, in collaboration with colleagues at The Institute of Cancer Research (ICR).

The team examined AMH levels in participants’ blood samples that had been collected prospectively, comparing those in the highest quartile (top 25%) for AMH levels with those in the lowest quartile (bottom 25%).

In the analysis of 2,835 participants with breast cancer and 3,122 controls of similar ages, higher levels of AMH were found to be significantly associated with an increase in breast cancer risk, with the trend being seen across the entire range of AMH levels.

Results were adjusted for potential confounding risk factors for breast cancer, such as BMI, how many children each woman had had, a family history of breast cancer, and the age at which each woman started her periods (menarche).

Looking at whether AMH levels were linked to risk of developing breast cancer of a certain subtype, the team found that those with the highest levels of AMH were 96% more likely to develop breast cancer that is susceptible to being driven by both estrogen and progesterone (ER+PR+ breast cancer) than those with the lowest levels of AMH.

'International collaborations are critical'

The team is now examining whether incorporating AMH levels into current risk prediction models could lead to improved prediction of breast cancer risk in premenopausal women.

It is hoped that being able to incorporate these hormone levels could help provide a more accurate indicator of risk for younger women, in particular to identify those at a higher risk of developing hormone-positive forms of breast cancer—providing women with more information on whether risk-reducing measures would be appropriate for them.

Professor Zeleniuch-Jacquotte said:

“The link we found between anti-Müllerian hormone and breast cancer risk is interesting because few markers of risk in the blood have been identified for premenopausal women. Our study found a moderate risk increase, and we hope additional markers can now be found to help substantially improve individual risk prediction.”

“International collaborations like this one are critical to finding blood markers of breast cancer in younger women because individual studies often enroll too few young women to provide reliable results.”

'Strongest evidence yet' of breast cancer link

Study coauthor Anthony Swerdlow, Professor of Epidemiology at The Institute of Cancer Research, London, who leads the Breast Cancer Now Generations Study, said:

“Our collaborative study gives the strongest evidence yet that anti-Müllerian hormone levels are linked with women’s risk of breast cancer. In future, anti-Müllerian hormone could be factored into new ways of predicting individual women’s risk of developing the disease.”

“The causes of breast cancer are highly complex and not yet fully understood. Pooling together large datasets is key to understanding how the many different causes interact and affect breast cancer risk.”

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which helped fund the research, said:

“The discovery that high levels of anti-Müllerian hormone in the blood could indicate women at an increased risk of breast cancer is really promising.”

“We now need to understand whether adding this blood test to current prediction tools could help give women a clearer picture of their risk, and identify those who could benefit from more frequent screening or preventive measures, such as tamoxifen.”

'Vital to build an understanding'

“Breast cancer risk is affected by a combination of our genes, lifestyle choices, and events throughout life. With many contributing factors, such as pregnancy and menopause, relating to female sex hormones, it is vital that we continue to build our understanding of how these hormones affect women’s risk.”

“Whilst there are some things you can’t change, there are steps all women can take to lower their breast cancer risk, such as maintaining a healthy weight, reducing your alcohol intake, and keeping physically active.”

The Breast Cancer Now Generations Study is a landmark prospective study of the causes of breast cancer that is following over 113,000 UK women for 40 years.

With more women being diagnosed with breast cancer than ever before, the Study—which is based at The Institute of Cancer Research—continues to investigate the genetic, lifestyle, and environmental factors that may change a woman’s risk of developing breast cancer.

The Study has already led to a number of significant discoveries into the interlinked causes of breast cancer, including clarifying that women taking combined HRT are 2.7 times more likely to develop breast cancer than non-users, and that smoking is particularly associated with an increased risk of breast cancer among those who began smoking during adolescence.