High levels of anti-Müllerian hormone increase breast cancer risk among premenopausal women
A high level of anti-Müllerian hormone appeared associated with increased risk for breast cancer among a large cohort of premenopausal women, according to study results published in International Journal of Cancer.
“The link we found between the anti-Müllerian hormone and breast cancer risk is interesting because few blood markers of breast cancer risk have been identified in premenopausal women,” Anne Zeleniuch-Jacquotte, MD, professor in the department of population health and environmental medicine at NYU School of Medicine, said in a press release.
Investigators analyzed blood samples from 2,835 premenopausal women from 10 prospective cohorts with invasive breast cancer (80%) or in situ breast cancer (20%). Researchers also evaluated samples from 3,122 age-matched controls.
Zeleniuch-Jacquotte and colleagues used a high sensitivity enzyme-linked immunoabsorbent assay to measure levels of anti-Müllerian hormone (AMH) — a biomarker in the ovarian reserve — and they applied conditional logistic regression to the aggregated dataset.
An analysis adjusted for other breast cancer risk factors showed a statistically significant trend for elevated breast cancer risk with greater AMH concentration (P < .0001 for trend).
Researchers calculated an OR of 1.6 (95% CI, 1.31-1.94) for women in the top quartile of AMH concentration vs. those in the bottom quartile. This trend persisted among both premenopausal women (OR = 1.35; 95% CI, 1.05-1.73) and postmenopausal women (OR =1.61; 95% CI, 1.03-2.53).
“Our study found a moderate risk increase, and we hope that additional markers can be found, which — in combination with the anti-Müllerian hormone — could substantially improve individual prediction for breast cancer risk,” Zeleniuch-Jacquotte said in the release.
HemOnc Today spoke with Zeleniuch-Jacquotte about the study, the importance of her team’s findings, and other research underway in this area.
Question: Can you explain the study rationale?
Answer : American Cancer Society recommends annual mammography screening starting at age 45 years. The U.S. Preventive Services Task Force recommends biennial screening for women aged 50 to 74 years, though that recommendation stipulates that women may decide to start earlier based on their “values regarding specific benefits and harms.” We wanted to improve risk prediction models so women could factor in their individual risk for breast cancer when deciding at what age to start mammography screening. . Identifying markers of risk is the first step in improving risk-prediction models. Providing young women with an accurate estimate of their risk for breast cancer also could help them to decide whether to take tamoxifen for breast cancer prevention when relatively young.
Q: What makes this study unique ?
A: Our study was the first consortium study of a large number of women to assess the magnitude of risk associated with AMH level. Each cohort included women with different characteristics who lived across the United States, United Kingdom, Italy and Sweden, providing confidence in the generalizability of the findings. There had not been many studies like this conducted, and the magnitude of the increase in risk observed in these studies varied. Larger studies provide more precise estimates of risk.
Q: How might your key findings be incorporated into risk-prediction models to better identify women at elevated risk for breast cancer?
A: The Gail model — the risk-prediction model most commonly used for women who are not known to be at increased risk for breast cancer due to family history or genetic mutation — is available online under the name Breast Cancer Risk Assessment Tool. The model predicts risk for breast cancer based on age, race/ethnicity, age at menarche and first full-term pregnancy, family history of breast cancer, and history of benign breast disease. This model provides fairly good estimates of the number of women who will develop breast cancer within groups defined by age and other characteristics, but it is not good at predicting which women will develop breast cancer and which women will not. Including markers strongly associated with breast cancer risk in this model could improve individual risk prediction.
Q: What additional research is planned?
A: We are looking at the effect of including AMH and testosterone — another hormone associated with increased risk for breast cancer when measured before menopause — in the Gail model on risk-prediction accuracy. These results are not yet published. However, because the increased risk associated with AMH and testosterone is of moderate magnitude, we can already say that additional markers will be needed to improve the accuracy of the Gail model to a level that would justify measuring these hormones for breast cancer risk prediction. It is, therefore, important to continue to look for markers of breast cancer risk.
Q: Is there anything else that you would like to mention?
A: International collaborations like this 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. – by Jennifer Southall
Reference:
Ge W, et al. Int J Cancer. 2018;doi:10.1002/ijc.31249.
For more information:
Anne Zeleniuch-Jacquotte, MD, can be reached at NYU Langone Academic Office, 650 First Ave., Fifth Floor, New York, NY 10016; email: anne.jacquotte@nyulangone.org.
Disclosure: Zeleniuch-Jacquotte reports no relevant financial disclosures.
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