Anti‐Mullerian hormone and breast cancer risk—is the correlation possibly associated with the PCOS?

Abstract

Dear Editor, Ge et al. 1 have recently found an association between high circulating Anti Mullerian Hormone (AMH) levels and breast cancer. The authors tested this correlation by conducting nested case-control studies within ten different cohorts, and found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer. 1 The authors cite previous laboratory experiments whereby AMH stimulated apoptosis and reduced breast tumor growth, suggesting a protective role. [2][3][4] This apparent controversy seems intriguing, and the authors suggest that additional mechanisms may be at play. 1 The polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy in premenopausal women, ranging from 5% to 10% and is associated with oligo-amenorrhea, infertility, fewer deliveries, and shorter lactation periods compared to a control population. 5 Furthermore, the PCOS is associated with significantly higher AMH levels than normal ovulatory women. 6,7 In addition, a possible association between PCOS, high AMH, and cardiovascular risk has been recently questioned. 7 Even more intriguing, an associated between PCOS and breast cancer has been suggested. 8 PCOS may raise a woman's risk of developing uterine cancer 10-folds and breast cancer almost two folds. 8 The adjusted hazard ratio (HR) of uterine cancer and breast cancer in subjects with PCOS were higher than that of the controls, (HR: 8.42 [95% confidence interval: 1.62-43.89] and HR: 1.99 [95% confidence interval: 1.05-3.77], respectively). 8 Others have also found 2.74-increased odd ratios for breast cancer in premenopausal PCOS subjects (95% CI 1.13-6.63).

Anti-Müllerian Hormone Type II Receptor Expression in Endometrial Cancer Tissue

“…Conflicting results may indicate the involvement of additional mechanisms. It cannot be excluded that the association of high AMH levels with breast cancer may be due to a higher prevalence of PCOS, and not directly of high AMH [ 36 ]. This additionally underlines the necessity of AMH and AMHRII investigation in aspects of various patient characteristics, including comorbidities.…”

Estrogens and the risk of breast cancer: A narrative review of literature

“…The high levels of insulin that it causes in the blood, as well as having an intersection with a gene that is also present in breast cancer [ 131 ]. Also, it produces high levels of anti -Mullerian hormone (AMH) which could suggest PCOS is the original factor responsible for the increased breast cancer risk occurring in women with high levels of (AMH), not the increase in the hormone itself [ 131 , 132 ]. There are also some data like a population-based case-control study by Kim J, Mersereau JE, Khankari N et al, that does suggest it has a positive relationship with an increased risk of breast cancer occurrence specifically in premenopausal women [ 133 ].…”

The roles of anti-Müllerian hormone in breast cancer

“…In a large consortium study, Ge et al confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs bottom quartile of AMH ( Ge et al 2018 ). But this conclusion has been strongly disputed by Blumenfeld, who believes that the association of high AMH and breast cancer may be due to a higher prevalence of PCOS in the high AMH group and not due to high AMH, per se ( Blumenfeld 2019 ). However, this is also a controversial topic, because most of the literature has shown no significant association between PCOS and breast cancer risk ( Carvalho et al 2019 , Meczekalski et al 2020 ), and only a few studies have shown that PCOS may be associated with ER+ breast cancer ( Wu et al 2020 ).…”