The roles of anti-Müllerian hormone in breast cancer

Abstract

Anti-Müllerian hormone (AMH) is produced and secreted by granulosa cells of growing follicles, and its main role is to inhibit the recruitment of primordial follicles, reduce the sensitivity of follicles to follicle-stimulating hormone (FSH), and regulate FSH-dependent preantral follicle growth. It has become an effective indicator of ovarian reserve in clinical practice. Research on AMH and its receptors in recent years has led to a better understanding of its role in breast cancer. AMH specifically binds to anti-Müllerian hormone receptor II (AMHRII) to activate downstream pathways and regulate gene transcription. Since AMHRII is expressed in breast cancer cells and triggers apoptosis, AMH/AMHRII may play an important role in the occurrence, treatment, and prognosis of breast cancer, which needs further research. The AMH level is a potent predictor of ovarian function after chemotherapy in premenopausal breast cancer patients older than 35 years, either for ovarian function injury or ovarian function recovery. Moreover, AMHRII has the potential to be a new marker for the molecular typing of breast cancer and a new target for breast cancer treatment, which may be a link in the downstream pathway after TP53 mutation.

Keywords: anti-Müllerian hormone; anti-Müllerian hormone receptor II; breast cancer; hypothalamic–pituitary–ovarian axis; ovarian function.

Figure 1

AMH/AMHRII participates in the hypothalamic–pituitary–ovarian axis. AMH secreted from granulosa cells of growing follicles can target AMHRII, which is located in the hypothalamus, pituitary, and ovary, interacts with hormones secreted from these organs, and forms a complex hormonal network. A full colour version of this figure can be found at https://doi.org/10.1530/ERC-23-0060.

Figure 2

Possible mechanisms of AMH/AMHR2 in breast cancer. The hypothesis that estrogen may inhibit the expression of AMHRII in ER+ breast cancer cells and the mechanism by which AMH targets AMHRII leads to apoptosis in breast cancer was shown in the figure. A full colour version of this figure can be found at https://doi.org/10.1530/ERC-23-0060.

Figure 3

AMHR2 gene expression is negatively correlated with breast cancer. A violin plot comparing AMHR2 expression in breast tumor samples (n = 70) and adjacent normal tissue (n = 70). *P < 0.05, **P < 0.01, and ***P < 0.001. A full colour version of this figure can be found at https://doi.org/10.1530/ERC-23-0060.

Figure 4

The level of AMHR2 gene expression in breast cancer tumors can predict the prognosis. (A–E) Overall survival according to the AMHR2 gene expression. (F–J) Relapse-free survival according to the AMHR2 gene expression. (K–O) Distant metastasis-free survival according to the AMHR2 gene expression. (A), (F), and (K) Overall breast cancer. (B), (G), and (L) Luminal A breast cancer. (C), (H), and (M) Luminal B breast cancer. (D), (I), and (N) HER2 breast cancer. (E), (J), and (O) Basal like breast cancer. *P < 0.05, **P < 0.01, and ***P < 0.001. A full colour version of this figure can be found at https://doi.org/10.1530/ERC-23-0060.

Figure 5

The mechanism by which AMH protects ovarian function during CTX. AMH can inhibit the activation of primordial follicles by preventing CTX-induced phosphorylation of FoxO3A, which can activate the PI3K/AKT/mTOR pathway and suppress autophagy to consume primordial follicles. Meanwhile, AMH can directly trigger autophagy to inhibit the activation and recruitment of primordial follicles and prevent POI. A full colour version of this figure can be found at https://doi.org/10.1530/ERC-23-0060.

Figure 6

The AMHR2 gene expression in breast cancer patients with the different therapeutic responses for three kinds of treatments is different. (A) endocrine therapy; (B) anti-HER2 therapy; (C) chemotherapy. *P < 0.05, **P < 0.01, and ***P < 0.001. A full colour version of this figure can be found at https://doi.org/10.1530/ERC-23-0060.

Figure 7

Patients suffering from breast cancer with different TP53 mutation statuses have different expressions of the AMHRII gene. Patients with a mutant TP53 gene had lower expression of the AMHRII gene than patients with a wildtype TP53 gene (P < 0.001).