Vaishnavi Kardale, Bioinformatics Centre, Savitribai Phule Pune University
Breast cancer is the second most common type of cancer in women after skin cancer. It is caused by uncontrollable growth in breast cells which then accumulate, resulting in the formation of a lump or mass. Breast cancer can be caused by mutations in genes. Some of the most common genes that can lead to breast cancer on mutation are (Breast Cancer gene1) BRCA1 and (Breast Cancer gene2) BRCA2. Hormonal, lifestyle, and environmental factors may increase the risk of breast cancer in some people.
Steroid hormones and breast cancer:
Steroid hormones have a strong influence on the development of breast cancer. The breast cancer cells have a receptor attached to their surface. These receptors can attach to hormones like estrogen and progesterone which helps them to grow. If breast cancer cells have a receptor for estrogen they are called estrogen-positive (ER-positive), if they have progesterone then they are called progesterone-positive (PR-positive), if they have both the receptors they are called hormone receptor-positive, and if they have none they are called hormone receptor-negative. Knowing what type of receptor is present on the cancer cells helps the physician in planning the subsequent treatment for the patient. Estrogen and progesterone hormones bind to their respective receptors and fuel the growth of cancerous cells. Hormone therapy, also known as endocrine therapy, stops these hormones from attaching to the receptor. These therapies cannot be used for women that have hormone negative breast cells. Endocrine therapies are used as an adjuvant after surgical removal of the tumor to prevent a relapse. In women who develop breast cancer after menopause a special treatment called Aromatase Inhibitor (AI) medication is used. This cannot be used for other women.
What did the study find?
Steroids play an essential role not just in growth and reproduction but also in circadian rhythm, xenobiotic response, cancer, and basal and lipid metabolism. Due to their impact on so many different processes, there is now a renewed focus on alternate steroids that may facilitate breast cancer progression. A high level of androgens binds to the receptor-positive and receptor-negative breast cancer cells. They are shown to have a pro-tumorigenic response. The study shows that androgen could elicit the response despite the absence of androgen-specific receptors. This suggests that estrogen and progesterone are not the only steroid drivers of breast cancer. Androgen receptors (AR) are also found on some breast cells. It is well known that bioavailable androgens sometimes drive resistance to endocrine/hormonal therapy. A novel finding was that the androgenic steroid environment resulted due to Aromatase Inhibitor (AI) therapy-induced AR-mediated gene changes that resulted in a poor response to endocrine therapies that is commonly known as endocrine resistance. The Androgenic Receptor (AR) blocks the tumorigenic potential of the Estrogen Receptor (ER). This finding can be associated with favorable progression-free survival in the total population.
So, what next?
Most studies put a focus on the presence or absence of receptors on the cancer cells. However, little attention is given to the presence of ligands. The effect of age-related changes in endocrine hormones is also fairly overlooked. More studies need to be performed to analyze the role that these can have on breast cancer progression and its possible role on endocrine resistance. With advanced biomarker assessment platforms, this has become a burgeoning area of research. While determining the treatment; the role of steroid receptors, their ligands, and the signal transduction pathway should be factored in. As the level of steroid hormones is shown to affect breast tumor progression the treatment for postmenopausal and premenopausal should be formulated having quantified their levels. With a better understanding of the role of steroids in cancer progression, better treatments can be offered to breast cancer patients.
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Reference:
- Bleach, R., Madden, S. F., Hawley, J., Charmsaz, S., Selli, C., Sheehan, K. M., Young, L. S., Sims, A. H., Souček, P., Hill, A. D., & McIlroy, M. (2021). Steroid ligands, the forgotten triggers of nuclear receptor action; implications for acquired resistance to endocrine therapy. Clinical Cancer Research, 27(14), 3980–3989. https://doi.org/10.1158/1078-0432.CCR-20-4135
Author info:
Vaishnavi Kardale is a master’s student at the Bioinformatics Centre, Savitribai Phule University. She is interested in protein folding mechanisms and wants to study them further.
Some of her previous publications are:
- https://bioxone.in/news/worldnews/the-gene-responsible-for-eye-lens-formation-revealed/
- https://bioxone.in/news/worldnews/comeback-of-tuberculosis-but-its-drug-resistant-now/
- https://bioxone.in/news/worldnews/a-drug-to-reduce-covid-infection-by-99/
- https://bioxone.in/news/worldnews/artificial-intelligence-ai-for-efficient-covid-testing/
- https://bioxone.in/news/worldnews/deephbv-a-machine-learning-tool-to-aid-in-hepatitis-b-integration-site-detection/
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