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Androgen therapy proposed as alternative treatment for breast cancer: How it is different from endocrine therapy?

Androgen therapy proposed as alternative treatment for breast cancer: How it is different from endocrine therapy?

An international team of researchers has suggested that androgen therapy can benefit women with metastatic estrogen receptor positive breast cancer, including those resistant to current forms of endocrine therapy.

Written by Longjam Dineshwori |Updated : January 19, 2021 4:21 PM IST

Androgens are a group of hormones that are known to primarily influence the growth and development of the male reproductive system and give men their 'male' characteristics. While androgens are commonly called male hormones, they are also found at lower levels in women. The principle androgens are testosterone and androstenedione. An international research team has suggested androgen therapy as a potential treatment for estrogen receptor positive breast cancer.

Women have two main sex hormones - estrogen and progesterone. Estrogen is responsible for developing and maintaining female reproductive system and physical features, such as breasts and pubic hair. Men, too, have estrogen, but in smaller amounts. Abnormal estrogen activity is linked to majority of breast cancers. While abundant clinical evidence suggests that androgens normally inhibit breast growth, the hormone's role in breast cancer has been a disputed issue.

The international team, which includes researchers from the University of Adelaide and the Garvan Institute of Medical Research, has found a positive role of androgens in treatment for estrogen receptor-driven metastatic breast cancer. The results of their study appeared in a paper published in Nature Medicine.

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Breast cancer treatment: Androgen therapy vs endocrine therapy

Hormone therapy is recommended for women with hormone receptor positive breast cancer. Breast cancer cells have receptors (proteins) that attach to either estrogen (ER) or progesterone (PR) hormone, which helps them grow. Breast cancers that have receptors for estrogen are called estrogen receptor-positive (or ER-positive). About 80% of all breast cancers are estimated to be ER-positive. Endocrine therapy used for treatment of these type of breast cancers uses drugs that lower estrogen levels or block estrogen receptors.

While endocrine therapy is considered standard-of-care for estrogen receptor positive breast cancer, resistance to these drugs are the major cause of breast cancer mortality, noted the researchers of the new study.

They said that the need for alternative treatment strategies has renewed interest in androgen therapy for breast cancer. Androgens were earlier used to treat breast cancer, but it was discontinued due to virilizing side effects and the advent of anti-estrogenic endocrine therapies.

In cell-line and patient-derived models, the team found that androgen receptor activation by natural androgen or a new androgenic drug had potent anti-tumour activity in all estrogen receptor positive breast cancers, even those resistant to current standard-of-care treatments. However, androgen receptor inhibitors had no effect.

Good news for women with metastatic estrogen receptor positive breast cancer

The finding has immediate implications for women with metastatic estrogen receptor positive breast cancer, including those resistant to current forms of endocrine therapy, said Professor Theresa Hickey, who led the study.

Another team member Professor Tilley added their study provides compelling evidence that androgen receptor stimulating drugs can be more effective than existing (e.g. Tamoxifen) or new (e.g. Palbociclib) standard-of-care treatments.

According to the researchers, the currently available selective androgen receptor activating agents lack the undesirable side effects of natural androgens. Moreover, these agents can promote bone, muscle and mental health in women as well.

This alternative treatment strategy was found to be effective at multiple stages of breast cancer in the study. Now, the researchers are hoping to translate these findings into clinical trials as a new class of endocrine therapy for breast cancer. They believe that their finding has benefit beyond the treatment of breast cancer, and can help in breast cancer prevention and treatment of other disorders also driven by estrogen too.

With agency inputs