In normal breast development, estrogen stimulates and androgen inhibits growth at puberty and throughout adult life.
Abnormal estrogen activity is responsible for the majority of breast cancers, but the role of androgen activity in this disease has been controversial.
The new research published in the journal Nature Medicine showed that androgens have potential for treatment of estrogen receptor positive breast cancer.
A cancer is called estrogen receptor positive if it has receptors for estrogen, according to Breastcancer.org.
Using cell-line and patient-derived models, the global team, including researchers at the University of Adelaide and the Garvan Institute of Medical Research in Australia, demonstrated 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.
In contrast, androgen receptor inhibitors had no effect.
“This work has immediate implications for women with metastatic estrogen receptor positive breast cancer, including those resistant to current forms of endocrine therapy,” said lead researcher Theresa Hickey, Associate Professor at the University of Adelaide.
“We provide compelling new experimental evidence that androgen receptor stimulating drugs can be more effective than existing (e.g. Tamoxifen) or new (e.g. Palbociclib) standard-of-care treatments and, in the case of the latter, can be combined to enhance growth inhibition,” said Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide.
Androgens were historically used to treat breast cancer, but knowledge of hormone receptors in breast tissue was rudimentary at the time and the treatment’s efficacy misunderstood.
Androgen therapy was discontinued due to virilising side effects and the advent of anti-estrogenic endocrine therapies.
While endocrine therapy is standard-of-care for estrogen receptor positive breast cancer, resistance to these drugs is the major cause of breast cancer mortality.
“The new insights from this study should clarify the widespread confusion over the role of the androgen receptor in estrogen receptor driven breast cancer,” said Elgene Lim, a breast oncologist and Head of the Connie Johnson Breast Cancer Research Lab at the Garvan Institute.
“Given the efficacy of this treatment strategy at multiple stages of disease in our study, we hope to translate these findings into clinical trials as a new class of endocrine therapy for breast cancer.”
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