New breast cancer research has ‘immediate implications’

Androgens ­­­– the hormones that contribute to growth and reproduction in both men and women –have already been used previously to treat breast cancer, but knowledge of hormone receptors in breast tissue was rudimentary at the time and the treatment’s efficacy misunderstood.
 
According to researchers at the University of Adelaide, there has been limited progress in the development of an effective treatment strategy.
 
Androgen therapy was eventually discontinued due to virilising side effects and the advent of anti-estrogenic endocrine therapies, but University of Adelaide researchers have now confirmed it may have a role to play in the treatment of one of the most common forms of breast cancer.
 
Abnormal oestrogen activity is responsible for the majority of breast cancers, and although endocrine therapy is standard-of-care for oestrogen receptor-positive breast cancer, resistance to these drugs is the major cause of breast cancer mortality, the researchers state.
 
But now, emerging evidence about the role of androgens in breast cancer treatment, specifically on the positive effects for women with oestrogen receptor-driven metastatic disease, could provide new hope.
 
‘Previous studies had produced conflicting evidence on how best to therapeutically target the AR [androgen receptor] for treatment of breast cancer, which caused widespread confusion and hampered clinical application,’ the authors wrote.
 
‘Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent anti-tumour activity in multiple disease contexts, including resistance to standard-of-care oestrogen receptor and CDK4/6 inhibitors.
 
‘In contrast, AR inhibitors had no effect.’
 
The researchers also noted that AR agonists combined with standard-of-care agents enhanced therapeutic responses and that a gene signature of AR activity ‘positively predicted disease survival in multiple clinical oestrogen receptor-positive breast cancer cohorts’.
 
These findings provide evidence that ARs have a role in overcoming tumours in oestrogen receptor-positive breast cancer and support AR agonism as an optimal AR-directed treatment strategy, the authors concluded.
 
Lead author Associate Professor Theresa Hickey, Head of the Breast Cancer Group, said that the need for alternative treatment strategies has renewed interest in androgen therapy for breast cancer.
 
‘This work has immediate implications for women with metastatic oestrogen receptor-positive breast cancer, including those resistant to current forms of endocrine therapy,’ she said.
 
Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories, said the research presents ‘compelling new experimental evidence’ that AR-stimulating drugs can be more effective than existing or new standard-of-care treatments.
 
‘And [new standard-of-care treatments] can be combined to enhance growth inhibition,’ he said.
 
‘Moreover, currently available selective AR-activating agents lack the undesirable side effects of natural androgens, and can confer benefits in women including promotion of bone, muscle and mental health.’
 
The authors hope the new insights will clarify the ‘widespread confusion’ over the role of the AR in oestrogen receptor-driven breast cancer, given the efficacy of the treatment strategy at multiple stages of disease in the study.
 
The findings, anticipated to be translated into clinical trials as a new class of endocrine therapy, also present an application beyond the treatment of breast cancer – including breast cancer prevention and treatment of other disorders also driven by oestrogen.
 
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