New discovery in breast cancer treatment

January 18, 2021

Researchers at the University of Adelaide have found new evidence about the positive role of androgens in breast cancer treatment with immediate implications for women with estrogen receptor-driven metastatic disease.

Published today in Nature Medicine, the international study conducted in collaboration with the Garvan Institute of Medical Research, looked at the role of androgens - commonly thought of as male sex hormones but also found at lower levels in women - as a potential treatment for estrogen receptor positive breast cancer.

Watch a video explainer about the new study at - https://youtu.be/NYalzv4C35U

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.

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 are the major cause of breast cancer mortality.

Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories, and Associate Professor Theresa Hickey, Head of the Breast Cancer Group, who led the study say the need for alternative treatment strategies has renewed interest in androgen therapy for breast cancer.

However, previous studies had produced conflicting evidence on how best to therapeutically target the androgen receptor for treatment of breast cancer, which caused widespread confusion and hampered clinical application.

Using cell-line and patient-derived models, a global team, including researchers at the University of Adelaide and the Garvan Institute, 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 Associate Professor Theresa Hickey.

Professor Tilley added: "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.

Moreover, currently available selective androgen receptor activating agents lack the undesirable side effects of natural androgens, and can confer benefits in women including promotion of bone, muscle and mental health.

Associate Professor Elgene Lim, a breast oncologist and Head of the Connie Johnson Breast Cancer Research Lab at the Garvan Institute, said: "The new insights from this study should clarify the widespread confusion over the role of the androgen receptor in estrogen receptor driven breast cancer. 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."

Dr Stephen Birrell, a breast cancer specialist and pioneer in androgens and women's health who was part of the Adelaide based team, pointed out that this seminal finding has application beyond the treatment of breast cancer, including breast cancer prevention and treatment of other disorders also driven by estrogen.

Chloe Marshall, 33, has a breast cancer recurrence while pregnant with her second child. She said that endocrine therapy has terrible side effects and there was an urgent need for better options to prevent and treat breast cancer recurrence.

"I was diagnosed with a hormone positive breast cancer in July 2017 and subsequently found out I carried the BRACA gene,'' she said.

"I underwent a double mastectomy and neo adjuvant chemotherapy followed by two years of hormone suppressive treatment. The hormone suppressive treatment that I experienced was one of the hardest parts of having cancer. The impact it has on your mind/life/body is incredibly challenging.

"Now, three years later, I find myself with a recurrent cancer while 25 weeks pregnant. The thought of having hormone suppressive treatment for a further five to ten years is overwhelming.

"I think this study will help patients like myself have hope that there is another answer to life after the cancer diagnosis."
-end-
An international Phase 3 registration clinical trial (sponsored by VERU, Inc) evaluating Enobosarm, an androgen receptor activating agent, in patients with androgen receptor and estrogen receptor positive metastatic breast cancer who failed endocrine therapy and a CDK 4/6 inhibitor (e.g. palbociclib), will commence in the second quarter of 2021.

This work was funded by grants from the National Health and Medical Research Council of Australia, the National Breast Cancer Foundation, Cancer Australia, Movember, The Hospital Research Foundation and the US Department of Defense Breast Cancer Research Program.

University of Adelaide

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.