A drug that reduces fracture risk in postmenopausal breast cancer patients taking aromatase inhibitors (AIs) appears also to cut their risk of relapse, a researcher said here.

In a prospective randomized placebo-controlled trial, adjuvant denosumab (Prolia), given twice a year, was associated with a 19% improvement in disease-free survival (DFS), according to  http://surgery.chirurgiewien.at/michael-gnant/dr-gnant-inperson/" rel="nofollow - Michael Gnant, MD , of the Medical University of Vienna.

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People who carry a faulty BRCA1 gene are at high risk of developing aggressive breast cancer. Currently many women with a gene mutation choose surgical removal of their breast tissue and ovaries to reduce their chance of developing breast and http://www.medicalnewstoday.com/articles/159675.php" rel="nofollow - ovarian cancer .

By pinpointing the cells that give rise to breast cancers in women who have inherited a faulty version of the BRCA1 gene, Walter and Eliza Hall Institute researchers have identified that the drug denosumab may have potential to prevent breast cancer from developing. If confirmed in clinical studies, this would provide a non-surgical option to prevent breast cancer in women with elevated genetic risk.

Using samples of breast tissue donated by women carrying a faulty BRCA1 gene, Ms Emma Nolan, Professor Jane Visvader and Professor Geoff Lindeman were able to pinpoint the cells that give rise to breast cancer. The research, which also involved researchers at the Australian familial  http://www.medicalnewstoday.com/info/cancer-oncology/" rel="nofollow - cancer  consortium kConFab and US biotechnology company Amgen was published in Nature Medicine.

Cancer precursor cells in BRCA1-mutant breast tissue had many similarities to aggressive forms of breast cancer, said Ms Nolan, who is a PhD student at the institute enrolled through The University of Melbourne's Department of Medical Biology. "These cells proliferated rapidly, and were susceptible to damage to their DNA - both factors that help them transition towards cancer," she said. "We were excited to discover that these pre-cancerous cells could be identified by a marker protein called RANK."

Professor Lindeman, who is also a medical oncologist at The Royal Melbourne Hospital, said the discovery of RANK as a marker of cancer precursors was an important breakthrough, because inhibitors of the RANK signalling pathway were already in clinical use. "An inhibitor called denosumab is already used in the clinic to treat  http://www.medicalnewstoday.com/articles/155646.php" rel="nofollow - osteoporosis  and breast cancer that has spread to the bone," he said. "We therefore investigated what effect RANK inhibition had on the cancer precursor cells in BRCA1-mutant breast tissue."

The research team showed that RANK inhibition switched off cell growth in breast tissue from women with a faulty BRCA1 gene and curtailed breast cancer development in laboratory models.

"We think this strategy could delay or prevent breast cancer in women with an inherited BRCA1 gene mutation," Professor Lindeman said. "A clinical trial has already begun to investigate this further."

"This is potentially a very important discovery for women who carry a faulty BRCA1 gene, who have few other options. Current cancer prevention strategies for these women include surgical removal of the breasts and/or ovaries, which can have serious impacts on people's lives. To progress this work, denosumab would need to be formally tested in clinical trials in this setting as it is not approved for breast cancer prevention," Professor Lindeman said.

Professor Visvader said the discovery had its basis in more than a decade of investigations of breast  http://www.medicalnewstoday.com/info/stem_cell/" rel="nofollow - stem cell  function. "By thoroughly dissecting how normal breast tissue develops, we have been able to pinpoint the precise cells that are the culprits in cancer formation," she said. "It is very exciting to think that we may be on the path to the 'holy grail' of cancer research, devising a way to prevent this type of breast cancer in women at high genetic risk."

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Inhibition of the RANK pathway significantly reduces recurrence and metastasis in breast cancer mouse models, according to the results of a recent study published in  http://cancerres.aacrjournals.org/" rel="nofollow - - Cancer Research .

The study, “ http://cancerres.aacrjournals.org/content/early/2016/07/30/0008-5472.CAN-15-2745.full-text.pdf" rel="nofollow - RANK signaling blockade reduces breast cancer recurrence by inducing tumor cell differentiation ,” shows that RANK inhibition reduces cancer stem cells (CSC) in invasive tumors, impairing the start of metastasis, and enhances sensitivity to  https://breastcancer-news.com/chemotherapy/" rel="nofollow - chemotherapy .

“Mortality in breast cancer is mainly due to survivor CSC after treatments, which are responsible for tumor recurrence and metastasis,” Dr. Eva Gonzalez-Suarez, the study’s lead author, said in a  https://www.sciencedaily.com/releases/2016/09/160913095932.htm" rel="nofollow - press release . “Previous studies of this and other research groups have shown that inhibition of RANK pathway may prevent breast cancer, but no one had proven the potential of RANK pathway inhibitors in the treatment of disease.”

In normal conditions, the RANK signaling pathway works to promote the development of the mammary gland in response to signals provided by sex hormones, such as progesterone. This usually happens in all women during their menstrual cycles and during  https://breastcancer-news.com/breast-cancer-during-pregnancy/" rel="nofollow - pregnancy , but if the RANK signaling becomes disregulated, the mammary cells start reproducing rapidly when they are not supposed to, eventually leading to breast cancer.

Expression of RANK in human cancers is linked with reduced overall survival, but the therapeutic potential of RANK inhibitors once tumors have developed remained to be addressed.

In this study, Gonzalez-Suarez and her team used a breast cancer mouse model with high RANK expression and explored whether RANKL inhibitors could be used to prevent cancer progression.

The researchers found that “this inhibition does not reduce tumor growth, but promotes differentiation, reducing the population of CSC and impairing metastasis, which improves the prognosis,” suggesting that inhibition of the RANK/RANKL pathway could be potentially used as a new therapy in breast cancer.

Importantly, RANKL inhibitors, such as Prolia (denosumab), are already approved in the clinic and are indicated for the treatment of bone related diseases, osteoporosis, and bone metastasis, and thus may quickly become available for patients with advanced breast cancer.

“As these preclinical experiments suggest, and given that the RANKL / RANK pathway plays an important role in the development of primary breast cancer, inhibitors could serve as a potential target for the prevention and nonsurgical treatment of breast cancer,” Gonzalez-Suarez said.

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