One of the major initiatives of BCRF’s Evelyn H. Lauder Founder’s Fund for Metastatic Breast Cancer, reported promising results from analyses of more than 300 primary and metastatic tumors

One of the programs that BCRF supports as part of its significant investment in metastatic breast cancer research has just published its first study—the results of which already help deepen our understanding of the molecular changes driving this disease.

The European AURORA study (also known as AURORA-EU) conducted multi-platform analyses on matched primary and metastatic tumors from the study’s first 381 enrolled patients. Their initial results, published this week in the journal Cancer Discovery, showed that metastatic tumors had significant differences in molecular subtype, genomic landscape, and immune microenvironment compared to primary tumors. In addition, the researchers noted that there are existing targeted therapies for approximately 50 percent of patients whose breast cancer metastases harbored unique molecular changes.

These findings, which could lead to the development of better treatments for patients with metastatic breast cancer, will be further validated in the full cohort of AURORA-EU patients, which now total more than 1,000.

“This study offers a unique opportunity to generate robust findings that will help us better understand the evolution of metastatic breast cancer,” said BCRF investigator Dr. Martine Piccart, the lead investigator of the study. “True to its name, AURORA will bring light to the dark landscape of advanced breast cancer.”

Metastatic breast cancer: An urgent research priority

Last year, about 685,000 people died from breast cancer worldwide. Metastatic breast cancer—when the disease spreads to other areas of the body—is the leading cause of these deaths. While metastatic breast cancer (also known as stage IV breast cancer) can be treated, the disease remains incurable. In the U.S., an estimated 168,000 women are living with metastatic breast cancer right now.

AURORA-EU was launched in 2014 by the Breast International Group, led at the time by BCRF researcher and Scientific Advisory Board member Dr. Piccart. BCRF, through the Evelyn H. Lauder Founder’s Fund for Metastatic Breast Cancer, is a primary funder of AURORA-EU, along with AURORA-US.

The AURORA programs are complimentary in their goals. AURORA-US aims to characterize the molecular underpinnings driving tumor evolution from the primary tumor in the breast to distant, life-threatening disease, while AURORA EU is focused on the evolving molecular landscape during tumor evolution with a particular emphasis on how this tumor evolution effects response to therapies.

Collectively, the AURORA programs will help the research community identify those at risk of metastasis before it occurs or much earlier, and find new, more effective therapies or improve response to existing ones.

“The AURORA-EU project is providing critical insights with near-term translation into therapeutic strategies for women with metastatic disease, a major research priority of the BCRF," said BCRF Scientific Director Dr. Judy Garber. "The insights from the AURORA-EU project will stimulate other researchers and AURORA-EU to accelerate progress against this clearly diverse and challenging diagnosis.”

Over 60 hospitals across 11 European countries are participating in the AURORA-EU study, which has enrolled 1,150 women and men with metastatic breast cancer to date. It is unique in its vast collection of matched primary and metastatic tumors (from the same patient), serially collected blood samples, and highly curated clinical data. The study investigators expect to collect approximately 30,000 blood and tumor tissue samples throughout the course of the study, which will follow patients for 10 years. With these samples and data, researchers will then be able to study changes in breast cancer tumors throughout the course of therapy and analyze what causes cancer to spread. They are currently analyzing 411 genes in both primary and metastatic tumors.

More highlights from AURORA-EU’s findings

AURORA-EU’s current report is based on the first 381 patients enrolled in the study, and it already identified unique changes in the metastatic lesion compared to the primary tumor, including:

  • Gene mutations and copy number variants (genomic changes that increase or decrease the activity of a gene) in key tumor-driving genes were found in 10 and 30 percent, respectively, of samples analyzed. If validated in the full cohort of patients, this information could inform the development of new targeted therapies.
  • Changes in molecular subtype (luminal A, Luminal B, HER2-enriched, basal-like), usually from less aggressive to more aggressive, were observed. This “subtype switching” occurred in about 37 percent of the matched samples, which, if further validated, could have significant implications for treatment decisions.
  • Loss of immune-related signature genes and changes to immune cell composition in the tumor microenvironment were observed. This finding suggests that the tumor is manipulating its environment to grow and could lead to both new immunotherapies and strategies to prevent tumor spreading.

The AURORA investigators also reported that certain patients with normally less-aggressive estrogen receptor (ER)–positive and HER2-negative breast cancer had worse outcomes if their tumor had acquired a lot of gene mutations (what’s known as high tumor mutational burden), making this a potential prognostic biomarker. Another important finding is that for 50 percent of patients whose tumors harbor molecular alterations, there are existing targeted therapies that could benefit these patients today.

AURORA is the largest international molecular screening program involving paired biopsies, blood samples, and a rich set of clinical and molecular data collected longitudinally from patients with MBC. It represents a tremendous logistical effort and a valuable resource that could support the next generation of hypotheses for new treatment strategies for this devastating disease.

“BCRF is proud to support this extraordinary multinational study and the many years of meetings between clinical investigators, who identified the need for such a focused collaboration,” said BCRF Founding Scientific Director Dr. Larry Norton. “We expect that this work and its US-based counterpart—which both continue with BCRF support—will provide essential information to allow us to solve the most important problem in breast cancer: the causes and therapeutic vulnerabilities of metastases.”

BCRF’s Chief Scientific Officer Dr. Dorraya El-Ashry added that this research represents one of the Foundation’s core principles: collaboration.

“The Evelyn H. Lauder Founder’s Fund and the AURORA projects are the best demonstration of BCRF’s international, cross-disciplinary approach that accelerates the entire field,” she said. “These projects are urgent in their focus on the biggest problem in breast cancer research: finding a cure for the nearly 700,000 people around the world who die from this disease each year.”

RELATED:

 

BCRF’s Guide to Metastatic Breast Cancer Symptoms, Treatment, and Research

About the Evelyn H. Lauder Founder's Fund for Metastatic Breast Cancer Research

BCRF’s Commitment to Metastatic Breast Cancer Research

More on AURORA-US (Video)

Dr. Martine Piccart on the BCRF Podcast

The AURORA-US Project Reports First Key Findings of Changes Between Primary Tumors and Metastases

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