San Antonio, TX, Dec 12—Today, investigators of BCRF’s AURORA-US project announced the discovery of key molecular changes between primary tumors and metastases, particularly between Luminal-type tumors and Basal-like tumors. The results, presented at the San Antonio Breast Cancer Symposium by lead investigators Drs. Tari King and Charles Perou, highlight promising new avenues for research.
The AURORA-US and AURORA-EU projects are the centerpiece of the Breast Cancer Research Foundation’s Evelyn H. Lauder Founder’s Fund and were established in conjunction with the Translational Breast Cancer Consortium (TBCRC). The AURORA-US project was established to conduct precise molecular analyses of primary and metastatic breast cancer samples to better understand the evolution of metastasis and the mechanisms of drug resistance that allow tumors to grow and spread. Investigators collected primary breast cancer-metastasis pairs for multi-platform genomic profiling in order to identify the molecular drivers of metastatic disease.
In this first report of the retrospective phase of the study, archived tissue samples from the primary tumor and at least one distant metastasis were collected from 10 TBCRC institutions. In total, samples from 55 patients, including 105 distinct metastatic lesions, were subject to multiple DNA and gene expression genomic analyses — the most comprehensive analysis to date of metastatic lesions.
When comparing features of the primary tumors and patient-matched metastatic lesions, changes in both gene expression and gene regulation appeared to differ between luminal-type tumors, the breast cancer molecular subtype that is typically estrogen-dependent, and basal-like tumors. Specifically, luminal-type primary tumors and their metastatic pairs frequently differed in the expression of genes that define the classic breast cancer molecular subtypes, resulting in a change in subtype classification in approximately 30% of cases. On the other hand, basal-like primary tumors tended to retain their basal-like characteristics in the matched metastatic lesions.
Other notable differences in gene expression between primary tumors and metastatic lesions suggest a prominent role for the tumor microenvironment in metastasis. Immune-related gene expression was higher in basal-like primary tumors and was down-regulated in the metastatic lesions; at the same time, immune-related gene expression was lower at baseline in luminal-type tumors and did not change with progression to metastatic disease. In contrast, expression levels of genes related to the stromal content of tumors such as normal fibroblasts were higher in luminal-type primary tumors and significantly decreased in the paired metastases.
“These observations suggest that depending on the breast cancer subtype, there are varying changes happening in tumor progression, and/or in response to treatment,” Dr. King said, “and this highlights the need to biopsy and study metastatic lesions as opposed to relying on information from the primary tumor.”
While findings from this retrospective phase are the first step towards unraveling the mystery of metastasis, it underscores the critical importance of obtaining biopsies from metastatic lesions in order to advance our understanding of breast cancer progression and improve the ability to treat – and one day prevents – metastatic disease.
The recently launched second phase of the AURORA-US project is a prospective study to identify molecular targets. It is expected to enroll 200+ patients with recurrent metastatic breast cancer across 19 TBCRC institutions. Visit www.auroraus.org for more information.
About the Breast Cancer Research Foundation Evelyn H. Lauder Founder’s Fund
The Evelyn H. Lauder Founder’s Fund, established in 2013, is dedicated exclusively to addressing the persistent challenges of breast cancer metastasis and has dedicated $31 million to date. Inspired by The Cancer Genome Atlas (TCGA)—which compiled the landmark genomic database of primary tumors—AURORA is building the world’s largest multi-disciplinary repository of matched primary and metastatic tumor data. The AURORA-US and AURORA-EU projects are the centerpiece of the Founder’s Fund. Deep analysis of metastatic tumor DNA, RNA, and proteins are providing new insights into the processes and mechanisms of metastatic cancer. This invaluable resource can be mined to fuel future research and help provide answers to questions we haven’t yet formulated.
About Metastatic Breast Cancer
Metastatic breast cancer (MBC) occurs when breast cancer cells spread to other parts of the body, such as the lungs, brain, liver or bones. Metastatic breast cancer, also referred to as stage IV or advanced breast cancer, is incurable and responsible for virtually all breast cancer related deaths, leading to more than 42,000 deaths in women and men in the U.S. each year.
About the Translational Breast Cancer Research Consortium (TBCRC)
The Translational Breast Cancer Research Consortium (TBCRC) is a collaborative group founded in 2005 to conduct innovative and high-impact clinical trials for breast cancer. The goal of the TBCRC is to conduct innovative, high impact, biologically driven translational and clinical research.