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

One in eight women in the U.S. will develop breast cancer in her lifetime. For 25 to 30 percent of these women, their cancer will spread, or metastasize. While there has been significant progress in early detection and treatment for primary breast cancer, advances in treatment and prevention of metastasis are still needed. As of 2020, an estimated 168,000 individuals in the U.S. alone are living with metastatic breast cancer—and that number is projected to rise.

In 2013, under the direction of our Founding Scientific Director Dr. Larry Norton and former Scientific Advisory Board Chair Dr. Clifford Hudis, BCRF established a dedicated initiative to address the persistent challenges of breast cancer metastasis. This initiative, now known as the Evelyn H. Lauder Founder’s Fund for Metastatic Breast Cancer Research (The Founder’s Fund), was fueled by an outpouring of support honoring the memory and immutable determination of BCRF’s founder, Evelyn H. Lauder, following her death in 2011.

No area in cancer medicine is more pressing and no opportunity more significant than understanding and stopping metastasis. The Founder’s Fund, an international, multi-year collaboration, is the cornerstone of BCRF’s overall investment in metastatic breast cancer, which represents, on average, 40 percent of our annual research grant portfolio. BCRF investigators from around the world are using the most advanced tools of molecular analysis—some developed with BCRF support—to dissect the molecular basis of metastasis in real people in real time. These efforts are yielding new insights into the molecular changes that occur as breast cancer evolves from a localized disease in the breast to one that has spread to one or more vital organs. These discoveries are paving the way to being able to identify aggressive breast cancers before they become lethal and find new targets for treatment and prevention. BCRF has dedicated $41.5 million to this important initiative to date.

The flagship programs of the Founder’s Fund are: AURORA EU, based in Brussels and conducted under the oversight of Dr. Martine Piccart through the Breast International Group (BIG) and AURORA US, coordinated by Dr. Nancy Davidson with clinical aspects being administered by Drs. Antonio Wolff and Ian Krop through the Translational Breast Cancer Research Consortium (TBCRC) based at Johns Hopkins University. The objective of the AURORA programs is to conduct precise, multi-level molecular analyses of breast cancer metastases and the primary tumors they come from to better understand the evolution of metastasis and the mechanisms of drug resistance that allow tumors to grow and spread.

AURORA EU benefits from the collaborative infrastructure of BIG—the world’s largest network of international academic research groups comprised of 55 groups across 70 countries and six continents. The study has recruited more than 1,100 women and men with metastatic breast cancer from 60 hospitals in 11 EU countries. Tumor tissue, blood, serum, and plasma samples are being analyzed to identify genes and gene-outputs driving metastasis, as well as blood-based biomarkers that can be used to non-invasively determine tumor progression and treatment response. These efforts will lead to more efficient clinical trials and better management of metastatic breast cancer. The biospecimens collection will be a valuable resource for continued translational studies.

2019 Update: An early analysis of the first 381 patients out of a planned 1,000 was presented at ESMO Breast Cancer Congress in May 2019. The researchers found genomic alterations in metastatic tumors that may play a role in the spread of cancer and resistance to treatment. Analyses are ongoing, with a planned follow-up involving study participants through 2030.

Read the ESMO 2019 press release here.

2021 Update: The initial results presented as ESMO in 2019 were published in the journal Cancer Discovery in 2021. Notable findings include:

• 30 percent of metastatic tumors, particularly those arising from triple-negative breast cancer (TNBC), had a distinctive DNA repair deficiency.
• Subtype switching from less aggressive (Luminal A) disease in the primary breast cancer to more aggressive disease in the metastatic tumor occurred in about one-third of cases.
• Two novel biomarkers were identified that are associated with very poor prognosis.
• Metastatic tumors lost gene signatures related to anti-tumor immunity.
• Targeted therapies exist for 50 percent of patients who were found to have certain tumor genomic aberrations.

Read more about the 2021 findings here.

Ongoing Studies: Multi-plex molecular tumor analysis of the full AURORA EU cohort continues. A sub-study of invasive lobular and metastatic TNBC, as well as very late recurrences of MBC, is underway.

AURORA US harnesses the extensive clinical trial infrastructure of TBCRC, a model clinical trials program accelerating advances in breast cancer care. TBCRC is comprised of 18 clinical sites and more than 100 participating investigators conducting trials that integrate clinical and laboratory studies. The leadership of AURORA US includes a steering committee (Drs. Nancy Davidson, Larry Norton, Charles Perou, Sue Hilsenbeck, Lisa Carey, and Antonio Wolff) and several working groups (WG) led by Drs. W. Fraser Symmans and Andrea Richardson (Pathology WG); Charles Perou and Elaine Mardis (Molecular WG); and Tari King and Minetta Liu (Clinical WG). Shirley Mertz and Patty Spears head the patient advocate WG.

The AURORA US study has two components: a retrospective analysis of primary and metastatic tumors and a prospective clinical trial. The first report from the retrospective phase of the study involved archived tissue samples from the primary tumor and at least one distant metastasis.

2019 Update: In total, samples from 55 patients, including 102 distinct metastatic lesions, were subject to multiple DNA and gene expression genomic analyses. Reporting at the San Antonio Breast Cancer Symposium, researchers identified molecular alterations—unique to each breast cancer subtype—in the metastatic tumor when compared to the matched primary breast cancer. As reported by AURORA EU, the retrospective analysis from AURORA US noted what they called “subtype switching” in about half of luminal-like breast cancers, whereby they shifted to more aggressive MBC cancers. The researchers also saw differences in genes involved in the tumor microenvironment and immune regulation in MBC lesions compared to the primary breast cancer, with an overall decrease in immune activation in the metastases compared to the primary. A manuscript is in final preparation for publication.

Read the 2019 SABCS press release here.

2021 Update: The prospective clinical trial, which launched in early 2020 will enroll at least 200 patients. Enrollment was delayed due to the COVID-19 precautions, but as of spring 2021, 64 patients had enrolled. For more information on the study and locations visit www.auroraus.org.

2022 Update: AURORA US investigators published their findings in the prestigious journal Nature Cancer in December. They demonstrated that immune cells are lower in metastases, changes in DNA enable metastasis to proceed, and the tumor microenvironment plays a vital role in the metastatic process. Investigators also detailed the subtype switching that occurs in metastasis.

The prospective clinical trial continues to recruit participants and confirm these findings in a larger cohort of patients—and the information gleaned from this study may help to guide personalized treatment decisions for patients with MBC.

Read more about their findings here.