Fueling the search for a cure

In 1994, Gabriel Hortobagyi, M.D., was selected as the first MD Anderson investigator to receive a Breast Cancer Research Foundation (BCRF) research grant. Since then, the nonprofit organization committed to preventing breast cancer and finding a cure has designated approximately $24 million for breast cancer research at MD Anderson.

BCRF’s impact on the fight against breast cancer has been enormous, says Hortobagyi, who retired as chair of Breast Medical Oncology at MD Anderson in 2015 and currently chairs BCRF’s Scientific Advisory Board.

“Over the past 25 years, BCRF has provided funding for several innovative research programs at MD Anderson, giving investigators the freedom to undertake some risks and thus accelerate the rate of progress,” he says. “BCRF funds have provided stability to our research teams — continuity of research funding and leverage to obtain larger peer-reviewed grants based on preliminary research results. We couldn’t have done it without BCRF.”

BCRF, founded in 1993, was the brainchild of cosmetics executive and breast cancer survivor Evelyn Lauder and oncologist Larry Norton, M.D., now BCRF co-scientific director. Their vision was to change the landscape of breast cancer research, which at the time offered little hope for patients and their loved ones.

Lauder died of ovarian cancer in 2011, but her determination and can-do spirit, reflected in the pink ribbon campaign she spearheaded with Self magazine editor Alexandra Penney, continue to inspire BCRF’s mission. The foundation’s primary focus has always been research, and today BCRF is the nation’s highest-rated breast cancer organization and the largest provider of funds for breast cancer research in the world.

Grant applications are by invitation only, upon the approval of BCRF’s Scientific Advisory Board. For the 2019-20 grant-funding cycle, BCRF has committed $66 million to nearly 275 breast cancer researchers in 14 countries studying tumor biology, cancer genetics, prevention, treatment, metastasis and survivorship.

“What’s particularly unique about BCRF is its funding model,” says Dorraya El-Ashry, Ph.D., BCRF chief scientific officer. “We’re funding people, not projects — giving investigators the freedom to pursue their most promising ideas, yielding unexpected breakthroughs.”

Before joining BCRF in May, El-Ashry had an accomplished career in breast cancer research. She has received numerous BCRF grants over the years for her own research, focusing on mechanisms of estrogen-receptor-negative breast cancer. Personal losses of friends, colleagues and family members to breast cancer, combined with current survival statistics and gaps in federal research funding, have been the “inspiration and impetus” for El-Ashry’s continued commitment to finding a cure. To that end, she is working with BCRF’s Scientific Advisory Board to identify crucial areas of focus and find the best new investigators with a passion to pursue promising ideas.

“As part of our process, we seek the best and brightest scientists to work on the most urgent needs,” says El-Ashry. “We are, undoubtedly, on the path toward ending breast cancer as a life-threatening disease. We believe the incredible researchers at MD Anderson will surely help us achieve our mission.”

Thanks to BCRF funding, more than a dozen MD Anderson researchers have pursued innovative ways to detect, treat and prevent the disease more effectively. Among them are Naoto T. Ueno, M.D., Ph.D., professor of Breast Medical Oncology; Xiaoping Wang, Ph.D., assistant professor of Breast Medical Oncology-Research; Sharon Giordano, M.D., chair of Health Services Clinical Research; and Zhen Fan, M.D., professor of Experimental Therapeutics.

Ueno and Wang are investigating potential new therapies for inflammatory breast cancer (IBC), a rare and aggressive type of breast cancer. Before BCRF funding, Ueno says, his team lacked an animal model for studying the environment surrounding the tumor, or tumor microenvironment. BCRF support enabled them to engraft IBC cells into a humanized mouse to create the first immunocompetent IBC mouse model in the world.

“Using this novel humanized IBC mouse model, our group is studying the immune impact of the anti-epidermal growth factor receptor (EGFR) pathway by using panitumumab, a drug that targets this pathway,” says Ueno. “We have demonstrated that panitumumab reduces IBC tumor growth by inducing immune responses, including an increase of cytotoxic T cells and decrease of regulatory T-cell infiltration. These are the first findings of immune responses induced by targeted therapy in IBC. This exciting mechanistic data will lead to a novel clinical trial of immunotherapy combined with targeting EGFR in IBC.”

Giordano works with the Male Breast Cancer International Program, a worldwide effort to better characterize the biology of the disease, develop more effective treatments and improve outcomes for men with breast cancer. “This program can only exist due to BCRF’s continuous and crucial support,” she says.

The overall goal is to launch therapeutic clinical trials focusing on breast cancer in men. Part 1 is a retrospective joint analysis of clinical data and tumor samples from more than 1,800 male breast cancer cases in 23 centers from nine countries over the last 20 years. Part 2 is a prospective registry of all patients treated in the program’s global network for a period of two years, with prospective collection of biological material. Part 3 is a prospective clinical trial, evaluating a new target agent to treat this disease.

“These recent efforts provide evidence that clinical trials of treatments for breast cancer in men are feasible, and a continued commitment to such studies will be essential to improve the standard of care for men with breast cancer,” says Giordano.

Fan’s BCRF-funded project seeks to help fulfill the dream of using vaccines to prevent or treat cancer. He and his team are working to develop a therapeutic approach that alters cancer cells so they can be recognized and destroyed by the body’s immune system. The strategy is to trick the human immune system to recognize cancer cells as flu virus-infected cells and launch an immune response against them by reawakening immune cells developed through previous natural flu infection or through vaccination against the virus during childhood.

BCRF funding provides critical support for Fan’s team to develop two key technical components: an antibody-based drug delivery vehicle for delivering flu virus-related peptides to targeted breast tumors and animal models for testing whether the strategy can prolong the survival of mice with metastatic breast tumors.

“This research to redirect pre-existing infectious disease-related noncancer immunity to fight cancer is a high-risk but potentially high-impact project,” says Fan. “Without BCRF’s support, my team could not have achieved the progress so far to test this strategy in preclinical breast tumor models.”