Angela Hartley BrodieSeptember 28, 1934 ~ June 7, 2017 (age 82)
Angela Brodie, an English-born scientist whose seminal research into a compound that blocks estrogen production helped generate a new class of drugs to treat breast cancer and was credited with saving thousands of lives, died June 7 at her home in Fulton, Md. She was 82.
The University of Maryland School of Medicine, where she was a professor emeritus of pharmacology and experimental therapeutics, announced the death and said the cause was complications from Parkinson’s disease.
Her hormone-therapy regimen, which involved a drug compound known as aromatase inhibitors, met with skepticism during its experimental stages in the 1970s and 1980s but is now a standard treatment offered to treat postmenopausal women with advanced or metastatic breast cancer.
“Her work was about as important as any single person’s could be in drug development for cancer,” said Clifford A. Hudis, the longtime chief of breast cancer medicine service at Memorial Sloan Kettering Cancer Center in New York and now chief executive of the American Society of Clinical Oncology. “She provided a safe, ultimately inexpensive and widely available treatment with limited toxicity and that is used all over the world.”
Aromatase inhibitors prevent the creation of aromatase, an enzyme vital to producing the hormone estrogen, which can fuel tumor growth in breast tissue. Dr. Brodie’s efforts culminated in the second generation of hormone therapies to combat breast cancer, after earlier drugs such as tamoxifen.
Dr. Angela Brodie (University of Maryland School of Medicine)
“There was meaningful improvement,” Hudis said. “They were a little safer and more effective. When you apply ‘a little safer and more effective’ to millions of people around the globe, it makes a big difference.”
The presence of tumors in the body were widely considered a death sentence for women when Dr. Brodie began her career as a research assistant at a British cancer hospital in the early 1960s. The treatment possibilities included chemotherapy, with its toxic side effects, or radically invasive surgery to remove ovaries and other hormone glands.
“There was very little known, and they did horrible things to you, a lot surgically,” Dr. Brodie later told the San Antonio Express-News. “I did feel there should be a better way of doing things.”
Dr. Brodie’s formative years as a researcher were spent at the Worcester Foundation for Experimental Biology in Shrewsbury, Mass., which was known for its pioneering work on oral contraceptives. Her husband, Harry Brodie, a chemist, had synthesized the first aromatase inhibitors as part of his research into contraceptives.
“But that didn’t turn out well,” Harry Brodie said in an interview. “With contraception, they really have to be 100 percent effective, and I could never achieve 100 percent with my animal studies.”
He said his wife, a senior scientist in the lab, suggested that the hormone-blocking compound be repurposed as a way to treat breast cancer. “You didn’t have to be 100 percent perfect with breast cancer,” he added, “just effective.”
At the time, cancer researchers were encouraged by the new drug tamoxifen, which prevents estrogen from binding to cancer cell receptors.
Angela Brodie later told The Washington Post she was doubtful about how effectively tamoxifen — itself a weak estrogen — could fight the growth of tumors. In addition, research had shown that tamoxifen had a higher risk of causing endometrial cancer and strokes for some patients.
Dr. Brodie sought to use one of her husband’s most effective steroidal aromatase inhibitors — 4-hydroxyandrostenedione (4-OHA) — to limit estrogen formation in the first place, rather than using tamoxifen to block it.
Their research, which spanned much of the 1970s, provided reams of data on 4-OHA in animals, but they were unable to obtain grant money to conduct clinical trials on humans.
In 1979, Harry Brodie left for an administrative post at the National Institutes of Health, while Angela Brodie joined U-Md. to continue research on 4-OHA. Her findings — published in medical journals and presented at conferences — intrigued Charles Coombes, a British oncologist.
At her Baltimore lab, she produced small batches of 4-OHA and sent it to Coombes in London. Facing fewer bureaucratic hurdles, he began conducting clinical trials on women and reported promising results.
Their combined efforts led the Swiss drugmaker Ciba-Geigy to produce the drug in Europe and later in the United States. The drug, under the name formestane, was heralded as a way to help postmenopausal women — those most susceptible to the disease and whose tumors are most likely to have to higher estrogen receptor levels — have a better quality of life, in some circumstances allowing chemo to be delayed.
The drugs were not popular at first, Hudis said, because they caused broad endocrine suppression, leading to a variety of medical complications. But later breakthroughs with a new breed of selective aromatase inhibitors — among them, anastrozole, letrozole and exemestane — have made the compounds safer, better tolerated and useful.
“Now the inhibitors are the drug of choice for post-menopausal women in advanced cancer and even in early stage cancer,” he said.
Angela Mary Hartley was born in Oldham, near Manchester, England, on Sept. 28, 1934, and grew up mostly in Buxton. Her father, an industrial chemist, had been an expert in glues and helped develop for the British military an anti-tank hand grenade that stuck to the armored vehicles instead of bouncing off them.
After attending a Quaker boarding school, Dr. Brodie graduated in 1956 from the University of Sheffield with a bachelor’s degree in biochemistry and received a doctorate in 1961 from the University of Manchester in chemical pathology.
An early job as a research assistant at a cancer hospital in Manchester influenced the direction of her career. She won an NIH-sponsored post-doctoral training fellowship that brought her to the Worcester Foundation, now part of the University of Massachusetts medical school.
Beside her husband of 52 years, a retired NIH executive secretary for grant review, survivors include a son, Mark Brodie of La Crescenta, Calif.; a brother; and two grandchildren. Another son, John H. Brodie, died in 2006.
Dr. Brodie, who retired from U.-Md. in 2016, wrote more than 200 scientific papers and served as an editor of several journals. She had spent the final years of her career conducting research with a colleague, Vincent C.O. Njar, into the use of aromatase inhibitors to treat prostate cancer. That remains at the clinical trial phase.
Dr. Brodie collected a storm of honors over the last two decades, including the 2005 Charles F. Kettering Prize, sponsored by the General Motors Cancer Research Foundation for most outstanding contribution to the diagnosis or treatment of cancer; she was the first woman to win the now-discontinued award, which came with a check for $250,000.
To aspiring scientists, she often recalled the 15 years of research she conducted in relative anonymity on aromatase inhibitors. “If you have something you think is a good idea, stick to it,” she said in 2006.
“You have to do something that is going to benefit mankind.”
Drs. Angela and Harry Brodie Distinguished Professorship in Translational Cancer Research”