Angela Brodie
Pharmacologist who developed new drugs for breast cancer
ANGELA BRODIE, who has died aged 82, was a British-born pharmacologist who discovered the effectiveness of aromatase inhibitors as a treatment for oestrogen-positive breast cancer.
She became interested in treatments for breast cancer in the late 1950s when working as a graduate researcher at Manchester’s Christie Cancer Hospital. “There was very little known, and they did horrible things to you, a lot surgically,” she recalled. “I did feel there should be a better way of doing things.”
About 70 per cent of all breast cancers are linked to the hormone oestrogen. It was another scientist, Craig Jordan, who discovered the properties of tamoxifen, which prevents oestrogen from binding to cancer cell receptors. But Angela Brodie was concerned that, as tamoxifen also serves as a weak oestrogen, it might not block tumours effectively enough. Other scientists cited evidence that it put women at increased risk for endometrial cancer and stroke.
Rather than searching for a drug that would block oestrogen, Angela Brodie looked for a way to limit its production. Her husband Harry, a chemist involved in researching contraceptives, had synthesised the first aromatase inhibitors – compounds which prevent the creation of an enzyme vital to producing oestrogen. While they did not prove effective enough as contraceptives in animal trials, Angela suggested that they might be effective against breast cancer.
At the University of Maryland, Angela Brodie focused on 4-OHA, which had proved one of the most effective compounds in limiting oestrogen formation. By the end of the 1970s, after tests on animals, she was searching for an opportunity to subject it to human clinical trials.
In 1980 her work caught the attention of Charles Coombes, an oncologist at the Royal Marsden Hospital. In 1982 Coombes gave 4-OHA to 11 women whose tumours were resistant to standard therapies, with four seeing a dramatic improvement. Further trials demonstrated that aromatase inhibitors were not only more effective than tamoxifen at preventing a recurrence of breast cancer but also freer of side effects.
Marketed as formestane, 4-OHA was released for worldwide use in 1994, paving the way for the development of other aromatase inhibitors with fewer side-effects – among them, anastrozole, letrozole and exemestane – which are now used worldwide. “It was a little bit of an uphill battle,” Angela Brodie recalled. “But I was always sure we were right.”
Angela Mary Hartley was born in Oldham, Lancashire, on September 28 1934, and grew up mostly in Buxton. Her father, Herbert Hartley, had helped to develop the industry for polyurethanes, and during the Second World War would design an anti-tank grenade that stuck to the tanks instead of bouncing off them.
He inspired her interest in science, and after education at a Quaker boarding school she read Biochemistry at Sheffield University and took a doctorate at Manchester University.
During her time at the Christie Cancer Hospital, she won a fellowship to train at the Worcester Foundation, now part of the University of Massachusetts medical school. There she met and married Harry Brodie, with whom she had two sons and with whom she collaborated for many years.
She became an associate professor, and later professor, of Pharmacology at the University of Maryland medical school, retiring in 2016. In later years she expanded her research into prostate cancer. In 2005 she became the first woman to win the $250,000 Charles F Kettering Prize, an honour that recognises “the most outstanding recent contribution to the diagnosis or treatment of cancer”.
She is survived by her husband and a son. Her other son died in 2006.
Angela Brodie, born September 28 1934, died June 7 2017