In the 1970s only 40% of women diagnosed with breast cancer could expect to survive for 10 years or more. Today that figure is over 75%. Screening and early diagnosis have played a part, but one of the key reasons for the improvement is the drug tamoxifen, which massively reduces the risk of cancer recurring after surgery.
The British-American pharmacologist Craig Jordan, who has died aged 76, was the first to show that tamoxifen could stop tumours growing by blocking the female hormone oestrogen from locking on to cells in the breast at specific sites called oestrogen receptors.
Breast cancer is the commonest cancer in women across the world and 80% of women with the disease have receptors that make them sensitive to oestrogen, which can stimulate cells in the breast to reproduce uncontrollably and form tumours.
Jordan’s lifelong study of tamoxifen led to the discovery of a range of other effective treatments for breast cancer that either blocked oestrogen receptors or reduced the amount of the hormone the body produces. His studies have also improved women’s health by shedding light on other conditions including endometrial cancer, osteoporosis and menopausal symptoms.
He made his discoveries in the face of huge scepticism from the medical community. He was not a medical doctor but a laboratory scientist who conducted his research on rats and mice. Tamoxifen does not kill cancer cells, it simply stops them from growing. The received wisdom in the 70s when he began his work was that the only way to deal with cancer was to cut it out, or blast it with radiation or powerful chemicals to destroy every trace of the tumour. Such treatments, though they can be effective, are distressing for patients and have many side effects.
“There was an obsession with the idea that that combination chemotherapies were going to cure all cancers,” Jordan told the website Oncology Central in 2019. “It felt like we were trying to swim upstream as we were saying no, target the [o]estrogen receptor and give tamoxifen forever and people will stay alive.”
It took decades before the evidence for tamoxifen’s effectiveness became undeniable. A number of clinical research groups, encouraged by Jordan’s laboratory results, had tested tamoxifen in patients, but the results, though encouraging, were too marginal to change practice.
In 1998 the Early Breast Cancer Triallists Collaborative Group, based in Oxford, combined the data from studies of 37,000 women to show that those with oestrogen-sensitive tumours who took tamoxifen for five years after surgery experienced a 47% reduction in the risk of the cancer returning and a 26% reduction in the risk of dying within 10 years.
Tamoxifen and other selective oestrogen receptor modulators are now part of the standard treatment for women who have had surgery for oestrogen-sensitive breast cancers.
Jordan’s mother, Cynthia Mottram, was a GI bride who met his father, Virgil Johnson, when he was in service as a soldier with the US army in Britain during the second world war. They returned to New Braunfels in Texas, where Jordan was born, but the marriage broke down and she brought her son back to her home in Cheshire when he was a toddler.
He attended Moseley Hall grammar school in Cheadle, where he took to chemistry with such enthusiasm that his mother let him set up a laboratory at home (leading to the kinds of near-disaster that punctuate the early lives of many successful scientists). After his mother remarried, Craig was adopted by his stepfather, Geoffrey Jordan, and took his name.
At first his ambition did not reach beyond working as a technician at the nearby ICI laboratories, but he successfully obtained a place at the University of Leeds to study pharmacology. Taking a summer job with ICI, he met the endocrinologist Arthur Walpole, who had been part of the team that developed tamoxifen, then known as ICI 46,474.
It was supposed to be a contraceptive, but early trials led to more pregnancies, rather than fewer. During his PhD at Leeds, Jordan developed strong links with the ICI scientists, who funded the early stages of his work on oestrogen receptors.
In 1972 Jordan went to the Worcester Foundation for Experimental Biology in Massachusetts. The lab focused on contraception, but as ICI 46,474 had failed as a contraceptive Jordan began to examine its effects on breast cancer in rats. Meanwhile, in 1973, ICI had given the drug a name, tamoxifen, and launched it as a not particularly effective treatment for late-stage breast cancer.
The following year Jordan returned to Leeds as a lecturer, where he continued to collaborate with ICI. His key discoveries in this period were that given over a period of years, tamoxifen could be used to prevent cancer coming back after surgery; and that it could prevent cancer developing in women whose biology put them at particularly high risk. He also discovered a very effective breakdown product of tamoxifen that went on to form the basis of other drugs that prevent postmenopausal women from losing bone density.
In 1980 he moved permanently to the US, where he held senior positions at a succession of leading research universities, setting up a “tamoxifen team” at each, before finally settling in 2014 as a professor and chair of cancer research at the University of Texas MD Anderson Cancer Center in Houston. His further discoveries included a small increased risk of endometrial cancer with tamoxifen, so that doctors now screen their patients before prescribing the drug.
For much of his life, Jordan had an unusual parallel career as an adviser on biological and chemical weapons – and illicit drug use – to the British and US armies.
His family had a strong military heritage and he had joined the Officers’ Training Corps while a student at Leeds, combining his PhD research with stints with the army in Germany during the cold war. He went on to be recruited into the intelligence corps with the rank of captain, and subsequently became a member of the SAS reserve. He was an avid collector of antique weapons, and described himself as an “outstanding shot”.
He received many honours in the course of his career, and was appointed CMG in the Queen’s birthday honours in 2019 for services to women’s health. In turn he funded prizes, scholarships and special lectures at the universities of Leeds and Oxford, conscious of the debt he owed to British society for his early education and research opportunities. He was open about his diagnosis with kidney cancer in 2018 and continued working until shortly before his death.
Craig Jordan was married three times, each marriage ending in divorce. He is survived by Alexandra and Helen, his daughters from his first marriage, to Marion Williams, and five grandchildren.
• Virgil Craig Jordan, pharmacologist, born 25 July 1947; died 9 June 2024
