In the 1970s, only 40% of women diagnosed with breast cancer could expect to survive for 10 years or more. Today the figure is more than 75%. Screening and early diagnosis have played a role, but one of the main reasons for the improvement is the drug tamoxifen, which significantly reduces the risk of cancer recurrence after surgery.
British-American pharmacologist Craig Jordan, who has died aged 76, was the first to show that tamoxifen could stop tumors from growing by stopping the female hormone estrogen from attaching to cells in the breast at specific sites that have estrogen receptors named.
Breast cancer is the most common cancer among women around the world and 80% of women with the disease have receptors that make them sensitive to estrogen, which can stimulate cells in the breast to reproduce uncontrollably and form tumors.
Jordan’s lifelong study of tamoxifen led to the discovery of a series of other effective treatments for breast cancer that either blocked estrogen receptors or reduced the amount of hormone the body produced. 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 great skepticism from the medical community. He was not a medical doctor but a laboratory scientist who did his research on rats and mice. Tamoxifen does not kill cancer cells, it simply stops them from growing. The wisdom he received in the 70s when he started 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 tumor . Such treatments, although they can be effective, are distressing for patients and have many side effects.
“There was an obsession with the idea that those 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 while saying no, target the [o]estrogen receptor and give tamoxifen forever and people will live.”
It took decades before the evidence for tamoxifen’s effectiveness became undeniable. A number of clinical research groups, encouraged by Jordan’s laboratory results, tested tamoxifen in patients, but the results, while encouraging, were too marginal to change practice.
In 1998 the early breast Cancer Triallists Collaborative Group, based in Oxford, combined data from studies of 37,000 women to show that those with estrogen-sensitive tumors who took tamoxifen for five years after surgery had a 47% reduction in the risk of the cancer experienced its return and a 26% reduction. at risk of dying within 10 years.
Tamoxifen and other selective estrogen receptor modulators are now part of the standard treatment for women who have undergone surgery for estrogen-sensitive breast cancer.
Jordan’s mother, Cynthia Mottram, was a GI bride who met his father, Virgil Johnson, when he was serving as a soldier in the US Army in Britain during World War II. They returned to New Braunfels, Texas, where Jordan was born, but the marriage broke up 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 up chemistry with such enthusiasm that his mother had him set up a laboratory at home (which led to the kinds of near-disasters that characterized the early lives of many successful scientists has). After his mother remarried, Craig was adopted by his stepfather, Geoffrey Jordan, and took his name.
At first, his ambition was to work as a technician nearby ICI laboratories, but he successfully gained a place at the University of Leeds to study pharmacology. Taking a summer job at ICI, he met endocrinologist Arthur Walpole, who was 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 estrogen receptors.
In 1972, Jordan went to the Worcester Foundation for Experimental Biology in Massachusetts. The lab focused on contraception, but since ICI 46,474 failed as a contraceptive, Jordan began investigating its effects on breast cancer in rats. Meanwhile, in 1973, ICI gave the drug a name, tamoxifen, and introduced 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 work with ICI. His key discoveries in this period were that tamoxifen, given over a period of years, could be used to prevent cancer from returning after surgery; and that it can prevent cancer from developing in women whose biology puts 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 posts at a succession of leading research universities, setting up a “tamoxifen team” at each, before finally becoming professor and chair in 2014 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 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 joined the Officers’ Training Corps while a student at Leeds, combining his PhD research with terms in the army in Germany during the Cold War. He was further 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 has received many honors over the course of his career and in 2019 was appointed CMG in the Queen’s Birthday Honors for services to women’s health. In turn, he funded prizes, scholarships and special lectures at the universities of Leeds and Oxford, aware of the debt he owed to British society for his early teaching and research opportunities. He was open about his diagnosis with kidney cancer in 2018 and continued to work 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.
