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Published On June 18, 2018

CLINICAL RESEARCH

False Starts

A failed birth control drug gives a boost to cancer treatment.

The success of the first oral contraceptive in 1960 led to both a cultural revolution and a surge in fertility research, as the pharmaceutical giants of the day raced to find better contraceptives. One candidate turned out to be a great success—in treating cancer.

Arthur Walpole ran his laboratory in Manchester, England, at Imperial Chemical Industries (ICI, now part of AstraZeneca). He was briefly commissioned to run drug discovery programs for breast cancer and birth control simultaneously. Walpole believed that estrogen might play a role in each, and looked for compounds that would block the hormone in the body, keeping a special eye out for those that would be mild enough for patients to take regularly.

The company soon shifted its cancer efforts to another division, but Walpole didn’t want to abandon promising research. And studying breast cancer and birth control at the same time had its advantages: It was especially difficult to obtain a legal abortion in Great Britain in the 1960s, which made conducting contraceptive trials, with their risk of unwanted pregnancies, problematic. He could, however, test his drugs for their ability to block estrogen in women with breast cancer. This would serve as an initial step for later contraceptive trials.

In 1969, 46 breast cancer patients at Christie Hospital in Manchester received one of the more promising chemicals—tamoxifen—overseen by oncologist Moya Cole. Patients showed remarkable recoveries, with many tumors receding significantly.

Most breast cancers, it would later be discovered, contain a receptor for estrogen and rely on the hormone to survive. Blocking the estrogen receptor dealt a severe blow to such cells. Cole noted in her review of the trial in 1971 that not only did the drug work, but patients had a “low incidence of troublesome side effects.” This was unheard of at a time when other cancer treatments were highly toxic.

The top brass at ICI were reportedly less than impressed. They reminded researchers that they were supposed to be looking for a birth control drug. The prognosis for breast cancer patients at the time was not good, and the market for such a treatment was not expected even to cover research costs.

When ICI ordered the termination of tamoxifen’s development, Walpole threatened to resign, and ripples of despondency fanned out through the research community. But the company soon reversed its decision, and by 1973 the program was back up and running.

Today, tamoxifen is on the World Health Organization’s list of essential medicines, and the drug has been connected to the survival of more than 400,000 breast cancer patients. A milestone study in 1988, 30 years ago, concluded that tamoxifen could in certain cases be used without traditional chemotherapy—making it the first standalone targeted cancer therapy.

This lesson—that cancer treatments could be tailored to the unique mechanisms of each kind of malignant cell—became one of tamoxifen’s greatest legacies. The insight led to many other targeted treatments and paved the way for an age of personalized cancer medicine.

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